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Background: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD)., Methods: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties., Results: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III., Conclusion: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Lung adenocarcinoma (LUAD) has a high mortality rate and is difficult to diagnose and treat in its early stage. Previous studies have demonstrated that small nucleolar RNAs (snoRNAs) play a critical role in tumor immune infiltration and the development of a variety of solid tumors. However, there have been no studies on the correlation between tumor-infiltrating immune-related snoRNAs (TIISRs) and LUAD. In this study, we filtered six immune-related snoRNAs based on the tissue specificity index (TSI) and expression profile of all snoRNAs between all LUAD cell lines from the Cancer Cell Line Encyclopedia and 21 types of immune cells from the Gene Expression Omnibus database. Further, we performed real-time quantitative polymerase chain reaction (RT-qPCR) to validate the expression status of these snoRNAs on peripheral blood mononuclear cells (PBMCs) and lung cancer cell lines. Next, we developed a TIISR signature based on the expression profiles of snoRNAs from 479 LUAD patients filtered by the random survival forest algorithm. We then analyzed the value of this TIISR signature (TIISR risk score) for assessing tumor immune infiltration, immune checkpoint inhibitor (ICI) treatment response, and the prognosis of LUAD between groups with high and low TIISR risk score . Further , we found that the TIISR risk score groups showed significant differences in biological characteristics and that the risk score could be used to assess the level of tumor immune cell infiltration, thereby predicting prognosis and responsiveness to immunotherapy in LUAD patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β , epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53 , PTEN and RB , and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance., (© 2021 The Author(s).)