Application of the 'online assessment + FOBT at home' to improve participation and the efficacy of opportunistic screening for colorectal cancer: a retrospective cohort study.

BACKGROUND: Colorectal cancer (CRC) screening faces two major challenges: insufficient screening coverage and poor adherence. A smartphone applet named "Early Screening Assistant (ESA)" was developed to create an online risk-assessment and fecal occult blood test (FOBT) at home. This retrospective study was designed to evaluate whether the new CRC screening strategy can improve the colonoscopy participation rate (PR) and lesion detection rate (DR). METHODS: In total, 6194 individuals who accepted normal health examinations and CRC screening based on the ESA from June 2020 to May 2022 were assigned to the ESA group. Accordingly, 7923 inhabitants who only accepted normal health examinations were assigned to the control group. The colonoscopy PR and neoplastic lesion DR were then compared between the two groups. RESULTS: Overall, a higher proportion of subjects in the ESA group (285 of 6194 [4.6%]) completed colonoscopy than in the control group (126 of 7923, [1.6%]), p < 0.01). The neoplastic lesion DR also significantly increased in the ESA group (76 of 6194 [1.22%]) compared with the control group (15 of 7923 [0.19%]) (p < 0.01). The adjusted diagnostic sensitivity and specificity of the "Online assessment + FOBT at home" were 41.5% and 62.6% for neoplastic lesions, respectively. CONCLUSIONS: This retrospective cohort study confirmed that the new CRC screening strategy based on the "Online assessment + FOBT at home" can improve colonoscopy participation and the neoplastic lesion detection rate and may represent a promising screening strategy for CRC. TRIAL REGISTRATION: This study was registered in China Clinical Trial Registry ( https://www.chictr.org.cn ) on 29/09/2022. REGISTRATION NUMBER: ChiCTR2200064186.

Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene.

In this study, we investigated the functional mechanisms of microRNA-193-3p (miR-193-3p) in human gastric cancer. Quantitative RT-PCR (qRT-PCR) was used to assess whether miR-193-3p was aberrantly expressed in gastric cancer cells and clinical samples from gastric cancer patients. Gastric cancer cell line AGS and MKN-45 cells were stably transduced with lentivirus to downregulate endogenous miR-193-3p. The modulation of miR-193-3p downregulation on gastric cancer proliferation, migration, chemo-drug responses, and tumor explant were assessed by MTT, wound-healing, 5-FU chemoresistance and in vivo tumorigenicity assays, respectively. Downstream target of miR-193-3p, phosphatase and tensin homolog (PTEN) in gastric cancer, was assessed by dual-luciferase reporter assay, qRT-PCR, and western blot. PTEN was knocked down by siRNA in AGS and MKN-45 cells to assess its direct impact on miR-193-3p modulation in gastric cancer. MiR-193-3p was aberrantly upregulated in both gastric cell lines and human gastric tumors. In AGS and MKN-45 cells, miR-193-3p downregulation reduced cancer proliferation, migration and 5-FU chemoresistance in vitro, and tumorigenicity in vivo. PTEN was confirmed to be targeted by miR-193-3p in gastric cancer. PTEN inhibition in AGS and MKN-45 cells directly reversed the anti-tumor modulations of miR-193-3p downregulation on gastric cancer proliferation, migration, and 5-FU chemoresistance. We presented clear evidence showing miR-193-3p played critical role in regulating human gastric cancer through direct targeting on PTEN gene.

Is red blood cell distribution width a prognostic factor for colorectal cancer? A meta-analysis.

Background: RDW might be an easy and cost-effective pre-operative prognostic factor for cancer patients. The aim of the current study was to analyze whether red blood cell distribution width (RDW) was a prognostic factor for colorectal cancer (CRC) patients who underwent radical surgery. Methods: We conducted the searching strategy in three databases including the PubMed, Embase and Cochrane Library from the inception to May 07, 2022, to find eligible studies. In this meta-analysis, we focused on the prognosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). Results: A total of seven studies involving 7,541 patients were included in this meta-analysis. After pooling up the HRs, red blood cell distribution width-coefficient of variation (RDW-CV) was not an independent prognostic factor of OS (HR = 1.48, I 2 = 90%, 95% CI = 0.93 to 2.36, P = 0.10), however, red blood cell distribution width-standard deviation (RDW-SD) was an independent prognostic factor of OS (HR = 1.99, I 2 = 0%, 95% CI = 1.59 to 2.49, P < 0.01). As for DFS, we found that RDW-CV (HR = 1.51, I 2 = 83%, 95% CI = 0.94 to 2.43, P = 0.09 < 0.10) and RDW-SD (HR = 1.77, I 2 = 56%, 95% CI = 0.91 to 3.43, P = 0.09 < 0.10) were both the independent prognostic factors. In terms of CSS, we found that RDW-CV was not an independent prognostic factor (HR = 1.23, I 2 = 95%, 95% CI = 0.72 to 2.10, P = 0.46). Conclusion: RDW-SD was an independent prognostic factor of OS and DFS, and RDW-CV was an independent prognostic factor of DFS.

Does Intraoperative Blood Loss Affect the Short-Term Outcomes and Prognosis of Gastric Cancer Patients After Gastrectomy? A Meta-Analysis.

Purpose: The purpose of the current meta-analysis was to analyze whether intraoperative blood loss (IBL) influenced the complications and prognosis of gastric cancer patients after gastrectomy. Methods: We systematically searched the PubMed, Embase and Cochrane library databases on November 29, 2021. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. This meta-analysis uses RevMan 5.3 for data analysis. Results: A total of nine retrospective studies were included in this meta-analysis, involving 4653 patients. In terms of short-term outcomes, the Larger IBL group has a higher complication rate (OR = 1.94, 95% CI, 1.44 to 2.61, P < 0.0001) and a longer operation time (OR = 77.60, 95% CI, 41.95 to 113.25, P < 0.0001) compared with the smaller IBL group, but the Larger IBL group had higher total retrieved lymph nodes (OR = 3.68, 95% CI, 1.13 to 6.24, P = 0.005). After pooling up all the HRs, the Larger IBL group has worse overall survival (OS) (HR = 1.80, 95% CI, 1.27 to 2.56, P = 0.001) and disease-free survival (DFS) (HR = 1.48, 95% CI, 1.28 to 1.72, P < 0.00001). Conclusion: Larger IBL increased operation time and postoperative complications, and decreased OS and DFS of gastric cancer patients. Therefore, surgeons should be cautious about IBL during operation.

MicroRNA-182 is a potential biomarker for prognosis of gastric cancer: A protocol for meta-analysis and bioinformatics analysis.

BACKGROUND: Being the second leading cause of cancer death in the world, gastric cancer is a common malignant tumor in digestive system. Most patients were diagnosed in advanced stage and had poor prognosis. In recent years, related studies have displayed that MicroRNA-182 (miRNA-182) can promote the proliferation, infiltration, metastasis and drug resistance of tumor cells, so it can be used as a new molecular marker for the early diagnosis, prognosis, and treatment of tumors. However, the expression and prognosis of miRNA-182 in gastric cancer are not clear. Therefore, this study conducted a meta-analysis to further clarify the relationship between the expression of miRNA-182 in gastric cancer and prognosis. In addition, a bioinformatics analysis was adopted to further analyze the possible molecular mechanism of miRNA-182, so as to provide a theoretical basis for the diagnosis, treatment, and prognosis of patients suffering from gastric cancer. METHODS: The following electronic databases were searched on computer: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases. The retrieval time is set to build the database until April 2021. Combined hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the effects of miRNA-182 on the prognosis of gastric cancer. Stata 16.0 software was applied for the meta-analysis. The expression of miRNA-182 in gastric cancer was analyzed by Gene Expression Omnibus database and The Cancer Genome Atlas database. The survival curve of miRNA-182 differential expression was analyzed by OncomiR. The target genes of miRNA-182 were predicted by TargetScan, miRBase, miRTarBase, starBase V2.0, and miRWalk. The target genes were obtained by the intersection of Wayne diagram. DAVID database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis. STRING database and Cytoscape were applied to construct Protein-protein interaction network to obtain key genes (hub gene). The expression of hub gene in gastric cancer was analyzed by gene expression profiling interactive analysis. The survival curve between hub gene and prognosis of gastric cancer was drawn by Kaplan-Meier Plotter database. TIMER database was used to analyze the relationship between hub gene expression and immune cell infiltration in gastric cancer. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study provides high-quality evidence support for the expression of miRNA-182 and the prognosis of gastric cancer. Through bioinformatics analysis, we further discussed the mechanism of miRNA-182 in gastric cancer and the understanding of related pathways. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/EHJ6X.

Long non-coding RNA GAS5 is critical for maintaining stemness and induces chemoresistance in cancer stem-like cells derived from HCT116.

Long non-coding RNAs (lncRNAs) are recognized as critical regulators of self-renewal in human cancer stem-like cells (CSCs), which are a subpopulation of cancer cells primarily responsible for the malignant features of cancer. However, most CSC-related lncRNAs remain unidentified. The results of the present study suggested that growth-arrest-specific transcript 5 (GAS5), a tumor suppressor, exhibited increased expression and was associated with malignant features in human colorectal cancer cell HCT116-derived CSCs. Phenotypic analysis indicated that GAS5 knockdown by specific siRNA significantly decreased CSC self-renewal capacity, proliferation and migration. Moreover, GAS5 knockdown sensitized CSCs to the chemotherapeutic agents 5-fluorouracil and doxorubicin by inducing apoptosis detected by Annexin V-FITC/PI double staining. Inhibition of Nodal growth differentiation factor (NODAL) signaling, which has been reported to be protected by GAS5, presented similar chemosensitivity effects to the GAS5 knockdown results. The present study also assessed the effects of GAS5 overexpression on HCT116 cells, and revealed that overexpression of GAS5 sensitized HCT116 cells to chemotherapeutic agents, which is the opposite of the effect observed in CSCs derived from HCT116 cells. Therefore, it was hypothesized that GAS5 may function as a critical factor for maintaining stemness and that it may exert protective effects on CSCs in a NODAL-dependent manner. Collectively, the results of the present study indicate that GAS5 may be a promising therapeutic target for overcoming malignant features and chemoresistance in colorectal cancer cells.