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Simple Summary: The peritoneum, a common metastatic site of colorectal cancer (CRC), has a high incidence and poor prognosis that makes it difficult to diagnose early. Peritoneal metastasis (PM) depends on the synergistic action of multiple molecules and the regulation of various components of the tumor microenvironment. A multidisciplinary combination approach is still recommended for treating the disease currently. Cytoreductive surgery (CRS) combined with intraperitoneal chemotherapy (IPC) may benefit patients with CRC-PM, but further clinical trials and higher-level evidence-based medical evidence are needed. Peritoneal metastasis (PM) is a common mode of distant metastasis in colorectal cancer (CRC) and has a poorer prognosis compared to other metastatic sites. The formation of PM foci depends on the synergistic effect of multiple molecules and the modulation of various components of the tumor microenvironment. The current treatment of CRC-PM is based on systemic chemotherapy. However, recent developments in local therapeutic modalities, such as cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC), have improved the survival of these patients. This article reviews the research progress on the mechanism, characteristics, diagnosis, and treatment strategies of CRC-PM, and discusses the current challenges, so as to deepen the understanding of CRC-PM among clinicians. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammation is closely associated with the initiation and development of tumors. Based on the counts of peripheral neutrophils, monocytes and lymphocytes, we established a new systemic inflammation response index (SIRI) to predict postoperative survival of patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 916 ESCC patients treated with radical esophagectomy were enrolled in the present study. Results Survival analysis indicated that the median overall survival (OS) in patients with SIRI≤1.2 was significantly higher than that in patients with SIRI>1.2. The nomogram including SIRI could more accurately predict OS compared with the TNM staging system. In addition, the changes of SIRI from baseline to 8 weeks after the operation were correlated with patient survival. The patients with an increase in SIRI >75% had worse OS compared with those with no change, while the patients with a decrease in SIRI >75% or in the scope of 25% ~75% exhibited better OS. Conclusions SIRI was an independent prognostic index of ESCC patients after the radical resection. The nomogram integrating the SIRI could help clinicians to screen the high-risk patients and formulate the individualized treatment schemes. Highlights • The SIRI was identified to be an independent prognostic factor for ESCC. • The nomogram based on SIRI can efficiently predict the prognosis of ESCC patients. • The changes of SIRI from baseline to 8 weeks were correlated with patient survival. [ABSTRACT FROM AUTHOR]

Background/Aims: The role of Tumor-infiltrating lymphocytes (TILs) in the prognosis of patients with lung cancer is still controversial. We performed a meta-analysis to evaluate the prognostic role of TILs in lung cancer. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library and assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the association between TIL subsets and lung cancer patients' outcome. Results: A total of 29 articles including 8,600 patients were enrolled into the meta-analysis. Our results indicated that high level of CD8+ cells infiltration in tumor stroma (TS) or tumor nest (TN) was associated with better OS in lung cancer patients (HR = 0.76, 95% CI 0.62-0.93, P = 0.006; HR = 0.80, 95% CI 0.67-0.96; P = 0.018, respectively). Similar results could be also observed in CD3+ T cells infiltration. High CD4+ T lymphocytes infiltration in TS was explicitly accompanied by better OS (HR = 0.65, 95% CI 0.46-0.91; P = 0.013), rather than in TN. In contrast, high density of FOXP3+ T cells infiltration in TS showed a poor PFS (HR = 2.67, 95% CI, 1.74-4.08, P < 0.001). Conclusion: This meta-analysis clarified that high level of CD8+ and CD3+ T cells infiltration in TS or TN, and high CD4+ T lymphocytes infiltration in TS showed better OS in lung cancer patients, whereas high density of FOXP3+ T cells infiltration in TS could be recognized as a negative prognostic factor. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. Results: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. Conclusion: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: We conducted this study to evaluate the expression of leptin and its receptor, OB-Rb in gastric cancer and their relationship to clinicopathological features, VEGF and HER-2 expression, as well as the prognostic value. One hundred and ten gastric cancer specimens were detected for leptin, OB-Rb, VEGF and HER-2 by immunohistochemistry (IHC), and 96 specimens of normal gastric mucosa served as the control. The expression level of leptin, OB-Rb and HER-2 in gastric tissues were significantly higher than normal tissues (49.1% vs. 34.0%, 60.9% vs. 46.0%, 19.1% vs. 8.0%, P <0.05). There was a correlation between the expression of leptin and HER-2, both of which were significantly associated with invasion depth, lymph node metastasis, AJCC stage and VEGF expression. However, there was no correlation between OB-Rb expression and all clinicopathological features. Cox regression analyses showed that age, tumor size, histological grade, serosa invasion, AJCC stage, chemotherapy, leptin and HER-2 overexpression were prognostic factors. The survival of patients with leptin positive expression was significantly poorer than those with negative expression (OS: 20.0months vs. 32.5months, FPS: 12.0months vs. 18.0months, P <0.01). Leptin, rather than OB-Rb, played an important role in the progression and angiogenesis of gastric cancer, and was a prognostic factor for poor outcome. [Copyright &y& Elsevier]

Abstract: Objective: To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods: Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results: None of the patients achieved a complete response (CR), while 15 patients achieved a partial remission (PR) and 17 experienced a stable disease (SD). Thirteen patients continued to have a progressive disease (PD). The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash (53.3%) and diarrhea (33.3%). Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion: Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients. [Copyright &y& Elsevier]

Systemic immune-inflammation index (SII), based on peripheral lymphocyte, neutrophil, and platelet counts, was recently investigated as a prognostic marker in several tumors. However, SII has not been reported in esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic value of the SII in 916 patients with ESCC who underwent radical surgery. Univariate and multivariate analyses were calculated by the Cox proportional hazards regression model. The time-dependent receiver operating characteristics (ROC) curve was used to compare the discrimination ability for OS. PSM (propensity score matching) was carried out to imbalance the baseline characteristics. Our results showed that SII, PLR, NLR and MLR were all associated with OS in ESCC patients in the Kaplan-Meier survival analysis. However, only SII was an independent risk factor for OS (HR = 1.24, 95% CI 1.01-1.53, P = 0.042) among these systemic inflammation scores. The AUC for SII was bigger than PLR, NLR and MLR. In the PSM analysis, SII still remained an independent predictor for OS (HR = 1.30, CI 1.05-1.60, P = 0.018). SII is a novel, simple and inexpensive prognostic predictor for patients with ESCC undergoing radical esophagectomy. The prognostic value of SII is superior to PLR, NLR and MLR. [ABSTRACT FROM AUTHOR]

Abstract: Purposes: This study was conducted to assess the efficacy and toxicity of gefitinib as first line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve patients with advanced (stage IIIB, IV and recurrent) NSCLC. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20 and 21. Sixty-one patients received 250mg of gefitinib daily until disease progression or unacceptable toxicity. Results: Out of 61 patients, 26 patients (42.6%) were EGFR mutations and 11 patients were wild type, 24 patients were status unknown. One patient achieved complete remission (CR). While 17 patients achieved partial remission (PR) and 23 experienced stable disease (SD). There were 20 patients developed progressive disease (PD). The tumor response rate and disease control rate was 29.5 and 67.2%, respectively, and symptom remission rate was 66.7% as well. Median remission time was 9 days. Median over survival time was 13.0 months. Median progression-free survival time was 5.0 months. The MST of patients with EGFR mutation was 17.0 months, while the MST of patients with EGFR status unknown or wild type was 11.0 months. The PFS of patients with EGFR mutation was 9.0 months and it in EGFR status unknown or wild type was 2.5 months .The most common toxicity included rash (54.1%) and diarrhea (31.1%). Dehydration and pruritus of skin was observed in 31.1 and 26.2% of the patients respectively. Hepatic toxicity occurred in 8.2% of patients and oral ulceration occurred in six patients (9.8%). Conclusion: Single agent treatment with gefitinib is effective in patients with advanced NSCLC, especially in patients with EGFR mutation, and well tolerated in Chinese patients. [Copyright &y& Elsevier]

Epidermal growth factor receptor (EGFR)-targeted therapy is an important treatment for RAS wild-type metastatic colorectal cancer (mCRC), but the resistance mechanism remains unclear. Here, the differential expression of circRNAs between Cetuximab sensitive and resistant cell lines was analyzed using whole-transcriptome sequencing. We identified that the expression of circHIF1A was significantly higher in LIM1215-R than in LIM1215. When treated with Cetuximab, downregulation of circHIF1A level weakened the proliferation and clonal formation ability of LIM1215-R, caused more cells to enter G0-G1 phase, and significantly reduced the basal respiration, ATP production, and maximal respiration, as well as the glycolytic capacity and glycolytic reserve. The response rate and prognosis of circHIF1A-positive patients were inferior to those of negative patients. Mechanistically, circHIF1A can upregulate the level of hypoxia-inducible factor 1 A (HIF1A) by competitively binding to miR-361-5p, inducing the overexpression of enzymes such as glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). In a xenograft model, inhibition of circHIF1A expression increased the sensitivity to Cetuximab treatment. In conclusion, circHIF1A can promote HIF1α-mediated glycometabolism alteration to induce Cetuximab resistance in CRC. It has the potential to become a screening indicator for the Cetuximab beneficial population in mCRC and a new therapeutic target for enhancing treatment efficacy., (© 2024. The Author(s).)

Background: Liver metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the precise mechanisms remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the cellular and molecular heterogeneity between CRC primary lesion and corresponding liver metastasis, and to clarify the characteristics of the tumor microenvironment (TME) in synchronous liver metastasis of CRC., Methods: A case of microsatellite stable (MSS) sigmoid carcinoma with synchronous liver metastasis was selected, and tissues from the primary tumor and the liver metastasis were collected for scRNA-seq. The EdgeR package software was used to identify the differentially expressed genes between cells. Gene Set Enrichment Analysis (GSEA) was performed and the clusterProfiler R package was used for Gene Ontology (GO) enrichment analysis. The SCENIC and CellphoneDB packages were used to reconstruct the transcriptional regulatory networks and to analyze the intercellular interaction network, respectively., Results: Compared to the primary tumor, the proportion of myeloid cells in the metastatic tumor was significantly increased, while B cells and plasma cells were decreased. In the metastatic tumor, the myeloid-derived suppressor cell (MDSC) characteristic gene, mannose receptor C-type 1 (MRC1) and tumor associated macrophage 2 (TAM2)-related gene, were highly expressed. Furthermore, angiogenesis, oxidative phosphorylation, and endothelial mesenchymal transition (EMT) of myeloid cells were also significantly enhanced. There were less myeloid cells in primary tumors, and these were mainly monocytes and TAM1; while the number of TAM2 was significantly upregulated in the metastatic samples. In liver metastasis, the T cell population was exhausted, and this was accompanied by a significant increase in the number of CD4 + T cells and a decrease in the number of CD8 + T cells. Furthermore, some immune checkpoint molecules were highly expressed. Interactions between myeloid cells and other cell populations appeared to be strong., Conclusions: The TME of CRC liver metastasis is significantly immunosuppressed. Interactions between myeloid cells and other cell populations in the TME contribute to the establishment of a pro-metastatic niche that promotes colonization and growth of CRC cells in the liver. TAMs may be a potential immunotherapeutic target for MSS CRC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5270/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The factors affecting the postoperative survival of patients with primary appendiceal cancer (PAC) have yet to be fully explored. And there are no clear guidelines for adjuvant treatment after appendectomy. Whether chemotherapy can prolong patient survival after appendectomy, is critical in guiding postoperative medications. The majority of studies on appendiceal cancer are single case reports, and they focused on the incidence of appendiceal cancer. The present study aimed to investigate the survival characteristics of patients with primary appendiceal cancer after surgery using the Surveillance, Epidemiology, and End Results (SEER) database., Methods: The data of 2,891 cases of primary appendiceal cancer between 2004 to 2015 were obtained from the SEER database and subjected to survival analysis using the Kaplan-Meier method and Cox proportional-hazards model. The annual percentage change (APC) was calculated using the weighted least squares method., Results: The overall age-adjusted incidence rate per 100,000 population steadily increased from 0.58 in 2004 to 1.63 in 2015. For patients who received chemotherapy, the median overall survival (OS) was 65 months and the 5-year OS rate was 51.9%, and for patients who did not receive chemotherapy or whose chemotherapy status was unknown, the median OS was not reached and the 5-year OS rate was 78.9%. Age [35< age <69: hazard radio (HR) =2.147; 95% confidence interval (CI): 1.442-3.197, P<0.001; age >69: HR =5.259; 95% CI: 3.485-7.937, P<0.001], race (White race: HR =0.728; 95% CI: 0.590-0.899, P=0.003), histologic type (mucinous neoplasm: HR =0.690; 95% CI: 0.580-0.821, P<0.001; malignant carcinoid: HR =0.657; 95% CI: 0.536-0.806, P<0.001), grade (II: HR =1.794; 95% CI: 1.471-2.187, P<0.001; III: HR =2.905; 95% CI: 2.318-3.640, P<0.001; IV: HR =3.128; 95% CI: 2.159-4.533, P<0.001), and stage (localized: HR =0.236; 95% CI: 0.194-0.287, P<0.001; regional: HR =0.425; 95% CI: 0.362-0.499, P<0.001) were identified as independent predictors of survival. And after adjusting for known factors (age, sex, race, tumor size, marital status, histologic type, grade, stage), chemotherapy (HR =1.220; 95% CI: 1.050-1.417, P=0.009) was revealed to be an independent indicator of poor prognosis., Conclusions: There was an increasing trend in the incidence of appendiceal cancer in the United States between 2004 and 2015. Chemotherapy was revealed to be an independent indicator of poor prognosis, which provide valuable insight into the therapy of primary appendiceal cancer. Large clinical trials of chemotherapy and targeted therapy for appendiceal cancer are urgently needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-454/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Circular RNA (circRNA) plays an important role in the development of human malignant tumors. Recently, an increasing number of circRNAs have been identified and investigated in various tumors. However, the expression pattern and biological function of circRNAs in colorectal cancer (CRC) still remain largely unexplored. In the present study, hsa&#95;circ&#95;0009361 was significantly down-regulated in CRC tissues and cells. Low expression level of hsa&#95;circ&#95;0009361 promoted the proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion of CRC cells. Hsa&#95;circ&#95;0009361 was identified as the sponge of miR-582 by fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays. Overexpression of hsa&#95;circ&#95;0009361 up-regulated the expression of adenomatous polyposis coli 2 (APC2) and inhibited the activity of the Wnt/β-catenin pathway by competitively combining with miR-582. Exogenous miR-582 and APC2 interventions could reverse the multiple biological functions mediated by hsa&#95;circ&#95;0009361 in CRC cells. In vivo experiments also confirmed that hsa&#95;circ&#95;0009361 inhibited the growth and metastasis of CRC. Hsa&#95;circ&#95;0009361 acted as a tumor suppressive sponge of miR-582, which could up-regulate the expression of APC2, inhibit the Wnt/β-catenin signaling, and suppress the growth and metastasis of CRC. Collectively, the hsa&#95;circ&#95;0009361/miR-582/APC2 network could be employed as a potential therapeutic target for CRC patients., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Long non-coding RNAs (lncRNAs) are implicated in many tumors. To find novel targets for study of diffuse large B-cell lymphoma (DLBCL), our team performed genome-wide analyses of lncRNA expression in 5 DLBCL cell lines using the 4*180K Agilent lncRNA Chip system, and in normal B cells. Five lncRNAs were validated by quantitative reverse transcription polymerase chain reaction. The differentially expressed lncRNAs and mRNAs were identified via false discovery rate and fold-change filtering. Potential targets correlated with DLBCL were recognized via gene ontology and pathway analysis. Establishment of the co-expression network was done using Cytoscape. In total, 1053 lncRNAs and 4391 mRNAs were dysregulated in DLBCL cells, being comparing with normal B cells. The results suggested that the expressions of the 5 lncRNAs were consistent with the chip results. Several terms including the cell cycle, apoptosis, B cell receptor and NF-κB signaling pathways were important in the progression of DLBCL. The chromosome locations of a few lncRNAs and the associated coexpressed genes were demonstrated by cis-regulatory gene analyses. The results of trans-analyses showed that multiple transcription factors regulated lncRNA and gene expression. Those outstanding lncRNAs in each group were implicated in the regulation of the TF-lncRNA-target gene network. Our study identified a set of lncRNAs differentially expressed in DLBCL cells.

Growing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors. This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamous cell carcinoma (ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores. We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve, and compared with the 6(th) and 7(th) AJCC TNM classifications. The neutrophil lymphocyte ratio (NLR), C-reactive protein albumin (CRP/Alb) ratio, histological grade, T stage and modified N stage were integrated in the nomogram. The C-index of the nomogram for predicting the survival was 0.72, which showed better predictive ability of OS than the 6(th) or 7(th) TNM stages in the primary cohort (P < 0.001). The calibration curve showed high consistency between the nomogram and actual observation. The decision curve analysis showed more potential of clinical application of the prediction models compared with TNM staging system. Moreover, our findings were supported by the validation cohort. The proposed nomogram showed more accurate prognostic prediction for patients with ESCC after radical esophagectomy.

Recently, many studies have shown that the B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) exhibits altered expression in various cancers and may serve as prognostic biomarkers. We performed a meta-analysis to evaluate the prognostic role of Bmi-1 expression in solid cancers. Studies were recruited by searching PubMed, Embase and the Cochrane Library. Thirty-nine articles including 40 studies were involved in this meta-analysis. Our results indicated that the Bmi-1 showed the opposite prognostic effect in Asian and Caucasian populations. High Bmi-1 expression as a negative predictor for overall survival (OS) in Asian patients (HR=1.96, 95% CI 1.62-2.36), but a positive predictor in Caucasian populations (HR=0.77, 95% CI 0.63-0.93). Furthermore, we took a further subgroup analysis based on tumor type in these two populations, respectively. In Asian cases, high expression of Bmi-1 was associated with poor OS in oesophageal carcinoma (HR=1.93, 95% CI 1.52-2.46), gastric cancer (HR=1.50, 95% CI 1.22-1.85), lung cancer (HR=1.73, 95% CI 1.05-2.85), cervical cancer (HR=2.80, 95% CI 2.26-3.47) and colorectal cancer (HR=3.36, 95% CI 2.19-5.15), rather than in breast cancer and HCC. In Caucasian populations, high expression of Bmi-1 was associated with better OS in breast cancer (HR=0.70, 95% CI 0.51-0.97), but it showed no significance in oesophageal carcinoma. In conclusion, high Bmi-1 expression was significantly associated with poor survival in Asian patients with oesophageal carcinoma, gastric cancer, lung cancer, colorectal cancer and cervical carcinoma, whereas high level of Bmi-1 can predict better prognosis in Caucasian patients with breast cancer., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)