Objective: To investigate the effect of COVID-19 infection on pancreatic cancer. Methods: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. Results: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. Conclusion: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Background: Since its introduction in 2008, sorafenib has remained the standard first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Nevertheless, its clinical benefits are often compromised by the rapid emergence of drug resistance. This study explores the molecular mechanisms underlying sorafenib resistance, with particular emphasis on the involvement of connective tissue growth factor (CCN2/CTGF) in the regulation of c-Met signaling pathways. Methods: We began by evaluating CCN2 expression levels in HCC tissue samples via immunohistochemistry and analyzing their correlation with clinicopathological characteristics. To functionally characterize CCN2, we established stable HCC cell lines with either knockdown or overexpression of the gene using lentiviral transduction. The effects of CCN2 on cellular proliferation and drug resistance were evaluated using cell counting kit-8 (CCK-8) and colony formation assays. To elucidate the downstream signaling mechanisms, a tyrosine kinase PCR array was employed to identify expression changes within the tyrosine kinase superfamily after CCN2 knockdown. Further investigation into the molecular mechanism by which CCN2 promotes sorafenib resistance was conducted using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence. Finally, the therapeutic potential of co-targeting CCN2 and sorafenib was validated in a nude mouse xenograft tumor model. Results: Our results establish that CCN2 overexpression significantly enhances HCC proliferation, while also inducing resistance to sorafenib. Mechanistically, we identified that CCN2 binds to integrin αV, triggering focal adhesion kinase (FAK) phosphorylation, which in turn promotes yes-associated protein (YAP) nuclear translocation and leads to the transcriptional upregulation of c-Met. This proposed signaling axis was consistently supported by tyrosine kinase PCR array, co-immunoprecipitation, and western blot analyses. Ultimately, in vivo experiments confirmed that simultaneously targeting CCN2 and administering sorafenib produces a synergistic effect, markedly inhibiting tumor growth and restoring therapeutic sensitivity. Conclusion: These results not only elucidate a novel CCN2/FAK/YAP/c-Met axis in sorafenib resistance but also provide a mechanistic rationale for dual-targeting strategies to improve outcomes in advanced HCC.

Background: Mediator complex subunit 10 (MED10) serves as a critical regulator of eukaryotic gene expression by facilitating RNA polymerase II activity. Our investigation aims to characterize MED10’s functional contributions and underlying molecular pathways in hepatocellular carcinoma (HCC) development. Methods: MED10 expression patterns in HCC and their correlation with clinicopathological parameters and patient outcomes were examined using bioinformatics databases and immunohistochemistry. Subsequently, we systematically investigated the biological functions of MED10 in the malignant progression of HCC through comprehensive in vitro experiments, including assessments of cell migration (transwell and wound healing assays), proliferative capacity (cell counting kit-8, colony formation, and 5-Ethynyl-2′-deoxyuridine assays), and cell cycle progression (flow cytometry analysis). Furthermore, we elucidated the underlying molecular mechanisms using real-time quantitative PCR (RT-qPCR), western blotting, immunofluorescence staining, and public database analyses. Furthermore, an in vivo subcutaneous xenograft model was employed to validate MED10’s impact on tumor growth. Results: The results revealed a marked increase in MED10 expression levels within HCC tissues, showing a strong association with unfavorable clinical outcomes. Mechanistically, MED10 induced the epithelial-mesenchymal transition (EMT) and enhanced HCC cell migration. Moreover, MED10 overexpression drives HCC cell cycle progression and proliferation by activating rapidly accelerated fibrosarcoma 1 (RAF1), a process potentially mediated through the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)/cellular myelocytomatosis oncogene (c-Myc) signaling axis. Conclusion: MED10 promotes HCC cell migration and EMT but, more importantly, also drives cell cycle progression and proliferation via RAF1 activation, and is related to the MEK/ERK/c-Myc axis.

Early recurrence remains a major challenge in the management of hepatocellular carcinoma (HCC), yet its molecular mechanisms are not fully understood. In this study, we applied an integrative multi‐omics strategy at single‐cell resolution to explore potential drivers of early HCC recurrence (recurrence time < 2 years) and to develop a predictive framework. By combining single‐cell RNA sequencing, proteomics, transcriptomics, and clinical feature analysis, we identified 14 relapse‐associated proteins, including CD274, B2M, MYC, and CASP3, as candidate risk factors. Transcriptomic profiling suggested the enrichment of pathways such as MYC‐TARGETS‐V2 and INTERFERON‐GAMMA‐RESPONSE. Single‐cell analysis indicated reduced immune cell infiltration in recurrent tumors, with myeloid cells (particularly cDC2 and macrophages) showing B2M‐associated reprogramming characterized by HLA downregulation and altered GAS6/PROS1 signaling, consistent with tumor‐associated macrophage‐like phenotypes. A LASSO regression model based on cDC2 and macrophage signature genes demonstrated moderate predictive performance in both the training and validation cohorts (AUC > 0.65). Drug sensitivity analyses further suggested that vandetanib may have the potential to inhibit recurrence by targeting B2M‐related pathways. These findings provide evidence that B2M may contribute to remodeling of the immune microenvironment in recurrent HCC. Our integrative single‐cell multi‐omics approach highlights a possible mechanism of early recurrence and offers a preliminary predictive tool with therapeutic implications.

Aims: Splenectomy combined with pericardial devascularization is one of the important methods to treat hypersplenism, gastrointestinal bleeding, and other complications caused by liver cirrhosis; however, it is accompanied by a high risk of portal vein thrombosis (PVT). This study aimed to explore the preventive and therapeutic effects of proximal splenic vein ligation (PSVL) with postoperative transcatheter anticoagulant therapy (TCAT) on PVT.Methods: This study retrospectively selected 143 patients with liver cirrhosis and portal hypertension, who received splenectomy combined with pericardial devascularization from June 30, 2018 to June 30, 2021. According to computed tomography photography, within 1 week before the operation, the patients were divided into a prevention group (without preoperative PVT, n = 112) and a treatment group (preoperative PVT, n = 31). Then, each group was subdivided based on the treatment and prevention measures into PSVL + TCAT (n = 70) and systemic anticoagulant therapy (SAT) subgroups (n = 73). The preventive and therapeutic effects of PSVL followed by TCAT on PVT were analyzed.Results: The operation time in the PSVL + TCAT subgroups was longer than that in the SAT subgroups (185 ± 76 min vs. 161 ± 55 min; p < 0.01). There was no difference between the two subgroups in terms of operative bleeding (345 ± 82 mL vs. 336 ± 65 mL; p > 0.50). There was no operative death, and all patients recovered uneventfully. In the prevention group, procedure‐related complications occurred in two patients in the PSVL + TCAT subgroup (3.7% [2/54]), including one patient with slight pancreatitis and one patient with chylous leakage, owing to mobilization of the pancreas. The PVT incidence in the prevention group was significantly different between the two subgroups at postoperative 7th day, 3rd month, and 6th month (PSVL + TCAT: 0%, 11.1%, and 5.6% vs. SAT: 39.7%, 31.0%, and 20.7%, respectively; all p < 0.05). In the treatment group, the thrombus regression rate at postoperative 7th day and disappearance rates at the 3rd month and the 6th month of the PSVL + TCAT subgroup were significantly higher than those in the SAT subgroup after anticoagulant and thrombolysis therapy (PSVL + TCAT: 75.0%, 68.8%, and 87.5% vs. SAT: 20.0%, 26.7%, and 40.0%; all p < 0.05).Conclusions: PSVL + TCAT reduces the risk of PVT after splenectomy and is safe and effective in treating PVT during surgery for portal hypertension.

BACKGROUND Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date. METHODS Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well as the R package to assess Polε family members in HCC for their potential biological functions. RESULTS We found that the four target genes were significantly upregulated in HCC (P < 0.001), their high expression was associated with a lower survival rate (P < 0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups showed higher drug sensitivity in some chemotherapeutic drugs(P < 0.001). CONCLUSIONS The POLE1/2/3 are potential prognostic predictive molecules for HCC and correlate with immune infiltration, and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may be a biological predictor of HCC chemotherapy sensitivity.