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Background. Colon cancer is the second most common malignancy causing the majority of cancer-related deaths. B7-H3 concentrations have drawn major interest as possible diagnostic biomarkers of cancer. The aim of this study was to measure the preoperative serum B7-H3 levels and to determine those that are replaced in colon cancer. Method. We measured preoperative serum B7-H3 concentrations of 90 patients aged 57-69 years diagnosed with colon cancer and 50 age-matched healthy individuals. B7-H3 levels were determined using the sandwich enzyme-linked immunosorbent assay (ELISA). Patients were categorized by stage based on the TNM staging system, and the serum levels of B7-H3 were compared between patients with different TNM stages. Result. No statistically significant difference was found between the patient and control groups in terms of age and gender. Preoperative serum B7-H3 levels were statistically significantly higher in patients with colon cancer than in the healthy group (p < 0.001). Preoperative serum B7-H3 concentration of the stage IV patients was significantly higher than those of the patients with stage I and stage II disease. In addition, higher serum B7-H3 levels were associated with lymph node status and distant metastasis in colon cancer. Conclusion. We showed that B7-H3 is highly expressed in colon cancer and can be used as a candidate diagnostic biomarker and a potential target in colon cancer in future. [ABSTRACT FROM AUTHOR]

Background. Tumor angiogenesis plays a vital role in tumorigenesis, proliferation, and metastasis. Recently, vascular endothelial growth factor A (VEGFA) and CXC chemokines have been shown to play vital roles in angiogenesis. Exploring the expression level, gene regulatory network, prognostic value, and target prediction of the CXC chemokine-VEGFA network in colon adenocarcinoma (COAD) is crucial from the perspective of tumor angiogenesis. Methods. In this study, we analyzed gene expression and regulation, prognostic value, target prediction, and immune infiltrates related to the CXC chemokine-VEGFA network in patients with COAD using multiple databases (cBioPortal, UALCAN, Human Protein Atlas, GeneMANIA, GEPIA, TIMER (version 2.0), TRRUST (version 2), LinkedOmics, and Metascape). Results. Our results showed that CXCL1/2/3/5/6/8/11/16/17 and VEGFA were markedly overexpressed, while CXCL12/13/14 were underexpressed in patients with COAD. Moreover, genetic alterations in the CXC chemokine-VEGFA network found at varying rates in patients with COAD were as follows: CXCL1/2/17 (2.1%), CXCL3/16 (2.6%), CXCL5/14 (2.4%), CXCL6 (3%), CXCL8 (0.8%), CXCL11/13 (1.9%), CXCL12 (0.6%), and VEGFA (1.3%). Promoter methylation of CXCL1/2/3/11/13/17 was considerably lower in patients with COAD, whereas methylation of CXCL5/6/12/14 and VEGFA was considerably higher. Furthermore, CXCL9/10/11 and VEGFA expression was notably correlated with the pathological stages of COAD. In addition, patients with COAD with high CXCL8/11/14 or low VEGFA expression levels survived longer than patients with dissimilar expression levels. CXC chemokines and VEGFA form a complex regulatory network through coexpression, colocalization, and genetic interactions. Moreover, many transcription factor targets of the CXC chemokine-VEGFA network in patients with COAD were identified: RELA, NFKB1, ZFP36, XBP1, HDAC2, SP1, ATF4, EP300, BRCA1, ESR1, HIF1A, EGR1, STAT3, and JUN. We further identified the top three miRNAs involved in regulating each CXC chemokine within the network: miR-518C, miR-369-3P, and miR-448 regulated CXCL1; miR-518C, miR-218, and miR-493 regulated CXCL2; miR-448, miR-369-3P, and miR-221 regulated CXCL3; miR-423 regulated CXCL13; miR-378, miR-381, and miR-210 regulated CXCL14; miR-369-3P, miR-382, and miR-208 regulated CXCL17; miR-486 and miR-199A regulated VEGFA. Furthermore, the CXC chemokine-VEGFA network in patients with COAD was notably associated with immune infiltration. Conclusions. This study revealed that the CXC chemokine-VEGFA network might act as a prognostic biomarker for patients with COAD. Moreover, our study provides new therapeutic targets for COAD, serving as a reference for further research in the future. [ABSTRACT FROM AUTHOR]

Aims. The purpose of this study was to investigate the correlation of INSC gene with the level of immune infiltration and clinical prognosis in colon adenocarcinoma (COAD) patients. Materials and Methods. INSC expression profile data and clinicopathological information of COAD patients were downloaded from TCGA. Xiantao bioinformatics tool was used to analyze the expression of INSC between the COAD group and the normal control group, and GEPIA2 was used to analyze the top 100 coexpressed genes. Logistic regression analysis was performed to assess the relationship between clinicopathological features and INSC. The Kaplan-Meier method and Cox regression model were used to perform the survival analysis. CIBERSORT algorithm was used to analyze the relationship between INSC expression and immune infiltration cells. Results. The expression level of INSC in COAD was significantly downregulated. The result of logistic regression analysis confirmed that tumor stage was the final influencing factor of INSC expression. The overall survival rate of INSC in the high expression group was higher than that of the low expression group, and it was an independent risk factor of prognosis. Enrichment results indicated that INSC was enriched in the regulation of T-helper 2 cell differentiation pathway. Immune infiltration analysis showed that INSC expression was positively correlated with the B cell plasma, T cell CD4+ memory resting, activated myeloid dendritic cells, and eosinophils. Conclusions. Our study found that the expression of INSC was significantly downregulated in COAD, which regulated immune-infiltrating cells during cancer development and was associated with malignant progression in COAD patients. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate the mechanism of action of Disulfiram against colon cancer through a network pharmacology approach. The targets were then imported into the Cytoscape 3.7.2 software to construct a network of active ingredient targets and were imported into the STRING database to construct a protein-protein interaction (PPI) network, and the Bisogenet plug-in in Cytoscape 3.7.2 was used for network topology analysis. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the potential targets of Yiqi and Baiyu Tang for colon cancer using the R-language Bioconductor platform, and the results were imported into Cytoscape 3.7.2 to obtain KEGG network relationship maps. Molecular docking software Autodock Vina was used to map the core targets to the active ingredients. A total of 119 chemical components and 694 disease targets were obtained, including 113 intersecting targets. The key targets included AKT1 and TP53, and GO functional analysis mainly related to ubiquitination and apoptosis, etc. KEGG analysis showed that the treatment of colon cancer with Ganchenzan mainly acted through cancer-related signaling pathways such as AGE-RAGE and P13K-Akt, and the molecular docking results showed the best binding performance with TP53. [ABSTRACT FROM AUTHOR]

In recent years, people's living standards are getting higher and higher, and life pressure is also increasing, and there are also many problems in eating habits. This is also the direct cause of colon cancer. The aim of this paper was to investigate whether anesthetic drugs could positively affect the proliferation and apoptosis of colon cancer cells. In this paper, the significance of anesthetic drugs is proposed, and an artificial neural network algorithm based on artificial intelligence is proposed. It is well known that artificial neural networks play an important role in medicine. The experimental results of this paper show that the incidence of colon cancer in 2020 will be in the range of 5%-35%, and the incidence of colon cancer in 2021 will be in the range of 7%-30%. While colon cancer rates in 2021 do not appear to be as high as colon cancer rates in 2020, they are generally much higher than colon cancer rates in 2020. It can be seen that as the population ages, the number of colon cancer patients is increasing due to the lack of emphasis on health. This also means that the incidence of colon cancer is getting higher and higher, and traditional drug chemotherapy has been unable to play a good role in inhibiting the proliferation of colon cancer cells. Therefore, this paper investigated the effects of anesthetic drugs on the proliferation and apoptosis of human colon cancer cells. [ABSTRACT FROM AUTHOR]

Cancer-testis (CT) genes are typically expressed in the testes; however, they have been linked to aberrant expression in a variety of malignancies. MAGE-B family genes are an example of CT genes. Therefore, the overarching objective of this study was to examine the expressions of MAGE-B family genes in several patients with colon cancer (CC) to see if they might be employed as cancer biomarkers in the early phases of cancer detection and to improve treatment. In this investigation, RT-PCR was used to analyze MAGE-B family genes in neighboring normal colon (NC) tissue from 10 CC patients. In addition, the effect of DNA demethylation on the expression status of the MAGE-B1 gene was evaluated by RT-PCR in HCT116 and Caco-2 cells and by qRT-PCR for HCT116 only after treating both CC cell lines with varying concentrations of 5-aza-2 ' -deoxycytidine (1.0, 5.0, and 10.0 μM) for 48 or 72 hours. All MAGE-B family genes except for MAGE-B1 showed weak bands in several samples of NC tissues: MAGE-B2, MAGE-B3, MAGE-B4, MAGE-B5, and MAGE-B6 genes were observed in 40%, 50%, 40%, 30%, and 60% of the NC samples, respectively. Nonetheless, they had strong bands in multiple samples of CC tissues, with 70%, 90%, 60%, 50%, and 90% of the CC samples, respectively. Interestingly, MAGE-B1 was detected in 60% of CC tissues but not in NC tissues, suggesting that it is a potential biomarker for early CC detection. MAGE-B1 expression was not observed in either untreated or DMSO-treated HCT116 cells after 48 or 72 hours of treatment. However, according to the RT-PCR and qRT-PCR results, the MAGE-B1 gene was overexpressed in the HCT116 cells treated with three different concentrations of 5-aza-2 ' -deoxycytidine. This shows that demethylation plays a crucial role in MAGE-B1 expression activation. [ABSTRACT FROM AUTHOR]

Noncoding RNA (ncRNA) is a kind of RNA that plays a key role in a variety of biological processes, illnesses, and tumours despite the fact that it cannot be translated into proteins. The HT29 colon cancer cell line was utilized to create a 5-FU drug-resistant cell strain (control group), a lentivirus SNHG20 carrier (OE-SNHG20 group), and an SNHG20 shRNA carrier (SNHG20 shRNA carrier group) (SE-SNHG20 group). To determine the expression of cell SNHG20, a real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized, and cholecystokinin-octapeptide (CCK-8) was used to detect the difference in 5-FU inhibitory concentration 50. The goal of the study was to see how variations in long nonencoding ribonucleic acid (lncRNA) SNHG20 expression affect colon cancer cell 5-fluorouracil (5-FU) chemotherapeutic sensitivity by collecting colon cancer and normal para cancer tissues and analysing the differences in SNHG20 expression. The ability of cell cladogenesis was tested using platform cladogenesis. Cell apoptosis was detected using flow cytometry. Western blots revealed the presence of protein phosphatidylinositol kinase (PI3K), protein kinase B (AKT), caspase-3, e-cadherin, and matrix metalloproteinase 9 (MMP-9) enzymes. The findings revealed that SNHG20 expression was considerably upregulated (P < 0.05) in colon cancer tissue and 5-FU drug-resistant colon cancer cells. Cell 5-FU IC50, cell cladogenesis, cell survival rate, and MMP-9, P-PI3K, and P-AKT expression were all significantly improved. Cell apoptosis and expressions of E-cadherin and caspase-3, on the other hand, were considerably decreased (P < 0.05). Cell 5-FU IC50, cell cladogenesis, cell survival rate, and the expressions of MMP-9, P-PI3K, and P-AKT were all significantly lower in the SE-SNHG20 group, although cell apoptosis and the expressions of E-cadherin and caspase-3 were significantly higher (P < 0.05). The results revealed that lncRNA SNHG20 could inhibit the chemotherapeutic sensitivity of colon cancer cells to 5-FU by regulating PI3K/AKT pathways. The inhibition of lncRNA SNHG20 expression could promote the apoptosis and proliferation of 5-FU-resistant colon cancer cells. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the metastatic pattern and prognosis of female colon cancer (FCC) to that of male colon cancer (MCC) to ascertain the independent factors impacting the prognosis of patients with FCC. The data of the present study population were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive analysis, the Kaplan-Meier method, and the Cox regression were used to evaluated FCC characteristics and factors associated with prognosis. There were 56,442 patients diagnosed with FCC, of whom 8,817 had distant metastases. Compared to patients with nonmetastatic FCC, a greater proportion of metastatic FCC patients was less than 60 years of age, black race, and grade III-IV. The primary sites were mainly located on the left side and have more possibility to receive chemotherapy and radiotherapy. Compared to metastatic MCC, a higher proportion of metastatic FCC patients ranged over 60 years of age, black race, treated without chemotherapy, and insurance, while the primary site was located on the right side. Liver and lung were the two most common sites of solitary metastases in CC, and among patients with solitary metastases in CC, patients who had lung metastases had a better prognosis than those who developed other types of metastasizes. Patients with FCC with metastases of the liver had a worse prognosis than their MCC counterparts. Cox multivariate regression analysis showed that the risk ratio was higher in metastatic FCC patients compared to those without metastases. We report the survival comparison of metastatic FCC with nonmetastatic FCC through the SEER database. Our results suggest that it has unique clinicopathological features and differs from metastatic MCC. Furthermore, patients with liver metastatic FCC have a worse prognosis than those with MCC. Emphasis on screening for colon cancer in women and additional clinical care should be paid for, especially for patients with FCC with metastatic liver cancer. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) regulate cancer progression and drug resistance. However, the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression is still largely unknown. Hence, this study investigated the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression and found that lncRNA FGD5-AS1 regulated miR-497-5p/PD-L1 axis to promote cancer progression in CC cells in vitro and in vivo. Specifically, we found that lncRNA FGD5-AS1 and PD-L1 tended to be high-expressed, while miR-497-5p was low-expressed in CC tissues and cell lines compared to the normal adjacent tissues and cells. Next, we found that lncRNA FGD5-AS1 positively regulated PD-L1 in CC cells by sponging miR-497-5p. Finally, our gain- and loss-of-function experiments evidenced that the lncRNA FGD5-AS1/miR-497-5p/PD-L1 axis regulates CC progression. Functionally, the data suggested that lncRNA FGD5-AS1 positively regulated while miR-497-5p negatively modulated malignant phenotypes, including cell proliferation, viability, invasion, migration, epithelial-mesenchymal transition (EMT), and tumorigenesis in CC cells. Interestingly, the inhibiting effects of lncRNA FGD5-AS1 ablation on CC development were abrogated by both silencing miR-497-5p and upregulating PD-L1. This study found that lncRNA FGD5-AS1 sponged miR-497-5p to upregulate PD-L1, resulting in CC progression, and provided novel agents for CC diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Aim. This paper investigates the risk factors preventing the reversal and nonreversal of Hartmann's procedure, as a surgical technique that has been performed in our clinic for ten years. Methods. The study involved a ten-year Hartmann's procedure followed up at our center. The patients were divided into Hartmann reversal and nonreversal groups. Groups were examined in terms of age, gender, diagnosis, stage of malignancy, ASA score, comorbidity, perioperative morbidity-mortality, and the length of the operation. Results. Age (p < 0.001), ASA score (p < 0.001), stage in case of malignancy (p = 0.002), and comorbidities (p < 0.001) were significant risk factors. The ratio of patients without any comorbidities to those with one or more comorbidities was 2.63 (95% CI 1.12–6.20). Among the malignant patients, the ratio of early-stage patients to advanced-stage patients in the group with reversal of Hartmann's colostomy was 2.82 (95% CI 1.30–6.10). In addition, the ratio of older patients to younger patients in group 2 was 0.95 (95% CI 0.92–0.98). A univariate analysis revealed that younger patients, those with lower ASA scores, those without comorbidities, and those with early-stage malignancy had a greater chance of closure of the stoma. Conclusion. Although Hartmann's procedure is performed in emergency surgery, the nonreversal of the colostomy is a problem in itself. It should be kept in mind that patients who have high risks are likely to have a permanent stoma. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma (COAD) is among the most common digestive system malignancies worldwide, and its pathogenesis and gene signatures remain unclear. This study explored the genetic characteristics and molecular mechanisms underlying colon cancer development. Three gene expression data sets were obtained from the Gene Expression Omnibus (GEO) database. GEO2R was used to determine differentially expressed genes (DEGs) between COAD and normal tissues. Then, the intersection of the data sets was obtained. Metascape was used to perform the functional enrichment analyses. Next, STRING was used to build protein-protein interaction (PPI) networks. Hub genes were identified and analysed using Cytoscape. Next, survival analysis and expression analysis of the hub genes were performed. ROC curve analysis was performed for further test of the diagnostic efficacy. Finally, alterations in the hub genes were predicted and analysed by cBioPortal. Altogether, 436 DEGs were detected. The DEGs were mainly enriched in cell cycle phase transition, nuclear division, meiotic nuclear division, and cytokinesis. Based on PPI networks, 20 hub genes were selected. Among them, 6 hub genes (CCNB1, CCNA2, AURKA, NCAPG, DLGAP5, and CENPE) showed significant prognostic value in colon cancer (P < 0.05), while 5 hub genes (CDK1, CCNB1, CCNA2, MAD2L1, and DLGAP5) were associated with early colon cancer diagnosis and ROC curve analysis showed good diagnostic accuracy. In conclusion, integrated bioinformatics analysis was used to identify hub genes that reveal the potential mechanism of carcinogenesis and progression of colon cancer. The hub genes might be novel biomarkers for early diagnosis, treatment, and prognosis of colon cancer. [ABSTRACT FROM AUTHOR]

Colon and rectal cancers are the most common kinds of cancer globally. Colon cancer is more prevalent in men than in women. Early detection increases the likelihood of survival, and treatment significantly increases the likelihood of eradicating the disease. The Surveillance, Epidemiology, and End Results (SEER) programme is an excellent source of domestic cancer statistics. SEER includes nearly 30% of the United States population, covering various races and geographic locations. The data are made public via the SEER website when a SEER limited-use data agreement form is submitted and approved. We investigate data from the SEER programme, specifically colon cancer statistics, in this study. Our objective is to create reliable colon cancer survival and conditional survival prediction algorithms. In this study, we have presented an overview of cancer diagnosis methods and the treatments used to cure cancer. This paper presents an analysis of prediction performance of multiple deep learning approaches. The performance of multiple deep learning models is thoroughly examined to discover which algorithm surpasses the others, followed by an investigation of the network's prediction accuracy. The simulation outcomes indicate that automated prediction models can predict colon cancer patient survival. Deep autoencoders displayed the best performance outcomes attaining 97% accuracy and 95% area under curve-receiver operating characteristic (AUC-ROC). [ABSTRACT FROM AUTHOR]

To evaluate the clinical efficacy and safety of the rCCK96-104PE38 targeted drug in patients with colon cancer in general surgery, data of 80 patients with colon cancer who were admitted to the hospital from April 2019 to July 2021 were selected and randomly divided into the treatment group and the control group, with 40 cases in each group. Patients in the treatment group were treated with the rCCK96-104PE38 targeted drug, and those in the control group were treated with oxaliplatin. The treatment efficiency and incidence of adverse reactions were compared between the two groups. The inverse cholecystokinin (CCK96-104) was fused with pseudomonas aeruginosa exotoxin (PE38 toxin) through the gene amplification technique to construct a prokaryotic expression vector. Then, the rCCK96-104PE38 was purified by Ni-nitrilotriacetate (Ni-NTA) affinity chromatography, and the antitumor activity of rCCK96-104PE38 was verified. The results showed that the amplified rCCK96-104PE38 sequence was correct and the pET-28a prokaryotic expression system was adopted to successfully achieve active expression. The purified recombinant protein could induce the apoptosis of colon cancer cells in vitro and inhibit tumor growth in vivo. The total effective rate in the treatment group (80%, 32/40) was higher than that in the control group (60%, 24/40) (P < 0.05). To sum up, the recombinant toxin rCCK96-104PE38 could not only specifically adsorb the colon cancer cells with high expression of CCK2R but also effectively inhibit tumor tissue growth and proliferation. Besides, the rCCK96-104PE38 protein had a good anticancer effect that helped effectively reduce the incidence of adverse reactions in patients, which was worthy of promoting. [ABSTRACT FROM AUTHOR]

Objectives. Lotus leaf is rich in flavonoids, and this study is aimed at examining the inhibitory effect of lotus leaf-enriched flavonoid extract (LLEFE) on HT-29 colon cancer cells through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) expression regulation. Methods. Lotus leaves were extracted by ethanol and purified using FL-3 macroporous resin to create the LLEFE. HT-29 colon cancer cells were tested using various methods: their proliferation was observed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, their survival status was observed by fluorescence staining, their oxidative stress level was observed by biochemical kits, and their mRNA expression was determined by quantitative polymerase chain reaction (qPCR) assay. Additionally, the composition of the flavonoids in lotus leaf was determined by HPLC. Results. The results showed that the proliferation of NCM460 normal human colon cells was not affected by 0–500 μg/mL LLEFE but the proliferation of HT-29 human colon cancer cells decreased. LLEFE increased the LDH level in an HT-29 colon cancer cell culture medium; also increased the superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) level in HT-29 cells; and decreased the malondialdehyde (MDA) level. Further experimental results showed that LLEFE upregulated the expression of SOD1, CAT, and GSH mRNA and downregulated the expression of PI3K, Akt, and mammalian target of rapamycin (mTOR) in HT-29 cells. The high-performance liquid chromatography (HPLC) results showed that kaempferin, hyperoside, astragaloside, phloridzin, and quercetin were the main chemical constituents of lotus leaf. Conclusion. Lotus leaves contain functional flavonoids that inhibit the proliferation of HT-29 colon cancer cells and regulate the expression of PI3K/Akt through five important chemicals. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is involved in various tumor processes, including tumorigenesis, tumor cell migration and metastasis, tumor stemness, and therapeutic resistance. Therefore, it is important to identify the genes most associated with EMT and develop them as therapeutic targets. In this work, we first analyzed EMT hallmark gene expression profiles among 10,535 pan-cancer samples from The Cancer Genome Atlas (TCGA) and divided them into EMT high and EMT low groups according to the metagene scores. Then, we identified 12 genes that were most associated with high EMT metagene score (R > 0.9) in 329 colon adenocarcinoma (COAD) patients. Among them, only 4 genes (AEBP1, KCNE4, GFPT2, and FAM26E) had statistically significant differences in prognosis (P < 0.05). Next, we selected AEBP1 as a candidate and showed that AEBP1 mRNA levels and EMT biomarkers strongly coexpressed in 329 COAD samples. In addition, AEBP1 was highly expressed and associated with poor clinical outcomes and prognosis in COAD patients. Finally, to explore whether AEBP1-mediated EMT was related to the tumor microenvironment (TME), we examined AEBP1 expression levels at the single-cell levels. Our results showed that AEBP1 levels were extremely high in tumor-associated fibroblasts, which may induce EMT. AEBP1 expression was also positively correlated with the expression of fibroblast biomarkers and also with EMT metascores, suggesting that AEBP1-mediated EMT may be associated with the stimulation of fibroblast activation. Therefore, AEBP1 may be a promising target for EMT inhibition, which reduces cancer metastasis and drug resistance in COAD patients. [ABSTRACT FROM AUTHOR]

Aim. The aim of our work was to determine the utility of DNM1 as a biomarker for the diagnosis and prognosis of colon cancer (CC). Methods. DNM1 expression variations in CC vs. normal tissues were investigated using The Cancer Genome Atlas (TCGA) database. The association of DNM1 expression levels with the clinicopathological variables in CC prognosis was investigated using logistic regression analyses. Independent prognostic factors for CC were evaluated using univariate and multivariate Cox regression analyses. The correlation between DNM1 expression and immune cell infiltration was estimated using single-sample Gene Set Enrichment Analysis (ssGSEA). Results. DNM1 expression in CC tissues was significantly higher than that in normal tissues. High DNM1 expression was significantly correlated with M stage, N stage, perineural invasion and lymphatic invasion and predicted poor prognosis. The univariate analysis highlighted that DNM1 was an independent CC risk factor. Results of ssGSEA showed that DNM1 was linked to several cancer-related pathways, including the neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, ECM-receptor interaction, dilated cardiomyopathy, and calcium signaling pathway. Moreover, DNM1 expression was positively correlated with the level of infiltration by Neutrophils, Tregs, NK cells, and Macrophages. Conclusion. DNM1 has a significant function and has diagnostic and prognostic potential for CC. [ABSTRACT FROM AUTHOR]

Background. Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). Methods. The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. Results. The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. Conclusion. We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy. [ABSTRACT FROM AUTHOR]

A new master-slave binary grey wolf optimizer (MSBGWO) is introduced. A master-slave learning scheme is introduced to the grey wolf optimizer (GWO) to improve its ability to explore and get better solutions in a search space. Five high-dimensional biomedical datasets are used to test the ability of MSBGWO in feature selection. The experimental results of MSBGWO are superior in terms of classification accuracy, precision, recall, F -measure, and number of features selected when compared to those of the binary grey wolf optimizer version 2 (BGWO2), binary genetic algorithm (BGA), binary particle swarm optimization (BPSO), differential evolution (DE) algorithm, and sine-cosine algorithm (SCA). [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer (CRC) is recognized as one of the most common malignancies with a high mortality rate worldwide, supporting the necessity for an effective novel antitumor drug to improve current therapy's effectiveness. Substance P (SP) is the essential member of the tachykinins (TKs) family, which binds to the specific receptors, known as neurokinin-1 receptor (NK1R), exerting its multiple influences such as tumor cell proliferation, angiogenesis, and metastasis. Aprepitant, as a specific NK1R antagonist, is suggested as a novel antitumor agent, promoting apoptotic processes in tumor cells; however, the exact antitumor mechanism of aprepitant on molecular signaling in CRC is not entirely known. Method. The resazurin assay was conducted to assess the cytotoxic effects of aprepitant on the viability of the CRC cell line (SW480). The level of reactive oxygen species (ROS) was measured after 24-hour treatment with SP and aprepitant. PI/annexin V-FITC staining was conducted to assess apoptosis. Also, the expression of NF-κB antiapoptotic target genes and proapoptotic p53 target genes was measured by real-time- (RT-) PCR assay. Western blotting assay was performed to determine the expression of PI3k/AKT/NF-κB proteins. Results. We found that aprepitant stimulates apoptotic cell death and attenuates the PI3K/Akt pathway and its downstream proapoptotic target gene, including NF-κB in SW480 cells. Also, the obtained results from the quantitative RT-PCR assay showed that aprepitant could decrease the level of mRNA of NF-κB antiapoptotic target genes. Conclusion. Towards this end, this study suggests that SP/NK1R system plays a vital role in the development of CRC, and pharmaceutical targeting of NK1R using aprepitant might be a promising treatment against CRC. [ABSTRACT FROM AUTHOR]

Objective. To analyze the molecular regulation network of circular RNA (circRNA) in colon cancer (CC) by bioinformatics method. Methods. hsa_circ_0007843 and hsa_circ_0007331 proved to be associated with CC in previous studies were chosen as the research object. ConSite database was used to predict the transcription factors associated with circRNA, and the CC-associated transcription factors were screened out after intersection. The CircInteractome database was used to predict the RNA-binding proteins (RBPs) interacting with circRNAs and screen out the CC-associated RBPs after an intersection. Furthermore, the CircInteractome database was used to predict the miRNAs interrelated with circRNAs, and the HMDD v3.2 database was used to search for miRNAs associated with CC. The target mRNAs of miRNA were predicted by the miRWalk v3.0 database. CC-associated target genes were screened out from the GeneCards database, and the upregulated genes were enriched and analyzed by the FunRich 3.1.3 software. Finally, the molecular regulatory network diagram of circRNA in CC was plotted. Results. The ConSite database predicted a total of 14 common transcription factors of hsa_circ_0007843 and hsa_circ_0007331, among which Snail, SOX17, HNF3, C-FOS, and RORα-1 were related to CC. The CircInteractome database predicted that the RBPs interacting with these two circRNAs were AGO2 and EIF4A3, and both of them were related to CC. A total of 17 miRNAs interacting with hsa_circ_0007843 and hsa_circ_0007331 were predicted by CircInteractome database. miR-145-5p, miR-21, miR-330-5p, miR-326, and miR-766 were associated with CC according to the HMDDv3.2 database. miR-145-5p and miR-330-5p, lowly expressed in CC, were analyzed in the follow-up study. A total of 676 common target genes of these two miRNAs were predicted by the miRWalk3.0 database. And 57 target genes were involved in the occurrence and development of CC from the GeneCards database, with 23 genes downregulated and 34 genes upregulated. Additionally, GO analysis showed that the 34 upregulated genes were mainly enriched in biological processes such as signal transduction and cell communication. KEGG pathway analysis showed that the upregulated genes were closely related to integrin, ErbB receptor, and ALK1 signal pathways. Finally, a complete regulatory network of hsa_circ_0007843 and hsa_circ_0007331 in CC was proposed, whereby each one of the participants was either directly or indirectly associated and whose deregulation may result in CC progression. Conclusion. Predicting the molecular regulatory network of circRNAs by bioinformatics provides a new theoretical basis for further occurrence and development pathogenesis of CC and good guidance for future experimental research. [ABSTRACT FROM AUTHOR]

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a family of enzymes. However, the clinical and functional roles of PLOD3 in colon adenocarcinoma (COAD) have not been investigated. The present study found that PLOD3 was highly upregulated in COAD, which may be resulted from its aberrant DNA methylation. The upregulation of both PLOD3 mRNA and protein was confirmed in our tissue samples. Moreover, high PLOD3 was identified to be associated with unfavorable prognosis in COAD. As genome instability is a hallmark of cancer, PLOD3 was expressed higher in COAD samples with high chromosomal instability (CIN-high) than those with low CIN (CIN-low) and higher in those with low MSI than high MSI, indicating that PLOD3 expression was associated with tumor genomic instability. Furthermore, immune cells showed significantly different infiltrating levels between the high and low PLOD3 expression groups, and the immune score was negatively correlated with PLOD3 expression and higher in samples with low PLOD3 expression, suggesting that high PLOD3 expression was associated with reduced immune cell infiltrating levels in COAD. To further uncover the underlying mechanism of PLOD3 in PLOD3, we compared the COAD samples of high PLOD3 expression with those of low PLOD3 expression and found that high expression of PLOD3 was associated with reduced expression of immune regulators and enhanced activities of two tumor-promoting pathways, including gluconeogenesis and TGF-beta signaling in epithelial-mesenchymal transition (EMT), suggesting that high expression of PLOD3 causes poor prognosis in COAD by weakening the immune cell infiltration and enhancing activities of tumor-promoting pathways. In summary, the present study highlights the importance of PLOD3 and provides the evidence about the functional role of PLOD3 in COAD. [ABSTRACT FROM AUTHOR]

Imaging of CD8 receptors on T-cells by positron emission tomography (PET) has been considered a promising strategy for monitoring the treatment response to immunotherapy. In this study, a trial of imaging CD8 with our newly developed sequential multiple-agent receptor targeting (SMART) technology was conducted. Mice bearing a subcutaneous colorectal CT26 tumor received three times different immunotherapy treatments (PD1 or CTLA4 or combined). On either day 7 or day 14 after the first time treatment, the PET imaging study was performed with sequentially administered TCO-modified anti-CD8 antibody and 64Cu-labeled MeTz-NOTA-RGD. However, no positive response was detected, probably due to (1) inappropriate selection of biomarkers for the SMART strategy, (2) limited TCO modification on the anti-CD8 antibody, and (3) inadequate response of the CT26 tumor to the selected immunotherapies. Therefore, the potential of applying SMART in imaging CD8 was not demonstrated in this study, and further optimization will be necessary before it can be applied in imaging CD8. [ABSTRACT FROM AUTHOR]

Purpose. Chemoresistance is a challenge of improving chemotherapeutic efficacy and prolonging survival time for patients with colorectal cancer (CRC); it is the major cause of frequent recurrence, rapid metastasis, and poor prognosis for CRC patients. FXYD6 is a regulator of Na+/K+-ATPase which is depressed in chemoresistant CRC patients. However, the biological roles of FXYD6 on regulating chemoresistance in CRC are still unclear. Methods. GSE3964 and GSE69657 from GEO DataSets were used to analyze the relationship of genes and chemoresistance. The FXYD6 expression level was detected by western blotting and real-time PCR and also analyzed from TCGA DataSet. To investigate the functional role of FXYD6 and ATP-α1, FXYD6 and ATP-α1 functional cell models were constructed. Drug sensitivity and cell proliferation were performed by MTT assay. Autophagy and apoptosis were conducted by autophagy fluorescence analysis and flow cytometric analysis, respectively. Autophagy and apoptosis markers were tested by western blotting. Results. FXYD6 was downregulated in CRC resistant patients and irinotecan- (Iri-) resistant SW620 cells (SW620/Iri). FXYD6 silence inhibited cell apoptosis and enhanced prosurvival autophagy, whereas FXYD6 overexpression produced the opposite effect which alleviated the drug resistance to irinotecan and oxaliplatin of CRC cells. FXYD6 regulates chemosensitivity by mediating the expression of Na+/K+-ATPase α1 and affecting cell autophagy and apoptosis in colorectal cancer. Conclusion. FXYD6 functions as a chemosensitivity regulator which may predict the curative effect of chemotherapy in colorectal cancer. [ABSTRACT FROM AUTHOR]

Background. Body mass index, measured at colorectal cancer (CRC) diagnosis has been associated with recurrence and survival outcomes. Computed tomography- (CT-) defined body compositions accurately reflect body mass, but there was no consistent perspective on the influence of visceral adipose tissue (VAT) and skeletal muscle mass (SM) on the prognosis of nonmetastasis CRC, especially in the patients underwent surgery and regularly standard chemotherapy. Methods. We investigated the associations of CT-quantified body composition (VAT and SM) with CRC patients successively underwent surgery and regular 8-12 of periods standard chemotherapy. All of the CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body compositions was analyzed using the Cox regression model, and precise clinical nomograms were established. Results. In XELOX-treated patients, progression-free survival (PFS) (P = 0.025) and overall survival (OS) (P = 0.032) were lower in the high-SM than in the low-SM group. The univariate analysis demonstrated that compared with low-SM patients, patients with high-SM showed a strikingly poor prognosis in both OS (P = 0.0512) and PFS in the T4 subgroup (P = 0.0417), while contrary to the T2-3 subgroup. Conclusions. CT-quantified body compositions have a significant influence on CRC patients successively underwent curative resection and regularly standard chemotherapy with the endpoints of 1-year, 3-year, and 5-year both OS and PFS. Patients with high-SM showed a strikingly poor prognosis in OS and PFS in the T4 subgroup; however, the prognosis role of body composition was opposite in T2-3 patients. [ABSTRACT FROM AUTHOR]

Background. Colon cancer (CC) is a malignant tumor with a high incidence and poor prognosis. Accumulating evidence shows that the immune signature plays an important role in the tumorigenesis, progression, and prognosis of CC. Our study is aimed at establishing a novel robust immune-related gene pair signature for predicting the prognosis of CC. Methods. Gene expression profiles and corresponding clinical information are obtained from two public data sets: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, GSE39582). We screened out immune-related gene pairs (IRGPs) associated with prognosis in the discovery cohort. Lasso-Cox proportional hazard regression was used to develop the best prognostic signature model. According to this, the patients in the validation cohort were divided into high immune-risk group and low immune-risk group, and the prediction ability of the signature model was verified by survival analysis and independent prognostic analysis. Results. A total of 17 IRGPs composed of 26 IRGs were used to construct a prognostic-related risk scoring model. This model accurately predicted the prognosis of CC patients, and the patients in the high immune-risk group indicated poor prognosis in the discovery cohort and validation cohort. Besides, whether in univariate or multivariate analysis, the IRGP signature was an independent prognostic factor. T cell CD4 memory resting in the low-risk group was significantly higher than that in the high-risk group. Functional analysis showed that the biological processes of the low-risk group included "TCA cycle" and "RNA degradation," while the high-risk group was enriched in the "CAMs" and "focal adhesion" pathways. Conclusion. We have successfully established a signature model composed of 17 IRGPs, which provides a novel idea to predict the prognosis of CC patients. [ABSTRACT FROM AUTHOR]

This study was for verifying that transfecting colon cancer cells (CCCs) with lncRNA NEAT1 packed with siRNA chitosan nanoparticles (CNPs) can suppress lncRNA NEAT1 and biological behaviors of the cells. siRNA targeting lncRNA NEAT1 expression vector was constructed and then transfected into CCCs after being packed with CNPs. Subsequently, the impact of the transfection on biological behaviors of the cells was evaluated. As a result, with high expression in CCCs, NEAT1 was negatively bound up with miR-377-3p in cases with colon cancer (CC), and dual luciferase reporter assay confirmed the potential binding region. Additionally, after downregulating NEAT1 in CCCs, transfection of NEAT1 siRNA packed with CNPs brought a great inhibition on cell proliferation and a promotion on apoptosis, and inhibiting miR-377-3p was able to offset the role of silencing NEAT1 in CCCs. Therefore, in our opinion, NEAT1 siRNA packed with CNPs can hinder the growth and metastasis of CCCs by knocking down NEAT1 in CC, and its mechanism may be achieved by targeting miR-377-3p, which offers a novel direction for treating CC. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of the current meta-analysis was to evaluate whether multidisciplinary team improved overall survival of colorectal cancer. Methods. PubMed, EMBASE, and Cochrane Library database were searched from inception to October 25, 2020. The hazard ratio (HR) and 95% confidence (CI) of overall survival (OS) were calculated. Results. A total of 11 studies with 30814 patients were included in this meta-analysis. After pooling the HRs, the MDT group was associated with better OS compared with the non-MDT group (HR = 0.81 , 95% CI 0.69-0.94, p = 0.005). In subgroup analysis of stage IV colorectal cancer, the MDT group was associated with better OS as well (HR = 0.73 , 95% CI 0.59-0.90, p = 0.004). However, in terms of postoperative mortality, no significant difference was found between MDT and non-MDT groups (OR = 0.84 , 95% CI 0.44-1.61, p = 0.60). Conclusion. MDT could improve OS of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Although colorectal cancer (CRC) is common, there is a paucity of information regarding its molecular pathogenesis. Studies have shown that miRNAs play pivotal roles in the development and progression of CRC. There is a need to further investigate the biological functions of miRNAs in CRC. In particular, it has been reported that miR-942-5p exhibits tumor-suppressive properties. Thus, we analyzed the functional significance of miR-942-5p in CRC and the underlying molecular mechanisms. We found that miR-942-5p was downregulated in CRC tissues and cells. Cell Counting Kit-8, EdU, and colony formation assays revealed that the overexpression of miR-942-5p by mimics inhibited the proliferation of CRC cells. Use of the miR-942-5p inhibitor effectively enhanced the proliferative potential of CRC cells. Further, in vivo xenograft experiments confirmed these results. Increased expression of miR-942-5p suppressed the invasion, migration, and epithelial-mesenchymal transition of CRC cell lines, while decreased miR-942-5p expression had the opposite effect. CCBE1, a secretory molecule for lymphangiogenesis, was established as a downstream target of miR-942-5p, and its expression was inversely correlated with the expression of miR-942-5p in CRC cells. Additionally, cotransfection of the miR-942-5p inhibitor with si-CCBE1 into CRC cells reversed the effects induced by miR-942-5p overexpression. In conclusion, we confirmed that miR-942-5p exerts oncogenic actions in CRC by targeting CCBE1 and identified miR-942-5p as a potential clinical biomarker for CRC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Moderate folic acid (FA) intake is an effective strategy that slows colorectal cancer (CRC) progression. However, high consumption of FA may trigger the transition of precancerous tissue towards malignancy. MicroRNAs (miRNAs) are considered to be potential biomarkers of CRC. Thus, identification of miRNAs of dysregulated genes in CRC cells by detailed analysis of mRNA and miRNA expression profile in the context of FA deficiency could substantially increase our understanding of its oncogenesis. mRNA-seq and miRNA-seq analyses were utilized to investigate the expression of miRNAs in FA-deficient CRC cell line–HCT116 through massive parallel sequencing technology. A total of 38 mRNAs and 168 miRNAs were identified to be differentially expressed between CRC groups with or without FA deficiency. We constructed an miRNA-mRNA network for the vital regulatory miRNAs altered in FA-deficient CRC cells. The mRNAs and miRNAs validated by Western blotting and RT-qPCR were consistent with the sequencing results. Results showed that FA deficiency upregulated some miRNAs thereby inhibiting the expression of critical genes in the endoplasmic reticulum (ER) stress pathway. Dysregulated miRNAs in our miRNA-mRNA network could contribute to CRC cell in response to deficient FA. This work reveals novel molecular targets that are likely to provide therapeutic interventions for CRC. [ABSTRACT FROM AUTHOR]

Background. Hsp70 (heat shock protein 70) plays a key role in carcinogenesis and cancer progression. However, the relationship between the Hsp70 expression level and the colorectal cancer patient survival is unknown. This study is aimed at investigating the relationship between Hsp70 and the prognosis of colorectal carcinoma patients. Methods. PubMed, Web of Science, and Embase were used for systematic computer literature retrieval. Stata SE14.0 software was used for quantitative meta-analysis. Besides, data was extracted from selected articles. Relationships between Hsp70 expression level and prognosis were further studied. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were also computed. Results. A total of 11 potentially eligible studies with 2269 patients were identified in 10 tumors from PubMed, Web of Science, and Embase. Hsp70 overexpression was associated with poor overall survival (OS) and disease-free survival (DFS) in colorectal carcinoma patients (HRs, 0.65 (95% CI: 0.52-0.78) and 0.77 (95% CI: 0.23-1.32), respectively). Conclusions. Hsp70 overexpression can predict poor survival in colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Background. Colon cancer has high morbidity and mortality rates among cancers. Existing clinical staging systems cannot accurately assess the prognostic risk of colon cancer patients. This study was aimed at improving the prognostic performance of the colon cancer clinical staging system through knowledge-based clinical-molecular integrated analysis. Methods. 374 samples from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset were used as the discovery set. 98 samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) dataset were used as the validation set. After converting gene expression data into pathway dysregulation scores (PDSs), the random survival forest and Cox model were used to identify the best prognostic supplementary factors. The corresponding clinical-molecular integrated prognostic model was built, and the improvement of prognostic performance was assessed by comparing with the clinical prognostic model. Results. The PDS of 14 pathways played important roles in prognostic prediction together with clinical prognostic factors through the random survival forest. Further screening with the Cox model revealed that the PDS of the pathway hsa00532 was the best clinical prognostic supplementary factor. The integrated prognostic model constructed with clinical factors and the identified molecular factor was superior to the clinical prognostic model in discriminative performance. Kaplan-Meier (KM) curves of patients grouped by PDS suggested that patients with a higher PDS had a poorer prognosis, and stage II patients could be distinctly distinguished. Conclusions. Based on the knowledge-based clinical-molecular integrated analysis, a clinical-molecular integrated prognostic model and corresponding nomogram for colon cancer overall survival prognosis was built, which showed better prognostic performance than the clinical prognostic model. The PDS of the pathway hsa00532 is a considerable clinical prognostic supplementary factor for colon cancer and may represent a potential prognostic marker for stage II colon cancer. The PDS calculation involves only 16 genes, which supports its potential for clinical application. [ABSTRACT FROM AUTHOR]

Objectives. Chemotherapy is considered to be essential in the treatment of patients with colorectal cancer (CRC), but drug resistance reduces its efficacy. Many patients with advanced CRC eventually show resistance to 5-fluorouracil (5-FU) therapy. Synergistic and potentiating effects of combination therapy, using herbal and chemical drugs, can improve patients' response. Zerumbone (ZER), which is derived from ginger, has been studied for its growth inhibitory function in various types of cancer. Methods. The cytotoxic effects of ZER and 5-FU alone and their combination, on the SW48 and HCT-116 cells, were examined, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mRNA and protein levels of β-catenin, survivin, and vimentin were measured in treated CRC cells, using qRT-PCR and western blot. Colony formation assay, scratch test, and flow cytometry were performed to detect the changes of proliferation, migration, and apoptosis. Key Findings. In HCT-116- and SW48-treated cells, the proliferation, the gene and protein expression levels of the markers, the migration, the colony formation, and the survival rates were all significantly reduced compared to the control groups, and the sharpest decline was observed in the 5-FU+ZER treatment groups. Conclusions. Combination therapy has shown promising results in CRC cells, especially in drug-resistant cells. [ABSTRACT FROM AUTHOR]

Background. Clausena excavata Burum. f. has long been applied in ethnomedicine for the treatment of various disorders like rhinitis, headache, cough, wound healing, fever, and detoxification. This study is aimed at investigating the antibacterial activity against Enterococcus faecalis ATCC 49532 using AlamarBlue assay and atomic force microscopy (AFM) as well as the cytotoxicity, anticancer, and phytotoxicity of C. excavata. Method. Bacterial cell viability was performed by using microplate AlamarBlue assay. Atomic force microscopy was used to determine morphological changes in the surface of bacterial cells. Cytotoxicity and phytotoxicity were determined by brine shrimp lethality and Lemna minor bioassay. Caco-2 (colorectal adenocarcinoma) cell line was used for the evaluation of the anticancer effects. Result. Among the fractions tested, ethyl acetate (EA) fraction was found to be active with minimum inhibitory concentration (MIC) of 750 μg/mL against E. faecalis, but other fractions were found to be insensitive to bacterial growth. Microscopically, the EA fraction-treated bacteria showed highly damaged cells with their cytoplasmic content scattered all over. The L C 50 value of the EA fraction against brine shrimp was more than 1000 μg/mL showing the nontoxic nature of this fraction. Chloroform (CH), EA, and methanol (MOH) fractions of C. excavata were highly herbicidal at the concentration of 1000 μg/mL. EA inhibited Caco-2 cell line with an I C 50 of 20 μg/mL. Conclusions. This study is the first to reveal anti-E. faecalis property of EA fraction of C. excavata leaves, natural herbicidal, and anticancer agents thus highlight the potential compound present in its leaf which needs to be isolated and tested against multidrug-resistant E. faecalis. [ABSTRACT FROM AUTHOR]

Background. A prediction model can be developed to predict the risk of cancer-related cognitive impairment in colorectal cancer patients after chemotherapy. Methods. A regression analysis was performed on 386 colorectal cancer patients who had undergone chemotherapy. Three prediction models (random forest, logistic regression, and support vector machine models) were constructed using collected clinical and pathological data of the patients. Calibration and ROC curves and C -indexes were used to evaluate the selected models. A decision curve analysis (DCA) was used to determine the clinical utility of the line graph. Results. Three prediction models including a random forest, a logistic regression, and a support vector machine were constructed. The logistic regression model had the strongest predictive power with an area under the curve (AUC) of 0.799. Age, BMI, colostomy, complications, CRA, depression, diabetes, QLQ-C30 score, exercise, hypercholesterolemia, diet, marital status, education level, and pathological stage were included in the nomogram. The C -index (0.826) and calibration curve showed that the nomogram had good predictive ability and the DCA curves indicated that the model had strong clinical utility. Conclusions. A prediction model with good predictive ability and practical clinical value can be developed for predicting the risk of cognitive impairment in colorectal cancer after chemotherapy. [ABSTRACT FROM AUTHOR]

Active immunotherapy against cancer is based on immune system stimulation, triggering efficient and long-lasting antigen-specific immune responses. Immunization strategies using whole dead cells from tumor tissue, containing specific antigens inside, have become a promising approach, providing efficient lymphocyte activation through dendritic cells (DCs). In this work, we generate whole dead tumor cells from CT26, E.G7, and EL4 live tumor cells as antigen sources, which termed immunogenic cell bodies (ICBs), generated by a simple and cost-efficient starvation-protocol, in order to determine whether are capable of inducing a transversal anticancer response regardless of the tumor type, in a similar way to what we describe previously with B16 melanoma. We evaluated the anticancer effects of immunization with doses of ICBs in syngeneic murine tumor models. Our results showed that mice's immunization with ICBs-E.G7 and ICBs-CT26 generate 18% and 25% of tumor-free animals, respectively. On the other hand, all carrying tumor-animals and immunized with ICBs, including ICBs-EL4, showed a significant delay in their growth compared to not immunized animals. These effects relate to DCs maturation, cytokine production, increase in CD4+T-bet+ and CD4+ROR-γt+ population, and decrease of T regulatory lymphocytes in the spleen. Altogether, our data suggest that whole dead tumor cell-based cancer immunotherapy generated by a simple starvation protocol is a promising way to develop complementary, innovative, and affordable antitumor therapies in a broad spectrum of tumors. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to explore the role of preoperative fibrinogen-to-prealbumin ratio (FPR) in evaluating the prognosis of patients with stage I–III colorectal cancer (CRC). Methods. This retrospective study enrolled 584 stage I–III CRC patients undergoing surgical resection. Logistic regression analysis was used to explore the correlation between FPR and postoperative complications. The Kaplan-Meier curve and Cox proportional hazards model were used to identify the prognostic factors. The nomograms were constructed based on the prognostic factors. The concordance index and calibration curve were used to determine the accuracy of the nomograms. Time-dependent receiver operating characteristic was used to compare the predictive prognostic efficacy of nomograms and TNM stage. Results. FPR was determined to be an independent factor affecting postoperative complications. Patients with a low-FPR had a significantly better prognosis than those with a high-FPR (disease-free survival, p = 0.028 ; overall survival, p = 0.027), especially patients with stage I CRC (disease-free survival, p = 0.015 ; overall survival, p = 0.017). The Cox proportional hazards model identified FPR as an independent poor prognostic factor of disease-free survival (hazard ratio HR = 1.459 , 95% confidence interval CI = 1.074 –1.954, p = 0.011) and overall survival (HR = 1.405 , 95% CI = 1.034 –1.909, p = 0.030). The prognostic nomograms had good accuracy and were superior to the traditional TNM stage. Conclusions. FPR is a potential indicator for predicting short- and long-term prognosis of stage I–III CRC patients undergoing surgical resection. [ABSTRACT FROM AUTHOR]

Purpose. The epithelial–mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets. Methods. A series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients. Results. GLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients. Conclusions. In summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression. [ABSTRACT FROM AUTHOR]

Background. A female prognostic advantage in younger individuals has been demonstrated in various cancers. Several large-scale analyses based on different racial backgrounds have reported inconsistent results in colorectal cancer. The aim of the present study was to evaluate the prognostic value of sex and age in patients with colorectal cancer of different ethnic groups. Methods. We identified 71,812 eligible patients from the Surveillance, Epidemiology and End Results database. According to age at diagnosis, the patients were categorized into premenopausal age (≤45 yrs), menopausal age (46–54 yrs), and postmenopausal age (≥55 yrs) subgroups for further analysis. Results. Multivariate analysis identified the female survival advantage to be significant in the premenopausal age subgroup (P = 0.002 , HR (95% CI): 0.73 (0.60–0.89)), diminished in the menopausal age subgroup (P = 0.09), and absent in the postmenopausal age subgroup (P = 0.96). Furthermore, the female survival advantage at premenopausal age was significant only in white patients (P = 0.001 , HR (95% CI): 0.68 (0.54–0.87)) and not in either American Indian/Alaska Native or Asian or Pacific Islander patients. There was a trend of better survival of females in black patients (P = 0.07). Conclusions. Sex was a major prognostic factor in colorectal cancer patients, especially premenopausal women, and the difference was also associated with race. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) plays an important role in many cancers. However, few studies have examined the role of m6A in colorectal CRC. To examine the effect of m6A on CRC, we studied the genome of 591 CRC cases from The Cancer Genome Atlas (TCGA). The relationship between the messenger RNA (mRNA) expression, copy number variation (CNVs), and mutations of m6A "Writers," "Readers," and "Erasers," prognosis, immune cell infiltration, and genetic mutations in CRC cases were analyzed. CNVs and mutations were found in thirteen m6A regulators. As expected, gain and amplification of m6A regulators increased the mRNA expression of these regulators, while deletion led to reduction in the mRNA expression. Moreover, CNVs and mutation of these regulators were significantly associated with APC, TP53, and microsatellite instability (MSI) status (p < 0.001 , p < 0.001 , and p = 0.029 , respectively). CNVs of m6A regulators also correlated with inferred immune cell infiltration in CRC tissues, especially in colon tissues. Additionally, alterations of RBM15, YTHDF2, YTHDC1, YTHDC2, and METTL14 genes were related to the worse overall survival and disease-free survival (DFS) of CRC patients. Specifically, the deletion status of "Writers" was also correlated to the DFS of CRC patients (p = 0.02). Gene set enrichment analysis found that FTO was involved in mRNA 3 ′ end processing, polyubiquitin binding, and RNA polymerase promoter elongation, while YTHDC1 was related to interferon-alpha and gamma response. In conclusion, a novel relationship was identified between CNVs and mutations of m6A regulators with prognosis and inferred immune function of CRC. These findings will improve the understanding of the relationship of m6A in CRC. [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer (CRC) is the second most common cause of cancer death in the United States and the third most common cancer globally. The incidence of CRC tends to be younger, and we urgently need a reliable prognostic assessment strategy. Methods. Protein expression profile and clinical information of 390 CRC patients/samples were downloaded from the TCPA and TCGA database, respectively. The Kaplan-Meier, Cox regression, and Pearson correlation analysis were applied in this study. Results. Based on the TCPA and TCGA database, we screened 6 hub proteins and first constructed protein risk signature, all of which were significantly associated with CRC patients' overall survival (OS). The risk score was an independent prognostic factor and significantly related with the size of the tumor in situ (T). 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database. Next, 40 coexpressed proteins of 6 hub proteins were extracted from the TCPA database. In the protein-protein interaction (PPI) network, HER1, HER2, and CTNNB1 were at the center. Function enrichment analysis illustrated that 46 proteins were mainly involved in the EGFR (HER1) tyrosine kinase inhibitor resistance pathway. Conclusion. Studies indicated that 6 hub proteins might be considered as new targets for CRC therapies, and the protein risk signature can be used to predict the OS of CRC patients. [ABSTRACT FROM AUTHOR]

Introduction. Although cetuximab has been widely used in the treatment of colon cancer, a large number of patients eventually develop drug resistance. Therefore, it is essential to clarify the mechanism of drug resistance. Methods. In this study, we combined in silico analysis and a single guide RNA (sgRNA) library to locate cetuximab-sensitive genes. Cell proliferation, apoptosis, and cell cycle were assessed to validate the change in cetuximab sensitivity. Finally, western blotting was performed to detect changes in epidermal growth factor (EGFR) upstream and downstream genes. Results. Using in silico analysis and the sgRNA library, MEIS3 was confirmed as the cetuximab-sensitive gene. Further experiments indicated that the expression of MEIS3 could determine the level of cetuximab. Meanwhile, MEIS3-inhibited cells were sensitive to mesenchymal epithelial transition factor (c-Met) and protein kinase B (Akt) inhibitors, which is related to the change in phosphorylation of c-Met and degradation of Akt. Conclusion. MEIS3 modified the sensitivity to cetuximab through c-Met and Akt. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggested that lncRNA MALAT1 plays critical roles in the commencement and progression of malignant cancers. Nevertheless, the function of MALAT1 in colorectal cancer (CRC) remains largely unknown. In the present study, we reported that MALAT1 expression is significantly upregulated in CRC and correlated with advanced TNM stage, lymph node metastasis, and worse prognosis in patients. Functional assays revealed that MALAT1 knockdown reduced CRC cell growth and invasion abilities in vitro. Mechanistically, we discovered that MALAT1 may serve as a competing endogenous RNA (ceRNA) to miR-508-5p in CRC progression. Bioinformatics analysis and luciferase assays confirmed that RAB14 acts as a target of miR-508-5p. In addition, downregulation of RAB14 reduced the progression of CRC. Collectively, our findings indicated that MALAT1 could promote CRC progress by sponging miR-508-5p and enhancing RAB14 expression, which provides a therapeutic target in CRC treatment. [ABSTRACT FROM AUTHOR]

Background. S100 family genes exclusively encode at least 20 calcium-binding proteins, which possess a wide spectrum of intracellular and extracellular functions in vertebrates. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). However, the diverse expression patterns and prognostic roles of distinct S100 genes in CRC have not been fully elucidated. Methods. In the current study, we analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Expressions and mutations of S100 family genes were analyzed using the cBioPortal, and protein-protein interaction (PPI) networks of S100 proteins and their mutation-related coexpressed genes were analyzed using STRING and Cytoscape. Results. We observed that the mRNA expression levels of S100A2, S100A3, S100A9, S100A11, and S100P were higher and the level of S100B was lower in CRC tissues than those in normal colon mucosa. A high S100A10 levels was associated with advanced-stage CRC. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers. Unexpectedly, most of S100 family genes showed no significant prognostic values in CRC. Conclusions. Our findings, though still need to be ascertained, offer novel insights into the prognostic implications of the S100 family in CRC and will inspire more clinical trials to explore potential S100-targeted inhibitors for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Aims. The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients. Methods. The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database. These patients were divided into training and validation datasets. A risk score model was established based on Kaplan-Meier and multivariate Cox regression analysis of training cohort and tested in validation cohort. Results. Among total 14,626 DNA methylation candidate markers, we found that a three-DNA methylation signature (NR1H2, SCRIB, and UACA) was significantly associated with overall survival of CRC patients. Subgroup analysis indicated that this signature could predict overall survival of CRC patients regardless of age and gender. Conclusions. We established a prognostic model consisted of 3-DNA methylation sites, which could be used as potential biomarker to evaluate the prognosis of CRC patients. [ABSTRACT FROM AUTHOR]

Different opinions exist on the relationship between the C-reactive protein-to-albumin ratio (CAR) and the prognosis of colon cancer. This study is aimed at evaluating the relationship between CAR and prognosis of stage II–III colon cancer and establishing a clinical prognosis model. Patients were randomised to a training set (566 cases) and validation set (110 cases). The relationship between CAR and clinicopathological variables was calculated, and the Kaplan-Meier method was used to analyse the overall survival (OS) rate of colon cancer. In the training set, colon cancer independent risk factors were included in the prognosis model and then tested in the validation set. The accuracy and discrimination of the model were assessed using the C-index and calibration curves. Compared with patients with low CAR, patients with high CAR showed significantly poorer survival (P = 0.020). In the multivariate analysis, CAR, carcinoembryonic antigen (CEA), lymph node metastasis, operation mode, and perineural invasion were identified as independent prognostic indicators and adopted to establish the prediction model. The C-index of the nomogram for predicting OS reached 0.751 in the training set and 0.719 in the validation set. The calibration curve exhibited good consistency. In the present study, the CAR may be an independent prognostic factor for stage II–III colon cancer, and the nomogram has a certain predictive value. However, further prospective large-sample research needs to be conducted to validate our findings. [ABSTRACT FROM AUTHOR]

Increasing study has validated that long noncoding RNAs (lncRNAs) are involved in the growth and metastasis of colon cancer. LINC01207 has been reported to play vital roles in certain types of cancer, while the precise function of LINC01207 in the progression of colon cancer remains unclear. The objective of this study was to investigate the effect of LINC01207 on the growth and metastasis of colon cancer cells and to explore the underlying mechanism. We found that the expression of LINC01207 was significantly upregulated in colon adenocarcinoma tissues compared with normal tissues by the GEPIA database. Notably, silencing of LINC01207 significantly suppressed the proliferation, migration, and invasion abilities of SW480 and HT-29 cells. Mechanistically, our data demonstrated that LINC01207 could sponge miR-3125 in colon cancer cells. Moreover, miR-3125 could directly target TRIM22 and negatively regulate its expression. Rescue assays revealed that miR-3125 inhibitor or TRIM22 overexpression significantly reversed the repressive role of LINC01207 knockdown in colon cancer cell proliferation and invasion. In conclusion, LINC01207 exerts an oncogenic role in the progression of colon cancer by absorbing miR-3125 to modulating TRIM22 expression. [ABSTRACT FROM AUTHOR]

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen-gene metabolic signature was developed to divide patients into a high-risk group and a low-risk group. Patients in the high-risk group presented poorer prognosis compared to the low-risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism-related pathways. To sum up, our study described a novel seventeen-gene metabolic signature for prognostic prediction of colon cancer. [ABSTRACT FROM AUTHOR]

Background. The choice of optimal treatment strategies for T4b colon cancers has still been discussed, particularly the initiation of neoadjuvant therapy or surgery. We conducted this study to evaluate the safety and feasibility of laparoscopic multivisceral resection for T4b colon cancers. Methods. We used the retrospective design to include all 43 patients with T4b colon cancer at a university hospital in Vietnam from March 2017 to March 2019. All patients were followed 30 days after the surgery, and information about the day of the first flatus, length of hospital stay, iatrogenic complications, postoperative morbidity, mortality, and adjuvant chemotherapy was collected. Results. The mean operating time was 187 minutes (ranging from 80 to 310), the mean blood loss was 64.3 ml (5-200), and the conversion rate was 2.3%. The mean number of lymph nodes harvested was 15.5 (SD = 8.06), and 33 patients (76.7%) had at least 12 lymph nodes harvested. A total of 21 patients (48.8%) had lymph node metastases with a mean number of lymph node metastases of 1.89 (SD = 3.4). The radial resection margin was R0 in all 43 patients (100%). The median time until the first flatus and hospital stay were 3 days (2–5) and 7.1 (6–11) days, respectively. There was no mortality at 30 days postoperatively, and one patient had iatrogenic complication (2.3%). Conclusion. Laparoscopic radical colectomy was feasible and safe for patients with T4b colon cancer except those requiring major and complicated reconstruction. [ABSTRACT FROM AUTHOR]

One of the deadliest diseases which affects the large intestine is colon cancer. Older adults are typically affected by colon cancer though it can happen at any age. It generally starts as small benign growth of cells that forms on the inside of the colon, and later, it develops into cancer. Due to the propagation of somatic alterations that affects the gene expression, colon cancer is caused. A standardized format for assessing the expression levels of thousands of genes is provided by the DNA microarray technology. The tumors of various anatomical regions can be distinguished by the patterns of gene expression in microarray technology. As the microarray data is too huge to process due to the curse of dimensionality problem, an amalgamated approach of utilizing bilevel feature selection techniques is proposed in this paper. In the first level, the genes or the features are dimensionally reduced with the help of Multivariate Minimum Redundancy–Maximum Relevance (MRMR) technique. Then, in the second level, six optimization techniques are utilized in this work for selecting the best genes or features before proceeding to classification process. The optimization techniques considered in this work are Invasive Weed Optimization (IWO), Teaching Learning-Based Optimization (TLBO), League Championship Optimization (LCO), Beetle Antennae Search Optimization (BASO), Crow Search Optimization (CSO), and Fruit Fly Optimization (FFO). Finally, it is classified with five suitable classifiers, and the best results show when IWO is utilized with MRMR, and then classified with Quadratic Discriminant Analysis (QDA), a classification accuracy of 99.16% is obtained. [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer (CRC) is an underlying deadly malignancy with poor prognosis, lacking effective therapies currently available to improve the prognosis. C18H17NO6 (AUCAN), a kind of dibenzofuran extracted from a special plant in Yunnan Province (China), is identified as a natural anticancer agent exerting strong inhibitory activities on various cancers. Our study was committed to investigating the potency of AUCAN against colorectal cancers and further exploring the potential mechanisms via proteomic analysis. Methods. Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate the effect of AUCAN on the viability and proliferation of HCT-116 cells and RKO cells. The apoptosis of HCT-116 and RKO cells after AUCAN administration was determined by the flow cytometry test. The effects of AUCAN on invasion and migration of tumor cells were investigated by the colony formation assay, wound healing test, and Transwell invasion test. Meanwhile, the energy metabolism and growth of tumor tissues after AUCAN administration with 10 mg/kg and 20 mg/kg were examined by PET-CT in vivo. The side effects of AUCAN treatment were also evaluated through blood routine and liver function examination. RKO cell proliferation and apoptosis in vivo were further determined by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry. Furthermore, the differentially expressed proteins (DEPs) involved in AUCAN treatment were determined by proteomic analysis followed by functional clustering analysis. Results. The results showed that AUCAN suppressed the migratory abilities and enhanced apoptosis of HCT-116 and RKO cell lines. Meanwhile, AUCAN treatment dramatically depressed the growth and volume of colorectal tumors in nude mice and suppressed the survival of RKO cells in tumor tissues without any side effects on the blood routine and liver function. In addition, twenty-four upregulated and forty-two downregulated proteins were identified. Additionally, functional clustering analysis concealed enriched biological processes, cellular components, molecular functions, and related pathways of these proteins involved in cellular metabolic. Finally, the protein-protein interaction analysis revealed the regulatory connection among these DEPs. Conclusions. Taken together, AUCAN exerted its significant antitumor effect without side effects in the blood routine and liver function and the underlying mechanisms were preliminarily investigated by proteomic analysis. [ABSTRACT FROM AUTHOR]