RESUMO
BACKGROUND: Biomarkers for colorectal cancer (CRC) can complement population screening methods, but so far, few plasma proteins have been identified as biomarkers for CRC. This study aims to identify potential protein biomarkers and therapeutic targets for CRC within the proteome range. METHODS: We extracted summary-level data of circulating protein from 7 published genome-wide association studies (GWASs) of plasma proteome for Mendelian randomization (MR), summary-data-based MR (SMR), and co-localization analyses to screen and validate proteins with causal effects in CRC. In addition, we further conducted druggability evaluation, prognosis analysis at the transcriptional level, and enrichment expression at the single-cell level, highlighting the important role of these plasma protein biomarkers in CRC. RESULTS: We identified 117 plasma protein biomarkers associated with CRC risk, with 9 proteins showing stronger genetic correlations in Bayesian co-localization (PP.H4 > 0.70). Further, we found 26 protein-coding genes already used in targeted drug development and may potentially become therapeutic targets for CRC. In prognosis analysis, the encoding genes of plasma proteins exhibited consistent effects with MR analysis and can serve as prognostic biomarkers for CRC. Additionally, we also found that the differentially expressed proteins are mainly expressed in fibroblasts, endothelial cells, macrophages, and T cells. CONCLUSION: Our study has identified plasma protein biomarkers associated with CRC risk, which may complement population screening methods for CRC and achieve more precise treatment for patients.
RESUMO
With the increasing application of magnetic compression anastomosis (MCA) in gastrointestinal anastomosis, we identified an interesting phenomenon that an anastomosis is more prone to stenosis after endoscopic gastrointestinal MCA. We hypothesized that the increase in tissue tension during endoscopic procedures is the cause of anastomotic stenosis. In this study, we investigated the effect of tissue tension on gastroduodenal bypass MCA in Sprague-Dawley (SD) rats. Twenty SD rats were divided into the study group (high-tension group, n = 10) and control group (no tension group, n = 10), wherein the rats underwent complete gastroduodenal bypass magnetic anastomosis under high tension and no tension of the digestive tract, respectively. Anastomotic specimens were obtained 4 weeks after the operation, and anastomotic diameters of the two groups were observed and measured. The histological difference was observed by hematoxylin & eosin and Masson staining. The operation was successfully completed in all rats, and all survived until 4 weeks postoperatively. Anastomotic measurements revealed that the anastomosis diameter was significantly smaller in the study group than in the control group, and there were three cases of severe anastomotic stenosis. Histological observation showed that the amount of collagen fibers in the anastomosis was greater in the study group than in the control group. The results suggest that the high-tension state of the digestive tract is an important factor leading to anastomotic stenosis, and thus, we put forward the Yan-Zhang's Tissue Tension Theory of MCA to explain this phenomenon.