Xuezhong Zhang

The RNA exosome complex (EXOSC1-10) orchestrates 3^'-5^' RNA processing and decay, yet its family-wide landscape and clinical relevance in lung adenocarcinoma (LUAD) remain incompletely defined. Here, we conducted an integrative multi-omics analysis of EXOSC family members in LUAD using public transcriptomic and proteomic resources, external validation cohorts, and single-cell data. Across TCGA (59 normal vs. 515 tumors), all EXOSC genes were significantly upregulated in tumors, with concordant increases for most proteins in CPTAC and immunohistochemistry evidence from the Human Protein Atlas. Survival analyses identified EXOSC2, EXOSC3 and EXOSC5 as prognostically informative, with elevated EXOSC2/EXOSC5 also associated with inferior disease-specific survival. Receiver operating characteristic analyses indicated moderate-to-high diagnostic performance for several EXOSC genes, supported by qRT-PCR validation in LUAD cell lines and confirmation in GSE31210. Clinicopathological correlations linked EXOSC1-5 and EXOSC8-10 to advanced stage and metastatic features, whereas EXOSC6 and EXOSC7 showed comparatively limited or context-dependent associations, suggesting functional heterogeneity within the family. Genomic profiling revealed recurrent alterations in 11.83% of patients, with EXOSC4 exhibiting the highest alteration frequency (predominantly amplifications), and network analyses identified core interacting partners centered on RNA surveillance machinery. EXOSC expression was broadly correlated with RNA modification regulators (m¹A/m⁵C/m⁶A) and displayed heterogeneous relationships with immune checkpoint genes and immune infiltration, while higher EXOSC expression consistently associated with lower ESTIMATE-derived microenvironment scores and an immune profile characterized by Th2/T helper enrichment with reduced cytotoxic and antigen-presenting populations. Gene set enrichment analyses implicated cell-cycle regulation, senescence, chromatin-related programs and extracellular matrix pathways, and EXOSC-high tumors were associated with increased tumor mutational burden and homologous recombination deficiency, together with enrichment of DNA damage response pathways. Single-cell analysis (GSE146100) localized highest EXOSC expression to proliferating monocytes/macrophages and suggested TGF-β-linked communication with endothelial and T-cell compartments. Exploratory translational analyses further indicated an association between EXOSC9 and predicted cisplatin sensitivity. Collectively, these findings position the EXOSC family as a clinically and biologically relevant axis in LUAD, linking RNA surveillance dysregulation to immune contexture and genomic instability, and highlight subunit-specific heterogeneity that warrants mechanistic validation.

Background Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with poor prognosis and high relapse rates. While the TNFAIP8 gene family (TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3) is implicated in cancer and immune regulation, its role in AML remains unclear. This study utilized bioinformatics analyses to investigate their expression, prognostic significance, genetic alterations, and immune associations in AML. Methods The expression levels and clinical significance of TNFAIP8 family genes in AML were evaluated using UCSC XENA databases. Kaplan–Meier survival analysis was performed to assess overall survival (OS) differences, and receiver operating characteristic (ROC) curves were utilized to evaluate the prognostic predictive abilities of these genes. Genetic alterations were analyzed using the cBioPortal platform, while immune infiltration was examined through ssGSEA and Spearman correlation analysis. Functional enrichment analysis of co-expressed genes was conducted using the KEGG and GO databases. Results TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were significantly overexpressed in AML tissues compared to normal tissues (P < 0.001). However, Kaplan–Meier survival analysis revealed no significant association between their expression levels and OS in AML patients. ROC curve analysis showed that TNFAIP8L2 had the highest predictive accuracy (AUC = 1.000) among the family members, followed by TNFAIP8L1 (AUC = 0.728), TNFAIP8 (AUC = 0.709), and TNFAIP8L3 (AUC = 0.629). Clinicopathological analysis indicated that TNFAIP8 and TNFAIP8L1 expressions were associated with poor cytogenetic risk, while TNFAIP8L3 expression correlated strongly with elevated bone marrow blasts (P < 0.001). Mutation analysis revealed a low frequency of genetic alterations, with TNFAIP8L1 being the only gene with mutations in 0.53% of cases. Immune infiltration analysis demonstrated that TNFAIP8 and TNFAIP8L3 were positively correlated with myeloid-derived suppressor cells (MDSCs), while TNFAIP8L1 expression was associated with natural killer (NK) cell enrichment. Conclusion TNFAIP8 family genes play distinct roles in AML pathogenesis and immune regulation. TNFAIP8L2 shows promise as a prognostic biomarker, while TNFAIP8 and TNFAIP8L1 may indicate adverse cytogenetic risk. The study highlights their potential as therapeutic targets in AML.

Background TMEM9, a transmembrane protein, has emerged as a significant player in tumor progression, yet its comprehensive role across various cancers remains unclear. This study investigates the expression patterns, genetic alterations, immune associations, and prognostic implications of TMEM9 across multiple cancer types using large-scale bioinformatics approaches. Methods TMEM9 expression was analyzed in normal and tumor tissues using data from the TCGA and GTEx databases, with protein expression verified via CPTAC datasets. The prognostic impact of TMEM9 was assessed using overall survival (OS) and disease-free survival (DFS) analyses across various cancers. Genetic alterations, including mutation types and copy number alterations, were explored using the cBioPortal platform. We also examined DNA methylation, RNA modifications, and immune infiltration correlations using bioinformatics tools, including TIMER2 and UALCAN. TMEM9’s relationship with tumor mutational burden (TMB) and microsatellite instability (MSI) was analyzed, and gene enrichment analyses were performed using the STRING database and GO/KEGG pathway analyses. Results TMEM9 was significantly overexpressed in several cancers, including ACC, BLCA, BRCA, CHOL, COAD, GBM, and others. Elevated TMEM9 expression correlated with worse OS and DFS in ACC, CESC, KICH, UVM, and additional tumor types. Genetic alterations, predominantly amplifications, were frequent in BRCA, LIHC, and UCEC. DNA methylation analysis revealed hypermethylation in tumors like HNSC and KIRC, while RNA modification analyses showed TMEM9 associations with m6A and m1A-related genes. TMEM9 expression was strongly correlated with immune infiltration, particularly cancer-associated fibroblasts in tumors like THYM and HNSC. Positive associations between TMEM9 and TMB/MSI were observed in several cancers, suggesting genomic instability. Enrichment analyses identified TMEM9 involvement in pathways related to the endoplasmic reticulum, Wnt signaling, and protein processing. Conclusion TMEM9 plays a crucial role in cancer progression, influencing gene expression, immune modulation, and genomic instability. These findings highlight TMEM9 as a potential prognostic biomarker and therapeutic target across multiple cancer types.

Background: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3. Methods: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways. Results: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance. Conclusion: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.

TNFAIP8L1, as a recently identified member in TNFAIP8 family, plays an important role in tumorigenesis. However, a pan-cancer analysis of TNFAIP8L1 in human tumors has not been conducted until now. The main purpose of study is to investigate TNFAIP8L1 during 33 different types of human tumors by using TCGA and GTEx. The pan-cancer analysis showed that TNFAIP8L1 was significantly over-expressed in 15 cancers and low-expressed in 9 cancers. There were distinct relations between TNFAIP8L1 expression and prognosis of patients with cancer. Furthermore, we also found that DNA methylation and RNA modification of TNFAIP8L1 were associated with many cancers. And then, we detected that TNFAIP8L1 level was positively associated with cancer-associated fibroblasts (CAFs) in many tumors. And, we obtained that TNFAIP8L1 expression was related with most of immune inhibitory and stimulatory genes in multiple types of tumors. We also found TNFAIP8L1 expression was correlated with most of chemokine, receptor, MHC, immunoinhibitor and immunostimulator gens in most of cancers. Moreover, we detected TNFAIP8L1 expression was associated with TMB and MSI in several tumors. Finally, TNFAIP8L1 gene had a significant positive association with 5 genes including BCL6B, DLL4, PCDH12, COL4A1 and DLL4 in the majority of tumors. GO enrichment and KEGG pathway analyses showed that TNFAIP8L1 in thepathogenesis of cancer may be related to “purine nucleoside binding,” “purine ribonucleoside binding,” “ECM-receptor interaction,” etc. Our first pan-cancer study may provide a deep comprehending of TNFAIP8L1 in tumoeigenesis from different tumors.

The purpose of this study was to explore the cytotoxicity of Gloydius brevicauda venom on tumor cells. Hela and Hep G2 cells were used as the research subjects. The MTT assay was employed to investigate the proliferative activity of snake venom on tumor cells. The cell scratch assay was conducted to study the migration ability of tumor cells treated with snake venom. The Hoechst 33258 fluorescent staining method was utilized to examine the damage caused by snake venom on tumor cells. The results demonstrated that the half maximal inhibitory concentration (IC50) of the venom on Hela and Hep G2 cells at 48 hours was 8.176 µg/ml and 12.276 µg/ml, respectively. Furthermore, at a concentration of 4 µg/ml, the venom was able to inhibit the migration of tumor cells. Cell nuclear fluorescence staining revealed that the venom at concentrations of 8 µg/ml and 12 µg/ml induced DNA condensation in Hela and Hep G2 cells, respectively. In conclusion, the venom of Gloydius brevicauda was found to inhibit cell proliferation and migration, as well as induce cell apoptosis.