Lung adenocarcinoma (LUAD) is a common diagnosed disease with high‐mortality rate, and its prognostic implications are under discovered. DNA methylation aberrations are not only an important event for dysregulation of gene expression during tumorigenesis but also a revolution in epigenetics by identifying key prognostic biomarkers for multiple cancers. In this study, we analyzed methylation status of 485 578 CpG sites and RNA‐seq transcriptomes of 20 532 genes for 1095 LUAD samples in TCGA database. The association between DNA methylation and the prognostic value of the corresponding gene expression was identified as well. In total, ten aberrantly methylated and dysregulated genes (AURKA, BLK, CNTN2, HMGA1, PTTG1, TNS4, DAPK2, MFSD2A, THSD1, and WNT7A) were highlighted which were significantly correlated with overall survival of 492 LUAD patients, which were all reported as tumor‐associated genes in other various cancers and worthy of further investigated and might be used as therapeutic targets for LUAD. Together, methylation aberrances regulate gene expression level during tumorigenesis and influence prognosis of LUAD patients. Integrating knowledge of epigenetics and expression of genes can be useful for an in‐depth understanding of cancer mechanism and for the eventual purpose of precisely prognostic and therapeutic target verification.

Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.

The recruitment of neutrophil to the primary cancer has been shown to be steered by neoplastic cells or tumor-educated mesenchymal stromal cells and has a prometastatic effect. However, the neutrophil chemotaxis and their interaction with tumor cells in the distal metastasized tissues remain elusive. In this review, we discussed emerging research on the interaction between neutrophil recruitment and tumor metastasis, which is essential for studying tumor cell invasion and related immunotherapy.

Background: Immune evasion is a crucial event in the progression of pancreatic ductal adenocarcinoma (PDAC). The identification of new immunotherapeutic targets may provide a promising platform for advancing PDAC treatment. This study aims to investigate the role of beta-1,4-galactosyltransferase-5 (B4GALT5) in immune evasion by pancreatic cancer cells and evaluate its potential as an immunotherapeutic target. Methods: We conducted a comprehensive analysis using RNA sequencing data and tissue microarrays from patients with PDAC to investigate the association between B4GALT5 expression and patient prognosis. Using animal models, we further explored the impact of B4GALT5 on the quantity and activity of tumor-infiltrating CD8⁺ T cells. RNA sequencing and co-immunoprecipitation were used to explore the mechanism by which B4GALT5 regulates major histocompatibility complex (MHC-I) levels. Results: Our study demonstrates that high expression of B4GALT5 in tumor cells is significantly associated with poor prognosis in patients with PDAC and reduced cytotoxic activity of tumor-infiltrating CD8⁺ T cells. Specifically, B4GALT5 suppresses MHC-I expression in tumor cells through the endoplasmic reticulum-associated degradation pathway, enabling them to evade immune surveillance by CD8⁺ T cells. Conclusions: B4GALT5 impairs CD8⁺ T-cell recognition of tumor cells by regulating MHC-I levels, thereby promoting immune evasion. This makes B4GALT5 a highly promising immunotherapeutic target for improving the poor prognosis of patients with PDAC.