Stomach adenocarcinoma (STAD) is a malignant tumor with high histological heterogeneity. However, the potential mechanism of STAD tumorigenesis remains to be elucidated. The purpose of our research was to identify candidate genes associated with the diagnosis, progression, prognosis, and immunotherapeutic targets of STAD. Based on tumor samples from the GSE28541 dataset, weighted gene co‐expression network analysis revealed 16 modules related to STAD stage and grade. The salmon module emerged as the most relevant module (cor = 0.34), and functional enrichment analysis showed that the genes in the salmon were primarily related to major histocompatibility complex, immune response, and cell differentiation. Toll‐like receptor 7 (TLR7) was recognized as the real hub gene in the salmon module. Compared to normal stomach tissues, the transcriptional and translational levels of TLR7 were significantly elevated in STAD. Receiver operating characteristic curves verified that TLR7 displayed remarkable sensitivity and specificity for the diagnosis of STAD. The functions of TLR7 were primarily enriched in the regulation of Toll‐like receptor signaling pathway, pattern recognition receptor signaling pathway, and innate immune response. Overexpression of TLR7 tended to indicate more advanced STAD, higher degree of STAD, and poorer prognosis of STAD. In addition, TLR7 expression was positively correlated with immune cell infiltration and immune checkpoint expression. Somatic copy number alteration of TLR7 was also significantly related to immune cell infiltration. In conclusion, this study revealed the crucial role of TLR7 in STAD and provided new perspectives for the selection of biomarkers, progression and prognosis indicators, and immunotherapeutic targets for STAD.

Introduction: The coronavirus disease 2019 (COVID-19), emerged in late 2019, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk factors for idiopathic pulmonary fibrosis (IPF) and COVID-19 are reported to be common. This study aimed to determine the potential role of differentially expressed genes (DEGs) common in IPF and COVID-19. Materials and methods: Based on GEO database, we obtained DEGs from one SARS-CoV-2 dataset and five IPF datasets. A series of enrichment analysis were performed to identify the function of upregulated and downregulated DEGs, respectively. Two plugins in Cytoscape, Cytohubba and MCODE, were utilized to identify hub genes after a protein-protein interaction (PPI) network. Finally, candidate drugs were predicted to target the upregulated DEGs. Results: A total of 188 DEGs were found between COVID-19 and IPF, out of which 117 were upregulated and 71 were downregulated. The upregulated DEGs were involved in cytokine function, while downregulated DEGs were associated with extracellular matrix disassembly. Twenty-two hub genes were upregulated in COVID-19 and IPF, for which 155 candidate drugs were predicted (adj.P.value < 0.01). Conclusion: Identifying the hub genes aberrantly regulated in both COVID-19 and IPF may enable development of molecules, encoded by those genes, as therapeutic targets for preventing IPF progression and SARS-CoV-2 infections.

Background: The functional significance of ADAMs family members in the immune infiltration of pancreatic adenocarcinoma (PAAD) awaits elucidation. Methods: ADAMs family members with significant expression were identified among differentially expressed genes of PAAD based on The Cancer Genome Atlas (TCGA) database followed by a verification based on the Oncomine database. The correlation of ADAMs in PAAD was estimated with the Spearman’s rho value. The pathway enrichment of ADAMs was performed by STRING and GSEALite, respectively. The protein–protein interaction and Gene Ontology analyses of ADAMs and their similar genes were exanimated in STRING and visualized by Cytoscape. Subsequently, the Box-Whisker plot was used to show a correlation between ADAMs and different tumor grade 1/2/3/4 with Student’s t-test. TIMER was applied to estimate a correlation of ADAMs expressions with immune infiltrates and immune checkpoint blockade (ICB) immunotherapy-related molecules. Furthermore, the effect of copy number variation (CNV) of ADAMs genes was assessed on the immune infiltration levels. Result: ADAM8/9/10/12/15/19/28/TS2/TS12 were over-expressed in PAAD. Most of the nine ADAMs had a significant correlation. ADAM8/12/15/19 expression was remarkably increased in the comparison between grade 1 and grade 2/3 of PAAD. ADAM8/9/10/12/19/28/TS2/TS12 had a positive correlation with almost five immune infiltrates. ADAM12/19/TS2/TS12 dramatically related with ICB immunotherapy-related molecules. CNV of ADAMs genes potentially influenced the immune infiltration levels. Conclusion: Knowledge of the expression level of the ADAMs family could provide a reasonable strategy for improved immunotherapies to PAAD.

Lung cancer is a very aggressive cancer characterized with molecular heterogeneities in different subtypes, including lung adenocarcinoma and lung squamous cell carcinoma. However, few related molecular signatures have been established for the treatment of lung cancer subtypes. Polo‐like kinase (PLK) family is a crucial regulator during cell division. Aberrant genetic and epigenetic alteration of PLK members plays a controversial role among different cancers. In this study, we performed an analysis of transcriptional and protein expression to identify overexpressed PLK1/4 and under‐expressed PLK2/3 in lung cancer subtypes. We then analysed biological function of PLKs and related genes. Besides, we estimated a correlation of PLKs with patient's genders and TP53 mutation in lung cancer. Higher PLK1/4 expression was significantly associated with male patient and TP53 mutant status, separately. Moreover, we carried out a methylation profile analysis including methylation level, DNA methyltransferases correlation and survival analysis of global methylation. Global methylation survival analysis showed that prognostic value of PLK1/2/4 methylation remained the same significant trend between two lung cancer subtypes, whereas prognostic value of PLK3 methylation lacked consistency. Taken together, these results provided instructive insights into a comprehensive evaluation for advanced therapeutic strategy based on epigenetic evidences.

GTPase of immunity-associated proteins (GIMAPs) are frequently prescribed as important components of immune regulation complexes, which were known to play key roles in lung adenocarcinoma. However, little is known about the function of distinct GIMAPs in lung adenocarcinoma. To address this issue, this study investigated the biological function and pathway of GIMAPs in lung adenocarcinoma using multiple public databases. Absent expression of GIMAPs was found in lung adenocarcinoma at mRNA and protein levels. While a purity-corrected value uncovered that all GIMAPs were positively associated with the immune infiltration of lung adenocarcinoma. Furthermore, the expressions of GIMAPs were considered to be negatively associated with clinical cancer stages, patient's gender and pathological tumor grades in patients with lung adenocarcinoma. Besides, higher mRNA expression of GIMAPs was significantly associated with longer overall survival of patients with lung adenocarcinoma. Taken together, these results may enable GIMAPs family members as diagnostic and survival biomarker candidates or even potential therapeutic targets for patients with lung adenocarcinoma.

Intrahepatic cholangiocarcinoma (CHOL) remains a rare malignancy, ranking as the leading lethal primary liver cancer worldwide. However, the biological functions of integrator complex subunit 8 (INTS8) in CHOL remain unknown. Thus, this research aimed to explore the potential role of INTS8 as a novel diagnostic or therapeutic target in CHOL. Differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO) datasets were obtained by the “RRA” package in R software. The “maftools” package was used to visualize the CHOL mutation data from The Cancer Genome Atlas (TCGA) database. The expression of INTS8 was detected by performing quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry in cell lines and human samples. The association between subtypes of tumour-infiltrating immune cells (TIICs) and INTS8 expression in CHOL was determined by using CIBERSORT tools. We evaluated the correlations between INTS8 expression and mismatch repair (MMR) genes and DNA methyltransferases (DNMTs) in pan-cancer analysis. Finally, the pan-cancer prognostic signature of INTS8 was identified by univariate analysis. We obtained the mutation landscapes of an RRA gene set in CHOL. The expression of INTS8 was upregulated in CHOL cell lines and human CHOL samples. Furthermore, INTS8 expression was closely associated with a distinct landscape of TIICs, MMR genes, and DNMTs in CHOL. In addition, the high INTS8 expression group presented significantly poor outcomes, including overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI) (p < 0.05) in pan-cancer. INTS8 contributes to the tumorigenesis and progression of CHOL. Our study highlights the significant role of INTS8 in CHOL and pan-cancers, providing a valuable molecular target for cancer research.