Search

Background: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. CircRNAs are promising novel biomarkers for CRC. T regulatory (Treg) cells express the immune checkpoint receptor of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and promote tumor immunological tolerance. We therefore investigate the biological functions and mechanisms of circQSOX1 in CRC tumorigenesis; involvement of circQSOX1 in promoting Treg cell-mediated CRC immune escape in anti-CTLA-4 therapy., Methods: Bioinformatics analyses were performed for circQSOX1expressions, specific binding sites, and N6-methyladenosine (m 6 A) motifs of circQSOX1, thatwere further validated with a series of experiments. Functions of circQSOX1 in promoting CRC development, Treg cells-based immune escape, and anti-CTLA-4 therapy response were investigated both in vitro and in vivo., Results: High circQSOX1 expression was associated with carcinogenesis and poor clinical outcome of CRC patients. METTL3-mediated RNA m 6 A modification on circQSOX1 could be read by IGF2BP2 in CRC cells. CircQSOX1 promoted CRC development by regulating miR-326/miR-330-5p/PGAM1 axis. CircQSOX1 regulated glycolysis and promoted immune escape of CRC cells, and inhibits anti-CTLA-4 therapy response in CRC patients., Conclusion: m 6 A-modified circQSOX1 facilitated CRC tumorigenesis by sponging miR-326 and miR-330-5p to promotes PGAM1 expression, which further promoted CRC immune escape by activating glycolysis and inactivating the anti-CTLA-4 therapy response of CRC. Combined treatment with sh-circQSOX1 and anti-CTLA-4 could be a strategy to overcome Treg cell-mediated CRC immune therapy resistance., Competing Interests: Conflicts of interests Each author declared no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients' compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC., Results: In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2-93.7%) and the sensitivity was 88.6% (82.4-93.2%). In terms of different stages, the sensitivities were 79.4% (62.1-91.2%) in patients with stage I, 88.9% (77.3-95.8%) in patients with stage II, 91.4% (76.9-98.2%) in patients with stage III and 96.2% (80.3-99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1-97.0%) and sensitivity of 83.6% (72.5-91.6%). Sensitivities for stage I-III were 87.0% (79.7-92.4%) in the training set and 82.5% (70.2-91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2-11.2%) in healthy control, 30.8% (19.9-43.5%) in benign colorectal disease and 58.3% (27.5-84.7%) in advanced adenoma, while the sensitivities of stage I-IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8-91.2%] versus 41.2% [34.6-48.1%], P < 0.001) under comparable specificity (90.1% [85.4-93.7%] versus 90.6% [86.0-94.1%])., Conclusions: Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.

To comprehensively summarize the association between dietary intake of vitamins A, C, and E and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer, relevant studies were identified in MEDLINE and EMBASE up to 31 October 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I statistics. A total of 13 studies with 3832 CRA cases were included in this meta-analysis. On the basis of the highest versus lowest analysis, dietary intake of vitamin C reduced the risk of CRA by 22% (SRRs 0.78, 95% CIs: 0.62-0.98). Subgroup analyses showed that this relation was not modified by BMI, smoking status, and dietary energy intake. Further, dietary intake of β-carotene was also inversely associated with the risk of CRA. However, dietary intake of vitamins A and E was not associated with the risk of CRA in overall and subgroup analyses (vitamin A: SRRs 0.87, 95% CIs: 0.67-1.14; vitamin E: SRRs 0.87, 95% CIs: 0.69-1.10). Our results indicate that dietary intake of vitamin C and β-carotene, but not vitamins A and E, could reduce the risk of CRA. However, these associations seem to be limited. Further investigation using large samples and a rigorous methodology is warranted.

Inconsistent results regarding the association between red and processed meat intake and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer (CRC), have been reported. To provide a quantitative assessment of this association, we summarized the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until December 31, 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using the Cochran's Q and I(2) statistics. A total of 21 studies (16 case-control studies and five cohort/nested case-control studies) were included in this meta-analysis. The SRRs of CRA were 1.36 (95% CI = 1.17-1.58) for every 100 g/day increase in red meat intake, and 1.24 (95% CI = 1.12-1.36) for the highest versus the lowest level of red meat intake. Nonlinear dose-response meta-analysis indicated that CRA risk increased approximately linearly with increasing intake of red meat up to ~ 90 g/day, where the curve reached its plateau. Subgrouped analyses revealed that the increased risk of CRA with intake of red meat was independent of geographic locations, design and confounders. The SRRs of CRA was 1.28 (95% CI = 1.03-1.60) for per 50 g/day increase in processed meat intake, and 1.17 (95% CI = 1.08-1.26) for the highest versus the lowest level of processed meat intake. Increased intake of red and processed meat is associated with significantly increased risk of CRA., (Copyright © 2012 UICC.)