APOBEC mutational signature predicts prognosis and immunotherapy response in nonsmoking patients with lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer (NSCLC) with poor survival in advanced stage. Nowadays the rate of nonsmoking patients has dramatically increased and may be associated with the presence of driver mutations. Better understanding of the mutation profile data of nonsmoking LUAD patients are critical to predict survival and provide greater benefits to more patients. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) has been shown to play an important role in molecular tumorigenesis of NSCLC. However, the clinical relevance of APOBEC in nonsmoking LUAD remains to be understood. Methods: LUAD patients with somatic mutation and RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) were assessed and screened in the Gene Expression Omnibus. Transcriptome data and mutational signatures were analyzed using R package. Then, we used the least absolute shrinkage and selection operator (LASSO) regression model to construct the APOBEC3 score (APOBEC3 score) model. The prognostic value was evaluated using Kaplan-Meier analysis. Finally, the functional enrichment analysis of differential expressed genes (DEGs) and the immune-related features were also estimated using R package. Results: By analyzing the mutational profile data of NSCLC in the TCGA database, we found that different mutation patterns existed between smoking and nonsmoking patients, and the APOBEC3 family played an important role in the mutation pattern of nonsmoking patients with LUAD. We established an APOBEC3 score and found that TCW (W = A or T) mutation counts were significantly greater in the high APOBEC3 score group than in the low APOBEC3 score group. Furthermore, there were different immune feathers and prognostic values between the high and low APOBEC3 score patients, suggesting an independent prognostic factor of APOBEC3 in nonsmoking LUAD patients. Conclusions: We established a comprehensive view of APOBEC3 mutations in nonsmoking LUAD patients. Our review provides new insights into using the APOBEC3 mutation to predict prognosis and improve the immunotherapy response for future applications.

Identification and validation of hub genes in CD5-positive diffuse large B-cell lymphoma.

CD5+ diffuse large B-cell lymphoma (DLBCL), as a significant heterogeneity category of DLBCL, is reflected in both the molecular biological and genetic levels, which in turn induces ever-changing clinical manifestations, and what mediates tumor survival mechanisms are still unclear. This study aimed to predict the potential hub genes in CD5+ DLBCL. A total of 622 patients with DLBCL diagnosed between 2005 and 2019 were included. High expression of CD5 was correlated with IPI, LDH, and Ann Arbor stage, patients with CD5-DLBCL have longer overall survival. We identified 976 DEGs between CD5-negative and positive DLBCL patients in the GEO database and performed GO and KEGG enrichment analysis. After intersecting the genes obtained through the Cytohubba and MCODE, further external verification was performed in the TCGA database. Three hub genes were screened: VSTM2B, GRIA3, and CCND2, of which CCND2 were mainly involved in cell cycle regulation and JAK-STAT signaling pathways. Analysis of clinical samples showed that the expression of CCND2 was found to be correlated with CD5 (p = 0.001), and patients with overexpression of CCND2 in CD5+ DLBCL had poor prognosis (p = 0.0455). Cox risk regression analysis showed that, for DLBCL, CD5, and CCND2 double positive was an independent poor prognostic factor (HR: 2.545; 95% CI: 1.072-6.043; p = 0.034). These findings demonstrate that CD5 and CCND2 double-positive tumors should be stratified into specific subgroups of DLBCL with poor prognosis. CD5 may regulate CCND2 through JAK-STAT signaling pathways, mediating tumor survival. This study provides independent adverse prognostic factors for risk assessment and treatment strategies for newly diagnosed DLBCL.

Family I84 protease inhibitors likely constitute a Mollusca-specific protein family functioning in host defense.

Protease inhibitors are proteins or small polypeptides functioning in numerous biological processes in all organisms. The I84 family of protease inhibitors in the MEROPS database represents a novel protease inhibitor family that has been reported in 2 bivalves, Crassostrea virginica and Sinonovacula constricta, and is believed to play a role in host defense. In the present study, 7 new members of Family I84 were identified in 2 bivalves, Meretrix meretrix and Mytilus galloprovincialis, and 1 gastropod, Haliotis discus hannai, at the mRNA level via cDNA cloning. The expression patterns of the newly identified genes varied in response to salinity stresses and pathogen-associated molecular pattern stimulations, suggesting their involvement in the host defense of related species. Additionally, analyses of sequence data in public databases did not reveal any Family I84 protease inhibitor molecules in non-molluscan animals. The results indicated that Family I84 protease inhibitors are likely mollusk specific, constituting a unique host defense mechanism in molluscan species.