Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It’s necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student’s t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and remains a major therapeutic challenge. In recent years, immune checkpoint inhibitors (ICIs), represented by PD-1/PD-L1 and CTLA-4 inhibitors, have revolutionized the field of HCC treatment and become the cornerstone of standard immunotherapy regimens, drastically altering the treatment landscape for advanced and unresectable HCC. However, primary and/or acquired drug resistance remains the leading cause of treatment failure, severely limiting the long-term clinical benefits of immunotherapy for HCC patients. This review aims to systematically summarize current research on immunotherapy for HCC, with a focus on drug resistance mechanisms across multiple dimensions: immunosuppressive tumor microenvironment, intrinsic tumor cell factors, and systemic and environmental influences. Potential strategies to overcome resistance are discussed, such as rational combination therapy with antiangiogenic or targeted agents, novel immune targets, nanotechnology-enabled precise delivery, and tumor organoid models for personalized treatment. Future advancements should focus on precision multimodal combinations, innovative therapeutic platforms, and individualized strategies guided by multi-omics and AI, aiming to overcome efficacy bottlenecks and improve patient survival.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer death worldwide. Treatment of HCC has shifted from traditional modalities to immunotherapy-centered combination strategies. While the current immunotherapies can substantially reduce the risk of death for patients with HCC, overall survival improvement is limited because of tumor heterogeneity and an immunosuppressive microenvironment. Moreover, the widespread application of these treatments is challenged by high costs, drug resistance, and frequent adverse events. This review outlines the mechanisms of the available HCC immunotherapeutics and summarizes the preclinical explorations of these treatments. We also describe the current clinical applications and underlying mechanisms and discuss issues of resistance and heterogeneity. We further provide an overview of emerging approaches against cancer platforms in HCC, aiming to provide practical references for clinical immunotherapy of HCC.