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Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Wang, Feng, Xue, Liang, Wu, Tan, Zhang, Zhang, Li and Zhang.)

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness., (© 2024. The Author(s).)

Background and Aim: The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN)., Methods: Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49., Results: We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49., Conclusions: Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel-related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals aged 60-74., Methods: A retrospective study was conducted on the high-risk individuals aged 60-74 participating in the 2021 CRC screening program in Tianjin, China. Logistic regression analyses, including both univariate and multivariate analyses, were performed to explore the impact of different risk factors on colonoscopy compliance among the high-risk individuals. Besides, the study investigated the influence of various risk factors on the detection rates of bowel-related diseases among the high-risk individuals who underwent colonoscopy., Results: A total of 24,064 high-risk individuals were included, and 5478 individuals received a free colonoscopy, with an overall compliance of 22.76%. Among them, the adenoma detection rate was 55.46%. Males and individuals with a positive FIT had high compliance and detection rates for CRC, advanced adenomas (AA), advanced colorectal neoplasia (ACN), and colorectal neoplasm (CN). Individuals aged 70-74 were associated with low compliance but high CRC, ACN, and CN detection rates. Individuals who reported a history of chronic constipation, bloody mucous, and CRC in first-degree relative showed high compliance but no significantwere associated with the detection rates of CRC, AA, and CN., Conclusion: This study reported several risk factors associated with the screening behaviors for CRC. Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the effectiveness of fecal immunochemical testing (FIT) in colorectal cancer screening., Methods: We conducted a prospective cohort study among 5,598 participants age 40-74 years between 2012 and 2020 in Tianjin, China. Inverse probability weighting was adopted to adjust for potential imbalanced factors between groups. A Cox proportional hazards model was used to estimate the weighted associations between FIT screening and advanced colorectal neoplasia. A difference-in-difference (DID) model was adopted to compare the incidence rates of advanced colorectal neoplasia between groups., Results: In DID analysis, the rate of incidence was reduced by 0.34 cases per person-years in the screening group as compared with the historical FIT screening group (rate ratio [RR], 0.08 [95% CI, 0.07 to 0.10]) and by 0.06 cases per person-years in the non-FIT screening group as compared with the historical non-FIT screening group (RR, 0.37 [95% CI, 0.29 to 0.48]; P < .001 for both comparisons), with a relative reduction of 0.28. Similar benefit effect from FIT screening was observed in sex and age subgroups., Conclusion: FIT screening was associated with a reduction in incidence density from advanced colorectal neoplasia.

Purpose: Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia., Patients and Methods: This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy., Results: A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years., Conclusions: These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy., (© 2023. The Author(s).)

The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor., (© 2023. Italian Society of Surgery (SIC).)

Background: H2.0-like homeobox ( HLX ) is highly expressed in several hematopoietic malignancies. However, the role of HLX in the carcinogenesis and progression of colorectal cancer (CRC) patients has rarely been reported., Methods: In this study, the data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The diagnostic value of HLX was analyzed by the R package "pROC." The overall survival was estimated using the "survival" and "survminer" packages. A nomogram was established to predict 1-, 3-, and 5-year overall survival of CRC patients. The CIBERSORT software was employed to calculate the relative proportions of 22 immune cells., Results: HLX expression was downregulated in CRC patients. Remarkably, HLX expression was increased with stage (stage I-stage III) of CRC, and the CRC patients with high HLX expression exhibited a poor prognosis. The promoter methylation level of HLX was prominently increased in CRC samples compared to paracancerous samples. We also found that the six miRNAs target HLX genes, leading to its downregulation, and HLX expression had a negative correlation with its downstream target gene BRI3BP in both CRC and normal samples. Finally, we found that the 12 immune infiltrating cells were observably different between high and low HLX expression groups. The HLX had a significant positive correlation with 8 immune checkpoints (PD-1 (PDCD1), CTLA4, PDL-1 (CD274), PDL-2 (PDCD1LG2), CD80, CD86, LAG3, and TIGIT) expressions., Conclusion: HLX probably played a carcinostasis role in the early stages of CRC but exhibited a cancer-promoting effect in the advanced stages. Meanwhile, HLX could serve as a reliable prognostic indicator for CRC., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this article., (Copyright © 2023 Shuo Chen et al.)

Background: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age., Methods: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age., Results: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40-49, 50-59, 60-69, and ≥ 70 age groups, respectively., Conclusions: The FIT detected ANs with highest accuracy in the 40-49 age group. Our research can provide guidance to formulate CRC screening strategies., (© 2023. The Author(s).)

Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing β-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.

Background and Aims: Colonoscopy is an important colorectal cancer (CRC) screening modality; however, not all high-risk groups identified by fecal immunochemical test (FIT) and/or high-risk factor questionnaire (HRFQ) undergo colonoscopy in time. The impact of delays in colonoscopy on CRC detection among high-risk populations remains poorly understood, warranting further clarification., Methods: A retrospective study was conducted among CRC high-risk population identified by Tianjin CRC screening program. According to the colonoscopy results after HRFQ and FIT, patients were classified into CRC, advanced adenoma, non-advanced adenoma, and normal groups. The time interval between CRC screening and colonoscopy was investigated and its relationship with colonoscopy results. Logistic regression was performed to explore the risk factors of CRC detection., Results: Among the high-risk population without a history of CRC or polyps, 49,810 underwent HRFQ, FIT, and colonoscopy, and a time interval of fewer than 6 months was found for 79.56% of patients (n = 39,630). People with positive FIT were more likely to undergo colonoscopy within 6 months, and detection rates of CRC and/or advanced adenoma were positively related to time intervals. Similar results were found in people with a negative FIT but positive HRFQ. A time interval longer than 6 months was a significant predictor of CRC detection in high-risk populations., Conclusion: For high-risk people identified by CRC screening, especially those with a positive FIT, a time interval of 6 months was associated with an increased probability of CRC detection. Our findings emphasize that populations at high risk should undergo colonoscopy at least within 6 months., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: Both the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites., Methods: We extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites., Results: The numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males., Conclusions: We observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender., (© 2023. The Author(s).)

Introduction: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients., Methods: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed., Results: The OS rate was 77.1% for young and 74.2% for older patients (P = 0.348). Landmark analysis showed a significant difference in survival between young and older patients, with 63.8% of deaths among young patients being within 25 months of surgery compared with 42.4% among older patients (P = 0.002). Among those who survived more than 25 months, young patients had significantly better survival than older patients (P = 0.009). Multivariable analysis of young patients revealed that the tumor location, perineural invasion, and stage were associated with poor survival within 25 months; after this period, stage was the only prognostic marker. Young patients were more likely to receive chemotherapy, particularly multiagent regimens. For young patients, no significant difference in OS was found based on the chemotherapy regimen, regardless of disease stage (II, III, or IV, all P > 0.05). In addition, unlike in older patients, no difference in OS was found in young patients regardless of the drug regimen administered (all P > 0.05)., Discussion: Young-onset CRC may have a unique disease biology that warrants further research and therapy development., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Given the limited effectiveness of the current Chinese colorectal cancer (CRC) screening procedure, adherence to colonoscopy remains low. We aim to develop and validate a scoring system based on individuals who were identified as having a high risk in initial CRC screening to achieve more efficient risk stratification and improve adherence to colonoscopy., Methods: A total of 29,504 screening participants with positive High-Risk Factor Questionnaire (HRFQ) or faecal immunochemical test (FIT) who underwent colonoscopy in Tianjin from 2012-2020 were enrolled in this study. Binary regression analysis was used to evaluate the association between risk factors and advanced colorectal neoplasia. Internal validation was also used to assess the performance of the scoring system., Results: Male sex, older age (age ≥ 50 years), high body mass index (BMI ≥ 28 kg/m 2 ), current or past smoking and weekly alcohol intake were identified as risk factors for advanced colorectal neoplasm. The odds ratios (ORs) for significant variables were applied to construct the risk score ranging from 0-11: LR, low risk (score 0-3); MR, moderate risk (score 4-6); and HR, high risk (score 7-11). Compared with subjects with LR, those with MR and HR had ORs of 2.47 (95% confidence interval, 2.09-2.93) and 4.59 (95% confidence interval, 3.86-5.44), respectively. The scoring model showed an outstanding discriminatory capacity with a c-statistic of 0.64 (95% confidence interval, 0.63-0.65)., Conclusions: Our results showed that the established scoring system could identify very high-risk populations with colorectal neoplasia. Combining this risk score with current Chinese screening methods may improve the effectiveness of CRC screening and adherence to colonoscopy., (© 2022. The Author(s).)

Background:  Screening recommendations for colorectal cancer (CRC) are mainly based on family history rather than lifestyle risk factors. We aimed to assess and compare risk factors for colorectal neoplasm (CRN) and evaluate trends in neoplasm detection rates during the three rounds of screening from 2012 to 2020 in Tianjin, China., Methods: This study was based on 89,535 first-recorded colonoscopies in Tianjin CRC screening program, 2012-2020. Of these, 45,380 individuals with complete family history and lifestyle factors were included for population attributable fraction (PAF) estimation., Results:  The overall detection rate of nonadvanced adenomas, advanced adenomas and CRC was 39.3%, 5.9% and 1.5%, respectively. The PAFs of current smoking, alcohol consumption, physical activity, higher BMI and family history of CRC, respectively, were 8.9%, 2.6%, 1.9%, 5.8%, and 1.1% for males with nonadvanced CRN; 12.3%, 7.3%, 4.9%, 7.2%, and 0.8% for males with advanced CRN; 3.4%, 0.4%, 2.1%, 7.8%, and 0.7% for females with nonadvanced CRN; and 4.3%, 0.2%, 8.2%, 8.5%, and -0.6% for females with advanced CRN. The PAFs of selected lifestyle factors were 19.9% for males with nonadvanced CRN, 29.0% for males with advanced CRN, 9.7% for females with nonadvanced CRN and 13.8% for females with advanced CRN., Conclusions:  Modifiable lifestyle factors, including smoking, alcohol consumption, physical activity and BMI, have a larger contribution to CRN than family history of CRC. Our findings will provide references for developing guidelines of CRC prevention and control in China., (© 2022. The Author(s).)

Background: This study aimed to develop an artificial intelligence predictive model for predicting the probability of developing BM in CRC patients., Methods: From SEER database, 50,566 CRC patients were identified between January 2015 and December 2019 without missing data. SVM and LR models were trained and tested on the dataset. Accuracy, area under the curve (AUC), and IDI were used to evaluate and compare the models., Results: For bone metastases in the entire cohort, SVM model with poly as kernel function presents the best performance, whose accuracy is 0.908, recall is 0.838, and AUC is 0.926, outperforming LR model. The top three most important factors affecting the model's prediction of BM include extraosseous metastases (EM), CEA, and size., Conclusion: Our study developed an SVM model with poly as kernel function for predicting BM in CRC patients. SVM model could improve personalized clinical decision-making, help rationalize the bone metastasis screening process, and reduce the burden on healthcare systems and patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Huang, Zhang, Zhang, Jing, Sun, Zhang, Lu and Zhang.)

BACKGROUND We aimed to evaluate the ability of circulating cell-free methylated SETP9 DNA (mSEPT9) to identify recurrence and to determine its clinical utility in adjuvant chemotherapy (ACT) regimen decisions. MATERIAL AND METHODS This study enrolled 426 patients with stage II-III CRC who received radical resection between January 8, 2018, and November 30, 2020. The median follow-up duration was 15.8 months (range, 8.1-43.4 months). The primary endpoint was recurrence-free survival (RFS). A propensity score matching model was used to minimize potential confounding covariates and to confirm our findings. RESULTS In stage II-III CRC patients, postoperative (within 1 month after surgery) mSEPT9 positivity was significantly correlated with worse RFS (HR=6.21, P<0.001), and it remained the strongest independent predictor in multivariate Cox regression analysis (HR=5.83, P<0.001), which was significantly superior to CEA, CA19-9, and CA242. During disease surveillance, mSEPT9 positivity preceded radiographic recurrence by a median of 5.0 months. The postoperative mSEPT9-positive patients benefited more from CAPEOX compared to FOLFOX (HR=3.97, P=0.017), while for mSEPT9-negative patients, CAPEOX and FOLFOX resulted in similar RFS (HR=1.70, P=0.322). Furthermore, 3 months of CAPEOX was more effective than 3 and 6 months of FOLFOX (HR=4.40, P=0.065; HR=1.56, P=0.073, respectively). CONCLUSIONS Our results revealed that mSEPT9 detection after radical resection could identify minimal residual disease (MRD) and could predict a high risk of recurrence in patients with stage II-III CRC. Furthermore, we show pioneering work that mSEPT9 detection could be used to guide the selection of an adjuvant chemotherapy regimen to improve RFS.

The mutation status of the gene involved in early colorectal carcinogenesis and micro-invasive liquid biopsy allows detection of mutated circulating tumor DNA (ctDNA). Early detection of precancerous lesions and CRC is vital in proper treatment and hence associated to patient survival. The frequency of APC, CTNNB1, KRAS, and BRAF mutations in circulating free DNA (cfDNA) were analyzed to evaluate the performance of the mutated ctDNA in detecting polyp and adenoma using highly sensitive QClamp XNA based PCR. A total of 71 patients with low-risk adenoma or polyps were screened and there was no significant difference in the distribution of mutations gender, age, long-term medication, smoking history, alcohol drinking, and fecal occult blood. The positive predictive value (PPV) of the four genes' panel to detect low-risk adenoma and polyps was 39.44% (n = 28/71). Specifically, of all the 71 cases studied, there were 20 cases (28.2%) with APC mutations, 7 cases (9.9%) with CTNNB1 mutations, 4 cases (5.6%) with KRAS mutations, and 2 cases (2.8%) with BRAF mutations. Most mutations occurred at APC876. The four genes' panel detected by XNA-based PCR technique might be suited to efficiently and micro-invasively detect genetic alterations in cfDNA of patients with precancerous colorectal lesions.

Background: Colorectal cancer (CRC) is a common human malignancy worldwide. The prognosis of patients is largely frustrated by delayed diagnosis or misdiagnosis. DNA methylation alterations have been previously proved to be involved in CRC carcinogenesis. Methods: In this study, we proposed to identify CRC-related diagnostic biomarkers by analyzing DNA methylation and gene expression profiles. TCGA-COAD datasets downloaded from the Cancer Genome Atlas (TCGA) were used as the training set to screen differential expression genes (DEGs) and methylation CpG sites (dmCpGs) in CRC samples. A logistic regression model was constructed based on hyper-methylated CpG sites which were located in downregulated genes for CRC diagnosis. Another two independent datasets from the Gene Expression Omnibus (GEO) were used as a testing set to evaluate the performance of the model in CRC diagnosis. Results: We found that CpG island methylator phenotype (CIMP) was a potential signature of poor prognosis by dividing CRC samples into CIMP and noCIMP groups based on a set of CpG sites with methylation standard deviation (sd) > 0.2 among CRC samples and low methylation levels (mean β < 0.05) in adjacent samples. Hyper-methylated CpGs tended to be more closed to CpG island (CGI) and transcription start site (TSS) relative to hypo-methylated CpGs ( p -value < 0.05, Fisher exact test). A logistic regression model was finally constructed based on two hyper-methylated CpGs, which had an area under receiver operating characteristic curve of 0.98 in the training set, and 0.85 and 0.95 in the two independent testing sets. Conclusions: In conclusion, our study identified promising DNA methylation biomarkers for CRC diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Yuan, Wang, Chen, Zhang and Zhang.)

Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies., (© 2020 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)

Colorectal cancer (CRC) is the third most common cancer worldwide. This study aimed to explore the regulatory mechanisms of miRNAs in CRC. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in CRC tissue samples compared with control samples in mRNA and miRNA datasets were screened. Functional and pathway enrichment analysis of the DEGs was carried out. Targets of the DEMs were identified. Overlaps between the DEGs and targets of DEMs were selected. The miRNA-mRNA regulatory network of these overlaps was constructed and visualized. The candidate genes selected were validated by quantitative real-time PCR. DEGs were identified and considered DEGs-1 and DEGs-2. A total of 584 genes in DEGs-1 and 527 genes in DEGs-2 were obtained, including 465 overlaps, and 44 DEMs were identified. The overlaps were enriched in 46 Gene Ontology terms and 19 Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, 137 overlapped genes between targets of the DEMs and the 465 overlaps were obtained. The miRNA-mRNA regulating network of the 137 overlapped genes was constructed. Extracellular matrix-related proteins and pathways might play critical roles in the development of CRC. The quantitative real-time PCR results of the candidates were in agreement with the bioinformatics analysis. miR-128, miR-182, and miR-143 might be key miRNAs regulating cell proliferation and metastasis of CRC.

Background: The application of circulating, cell-free, methylated Septin9 ( m SEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of m SEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring., Methods: For screening and diagnosis of CRC, peripheral m SEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of m SEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT)., Results: Seventy-three percent of CRC patients were m SEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were m SEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of m SEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of m SEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of m SEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR)., Conclusions: m SEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of m SEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR.

Long noncoding RNAs (lncRNAs) have recently emerged as important biomarkers of cancer progression. Here, we proposed to develop a lncRNA-based signature with a prognostic value for colorectal cancer (CRC) overall survival (OS). Through mining microarray datasets, we analyzed the lncRNA expression profiles of 122 patients with CRC from Gene Expression Omnibus. Associations between lncRNA and CRC OS were firstly evaluated through univariate Cox regression analysis. A random survival forest method was applied for further screening of the lncRNA signature, which resulted in eight lncRNAs, including PEG3-AS1, LOC100505715, MINCR, DBH-AS1, LINC00664, FAM224A, LOC642852, and LINC00662. Combination of the eight lncRNAs weighted by their multivariate Cox regression coefficients formed a prognostic signature, through which, we could divide the 122 patients with CRC into two subgroups with significantly different OS. Good robustness of the lncRNA signature's prognostic value was verified through an independent data set consisting of 55 patients with CRC. In addition, gene set enrichment analysis indicated the potential association between high prognostic value and oxygen metabolism-related processes. This result should indicate that lncRNAs could be a useful signature for CRC prognosis., (© 2018 Wiley Periodicals, Inc.)

The aim of the present study was to screen colorectal cancer (CRC) tissue and adjacent tissue for differences in circular RNA (circRNA) expression, to analyze the related miRNAs and messenger RNAs (mRNAs), and to investigate the circRNA expression in CRC and its function. The circRNA expression profile was generated using CapitalBio microarray technology. The differentially expressed circRNAs were identified with GeneSpring 12.5 software. Subsequently, the related mRNAs of the differentially expressed circRNAs were annotated with the molecule annotation system (MAS) 3.0, and the diseases, pathways and functional enrichment analysis of these mRNAs were performed using the KEGG orthology‑based annotation system (KOBAS) 3.0. In addition, the target miRNAs of differentially expressed circRNAs were screened using the miRanda algorithm. The circRNA/miRNA network was constructed for the top 8 most significant differentially expressed circRNAs with Cytoscape software 3.4.0. A total of 10,245 differentially expressed circRNAs were identified, including 6,264 upregulated ones, and 3,981 downregulated ones. The related mRNAs were enriched in 462 KEGG diseases, 411 FunDO, 669 NHGRI GWAS catalog, and 845 OMIM; and 1,334 Reactomes, 281 KEGG pathways, 117 PANTHER and 193 BioCyc; and 11,606 Gene Ontology (GO) terms. A total of 133 circRNA/miRNA pairs were involved in the circRNA/miRNA network. hsa&#95;circ&#95;0126897&#95;CBC1 may be a potential biomarker for CRC, and the cell cycle was closely associated with the occurrence and development of CRC.

MicroRNAs (miRNAs) are small non‑coding RNAs, which are critical in a diverse range of biological processes, including development, differentiation, homeostasis, and in the formation of diseases by accelerating and/or inhibiting the translation of mRNAs. The present study aimed to examine the potential role of miRNA (miR)‑205‑5p in the developmental process of colorectal cancer (CRC) through protein‑tyrosine kinase 7 (PTK7). Initially, TargetScan was used to predict the miRNA target sites in the sequence of the PTK7 3'‑untranslated region. It was then found that the mRNA expression level of miR‑205‑5p was lower in CRC cells, determined using reverse transcription‑quantitative polymerase chain reaction analysis, and there was a negative correlation between miR‑205‑5p and PTK7 in CRC tissues. It was also found that miR‑205‑5p regulated the gene transcription of PTK7, determined using a luciferase reporter assay. The results of RT‑qPCR and western blot analyses in human colorectal cancer revealed that miR‑205‑5p suppressed the expression of PTK7. Finally, it was revealed that miR‑205‑5p restricted the proliferation ability of CRC cells through inhibiting PTK7, which was determined using colony forming and 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assays. miR‑205‑5p accelerated cell apoptosis through inhibiting PTK7, demonstrated using Annexin V‑FITC/propidium iodide staining. The results of a Transwell assay indicated that miR‑205‑5p inhibited the migration and invasion abilities of CRC cells through inhibiting PTK7. Therefore, miR‑205‑5p is involved in the proliferation, migration and invasion of CRC through inhibiting PTK7.

BACKGROUND The aim of this study was to screen the molecular targets of miR-34a in colorectal cancer (CRC) and construct the regulatory network, to gain more insights to the pathogenesis of CRC. MATERIAL AND METHODS The microarray data of CRC samples and normal samples (GSE4988), as well as CRC samples transformed with miR-34a and non-transfected CRC samples (GSE7754), were downloaded from the Gene Expression Omnibus (GEO) database. The differently expressed genes (DEGs) were identified via the LIMMA package in R language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to identify significant Gene Ontology (GO) terms and pathways in DEGs. The targets of miR-34a were obtained via the miRWalk database, and then the overlaps between them were selected out to construct the regulatory network of miR-34a in CRC using the Cytoscape software. RESULTS A total of 392 DEGs were identified in CRC samples compared with normal samples, including 239 upregulated genes and 153 downregulated ones. These DEGs were enriched in 75 GO terms and one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. At the same time, 332 DEGs (188 upregulated and 144 downregulated) were screened out between miR-34a transformed CRC and miR-34a non-transfected CRC samples and they were enriched in 20 GO terms and eight KEGG pathways. Six overlapped genes were identified in two DEGs groups. There were 1,668 targets of miR-34a obtained via the miRWalk database, among which 21 were identified differently expressed in miR-34a transformed CRC samples compared with miR-34a non-transfected CRC samples. Two regulatory networks of miR-34a in CRC within these two groups of overlapped genes were constructed respectively. CONCLUSIONS Pathways related to cell cycle, DNA replication, oocyte meiosis, and pyrimidine metabolism might play critical roles in the progression of CRC. Several genes such as SERPINE1, KLF4, SEMA4B, PPARG, CDC45, and KIAA0101 might be the targets of miR-34a and the potential therapeutic targets of CRC.

A genome-wide association study identified a common genetic variant rs4939827 at 18q21 in SMAD7 to be related with colorectal cancer (CRC) risk with OR=1.2 and P =7.80E-28. Until recently, several meta-analysis studies have been conducted, and reported significant association between rs4939827 and CRC risk. However none of these studies evaluated the potential association between rs4939827 and CRC risk in Chinese population. In this study, we evaluated this association by a meta-analysis using 12077 samples including 5816 CRC cases and 6261 controls. In the end, we identified the T allele of rs4939827 to be significantly related with an increase CRC risk (P=2.22E-05, OR=1.14, 95% CI 1.07-1.21) in Chinese population.

Rectal cancer is a common malignant tumor of the digestive tract, with a high incidence and high mortality. This study aimed to identify the potential biomarkers and therapeutic targets for rectal adenocarcinoma (RAC) metastasis. The expression profiling of RAC patients with metastasis and RAC patients without metastasis was downloaded from The Cancer Genome Atlas (TCGA) database. The datasets were used to identify the genes associated with RAC metastasis. Fifty up-regulated genes and seventeen down-regulated genes were identified in the primary tumor loci of RAC metastasis compared with non-metastasis. Sixty-seven dysregulated gens were conducted to construct the protein-protein network, and CCND3 was the hub protein. The dysregulated genes were significantly enriched in pancreatic secretion, cell adhesion molecules pathways, response to vitamin D of biological process, and retinoid binding of molecular function. Quantitative real-time polymerase chain reaction results demonstrated that CCND3, AQP3, PEG10, and RAB27B had the up-regulated tendency in RAC metastasis; ADCY1 had the down-regulated tendency in RAC metastasis. CCND3, AQP3, PEG10, RAB27B, and ADCY1 might play essential roles in the metastasis process of RAC through pancreatic secretion and cell adhesion molecules pathways. The five genes could be potential diagnosis biomarkers or therapeutic targets for RAC metastasis., (© 2016 APMIS. Published by John Wiley & Sons Ltd.)

Objective: The aim of this retrospectively study was to evaluate the clinical efficacy of Aidi injection (ADI) combined with FOLFOX4 chemothreapy regimen in the treatment of advanced colorectal carcinoma., Patients and Methods: One hundred and twenty one patients with pathology confirmed advanced colorectal carcinoma were retrospectively analyzed in the department of colorectal surgery in Union Medical Center, Tianjin (UMC). Of the included 121 cases, 58 subjects received the treatment of ADI combined with FOLFOX4 chemotherapy (experiment group) and the other 63 cases received the FOLFOX4 chemotherapy alone (control group). After two cycles chemotherapy treatment, the short-term clinical efficacy such as complete response (CR), partial response (PR) and objective response rate (ORR) were compared between the two groups. The quality of life improvement and chemotherapy related toxicity were also recorded and analyzed., Results: The response rate including CR, PR and ORR were not statistical different between the experiment group and control group (P > 0.05); The KPS score was significant decrease in the control group compared to that in experiment group (P < 0.05); The risk of developing grade-II nausea vomiting and diarrhea was much lower in experiment than that in control group (Pall < 0.05)., Conclusion: ADI combined with FOLFOX4 chemotherapy can improve the quality of life and decrease some of the toxicity related to chemotherapy in patients with advanced colorectal cancer.

Objective: the aim of this study was to determine the clinicopathological characteristics of colorectal cancer (CRC) patients complicated with type 2 diabetes mellitus (T2DM )., Methods: A total of 3, 202 patients with CRC confirmed pathologically in Tianjin Union Medicine Center from January 2005 to December 2009 were included in this study. We analyzed the differences in clinicopathological features between T2DM patients and non-diabetic patients according to age of diagnosis, gender, tumor site, stage, gross type, histological type, and differentiation., Results: From 2005 to 2009, the number of CRC patients increased yearly. The high incidence age of all CRC patients was 51 to 80 years old. The male to female ratio was 1.18:1, showing that the number of female patients with CRC was increased significantly compared with males. The CRC distribution of T2DM patients and non-diabetic patients showed a predominance of rectal cancer (64.4%, 68.7%), followed by sigmoid colon cancer (12.5%, 13.0%), and moderately differentiated ulcer-type adenocarcinoma. Compared with non-diabetic patients, T2DM patients were older (66.2 years versus 62.7 years, P < 0.001) and had more multiple CRCs (3.5% versus 1.6%, P < 0.001). Moreover, the proportion of lymph node or organ metastasis in T2DM patients was higher than that in non-diabetic patients (52.6% versus 45.6%, P < 0.05). No significant differences were observed between both groups in terms of gender, gross type, histological type, and differentiation(P > 0.05 for all)., Conclusions: CRC incidence shows an increasing trend with age. CRC patients with T2DM have an older age of onset, higher proportion of lymph node and distant organ metastasis than in non-diabetic patients.

Purpose: MGb2, a mouse-derived monoclonal antibody specific to gastric carcinoma, was developed in our laboratory. Nevertheless, the potential role of MGb2-antigen/TRAK1 (MGb2-Ag/TRAK1) in colorectal cancer (CRC) is unclear. The aim of this study was to investigate the relationship between MGb2-Ag/TRAK1 expression and the clinicopathological characteristics of CRC. The potential utility of MGb2-Ag/TRAK1 expression as a prognostic indicator was also evaluated., Methods: Immunohistochemistry and western blot were used to detect MGb2-Ag/TRAK1 expression in 140 CRC tissues. The relationship between MGb2-Ag/TRAK1 expression and clinicopathological characteristics and postoperative survival time was statistically analyzed., Results: MGb2-Ag/TRAK1 expression in CRC tissues was significantly higher than in normal tissues and was positively correlated with tumor differentiation (p = 0.006), invasion (p = 0.049), and pathological stage (p = 0.032). There was no significant difference between MGb2-Ag/TRAK1 expression and the age or gender of the patient, lymphatic invasion, or distant metastasis (p = 0.586, 0.308, 0.910, and 0.068, respectively). The survival time of CRC patients with high expression of MGb2-Ag/TRAK1 was shorter than the survival time of patients with low MGb2-Ag/TRAK1 expression. Both univariate and multivariate analyses showed that tumor differentiation and MGb2-Ag/TRAK1 expression were two independent and prognostic factors for CRC (p < 0.001)., Conclusions: MGb2-Ag/TRAK1 may play an important role in the development of CRC and may be a valuable prognostic indicator of CRC.

MC3 and MC5 are both colorectal cancer-specific MAbs previously prepared in our laboratory that can detect colorectal cancer with high sensitivity and specificity. Thus far the distribution of MC3-Ag and MC5-Ag in colorectal cancer remains largely unknown. In the present study, we have firstly found that the expression of MC3-Ag and MC5-Ag was higher in moderate-differentiated and poor-differentiated colorectal cancer tissue than that in well-differentiated colorectal cancer tissue by immunohistochemistry. The expression of MC5-Ag in colorectal cancer tissue without metastasis was found to be significantly less than that in tissue accompanied with metastasis. However, the expression of MC3-Ag in colorectal cancer tissue without metastasis was found similar to that in tissue accompanied with metastasis. The results showed that MC3-Ag and MC5-Ag might play important roles in colorectal carcinogenesis and that MC3 and MC5 could be used as a tool for screening colorectal cancer.