RESUMO
AIM: Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis in hepatocellular carcinoma (HCC). However, the specific protein expression profiles that differentiate HCC with MVI from those without MVI remain unclear. METHODS: The profiles of proteins in early-stage HCC tissues and normal liver tissues were characterized by quantitative proteomics techniques. Immunohistochemical (IHC) staining was undertaken on tissue microarrays from 80 HCC patients to assess the expression of MSH2 and MSH6. Cell counting, colony formation, migration, and invasion assays were carried out in vitro. RESULTS: We identified 5164 proteins in both HCC tissues and adjacent normal liver tissues. Compared to HCC without MVI, 148 upregulated proteins and 97 downregulated proteins were found in HCC with MVI. Particularly noteworthy was the remarkable upregulation of MSH6/MSH2 among these dysregulated proteins in HCC with MVI. Further validation through bioinformatics prediction and IHC confirmed the elevated expression of MSH6/MSH2, which correlated with aggressive disease characteristics and poor prognosis. Receiver operating characteristic curve analyses revealed a substantial area under the curve of 0.761 (specificity 71.79%, sensitivity 73.17%) for the combined use of MSH6/MSH2. Knockdown of MSH6/MSH2 significantly inhibited HCC cell proliferation and invasion in vitro. CONCLUSIONS: Our study establishes MSH6 or MSH2 as an oncogene that is prominently overexpressed during HCC progression, which provides new targets for HCC with MVI.
RESUMO
BACKGROUND: To compare the clinical outcomes and prognosis of total pancreatectomy (TP) and pancreaticoduodenectomy (PD) for the treatment of pancreatic ductal adenocarcinoma (PDAC), and to explore the safety and indications of TP. METHODS: A systematic search was conducted on PubMed, Web of Science, and Embase databases from January 1943 to March 2023 for literatures comparing TP and PD in the treatment of PDAC. The primary outcome was postoperative overall survival (OS), and secondary outcomes included surgery time, blood loss, readmission, hospital stay, perioperative mortality, and overall morbidity. Fixed-effect or random-effect models were selected based on heterogeneity, and odds ratio (OR), mean difference (MD), or hazard ratio (HR) with 95% confidence intervals (CI) were calculated. RESULTS: A total of six studies involving 8396 patients were included in the meta-analysis. There was no statistically significant difference in OS after surgery between the two groups (HR = 1.08, 95% CI: 0.91-1.27; P = 0.38). The TP group had a longer surgery time (MD = 13.66, 95% CI: 4.57-22.75; P = 0.003) and more blood loss (MD = 133.17, 95% CI: 8.00-258.33; P = 0.04) than the PD group. There were no significant differences between the two groups in terms of hospital stay (MD = 0.09, 95% CI: -2.04 to 2.22; P = 0.93), readmission rate (OR = 1.39; 95% CI: 1.00-1.92; P = 0.05), perioperative mortality (OR = 1.29, 95% CI: 0.98-1.69; P = 0.07), and overall morbidity (OR = 0.80, 95% CI: 0.50-1.26; P = 0.33). CONCLUSION: The surgical process of TP is relatively complex, but there is no difference in short-term clinical outcomes and OS compared to PD, making it a safe and reliable procedure. Indications and treatment outcomes for planned TP and salvage TP may differ, and more research is needed in the future for further classification and verification.
