Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

Yang, Wen; Lin, Anqi; Zhu, Wei; Wei, Ting; Luo, Peng; Guo, Linlang; Zhang, Jian

doi:10.3389/fphar.2021.645862

Cited by 7 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, users can find that ZFHX3 is associated with significantly longer OS time in the immunotherapy cohort of Samstein-NSCLC (22). The CARD11 gene can also be quickly identified as a gene significantly associated with the prognosis of skin cutaneous melanoma (SKCM) patients receiving immunotherapy (37).…”

Section: Discussionmentioning

confidence: 99%

CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer

Lin

Wei

et al. 2022

Briefings in Bioinformatics

Self Cite

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) have completely changed the approach pertaining to tumor diagnostics and treatment. Similarly, immunotherapy has also provided much needed data about mutation, expression and prognosis, affording an unprecedented opportunity for discovering candidate drug targets and screening for immunotherapy-relevant biomarkers. Although existing web tools enable biologists to analyze the expression, mutation and prognostic data of tumors, they are currently unable to facilitate data mining and mechanism analyses specifically related to immunotherapy. Thus, we effectively developed our own web-based tool, called Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer (CAMOIP), in which we are able to successfully screen various prognostic markers and analyze the mechanisms involved in biomarker expression and function, as well as immunotherapy. The analyses include information relevant to survival analysis, expression analysis, mutational landscape analysis, immune infiltration analysis, immunogenicity analysis and pathway enrichment analysis. This comprehensive analysis of biomarkers for immunotherapy can be carried out by a click of CAMOIP, and the software should greatly encourage the further development of immunotherapy. CAMOIP provides invaluable evidence that bridges the information between the data of cancer genomics based on immunotherapy, providing comprehensive information to users and assisting in making the value of current ICI-treated data available to all users. CAMOIP is available at https://www.camoip.net.

show abstract

Section: Discussionmentioning

confidence: 99%

CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer

Lin

Wei

et al. 2022

Briefings in Bioinformatics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Great advances have been made in treating patients with LUAD, especially with the rapid development of immunotherapy, and patient survival has significantly improved ( Sun et al, 2020 ; Wen et al, 2021 ). However, only a quarter of LUAD patients respond to PD-1/PD-L1 inhibitor monotherapy ( Reck et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis identifies proteasome 26S subunit, ATPase (PSMC) family genes, and related signatures associated with prognosis, immune profile, and therapeutic response in lung adenocarcinoma

et al. 2023

View full text Add to dashboard Cite

Background: Proteasome 26S subunit, ATPase gene (PSMC) family members play a critical role in regulating protein degradation and are essential for tumor development. However, little is known about the integrative function and prognostic significance of the PSMC gene family members in lung cancer.Methods: First, we assessed the expression and prognostic features of six PSMC family members in pan-cancer from The Cancer Genome Atlas (TCGA) dataset. Hence, by focusing on the relationship between PSMC genes and the prognostic, genomic, and tumor microenvironment features in lung adenocarcinoma (LUAD), a PSMC-based prognostic signature was established using consensus clustering and multiple machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO) Cox regression, CoxBoost, and survival random forest analysis in TCGA and GSE72094. We then validated it in three independent cohorts from GEO and estimated the correlation between risk score and clinical features: genomic features (alterations, tumor mutation burden, and copy number variants), immune profiles (immune score, TIDE score, tumor-infiltrated immune cells, and immune checkpoints), sensitivity to chemotherapy (GDSC, GSE42127, and GSE14814), and immunotherapy (IMvigor210, GSE63557, and immunophenoscore). Twenty-one patients with LUAD were included in our local cohort, and tumor samples were submitted for evaluation of risk gene and PD-L1 expression.Results: Nearly all six PSMC genes were overexpressed in pan-cancer tumor tissues; however, in LUAD alone, they were all significantly correlated with overall survival. Notably, they all shared a positive association with increased TMB, TIDE score, expression of immune checkpoints (CD276 and PVR), and more M1 macrophages but decreased B-cell abundance. A PSMC-based prognostic signature was established based on five hub genes derived from the differential expression clusters of PSMC genes, and it was used to dichotomize LUAD patients into high- and low-risk groups according to the median risk score. The area under the curve (AUC) values for predicting survival at 1, 3, and 5 years in the training cohorts were all >.71, and the predictive accuracy was also robust and stable in the GSE72094, GSE31210, and GSE13213 datasets. The risk score was significantly correlated with advanced tumor, lymph node, and neoplasm disease stages as an independent risk factor for LUAD. Furthermore, the risk score shared a similar genomic and immune feature as PSMC genes, and high-risk tumors exhibited significant genomic and chromosomal instability, a higher TIDE score but lower immune score, and a decreased abundance of B and CD8+ T cells. Finally, high-risk patients were suggested to be less sensitive to immunotherapy but had a higher possibility of responding to platinum-based chemotherapy. The LUAD samples from the local cohort supported the difference in the expression levels of these five hub genes between tumor and normal tissues and the correlation between the risk score and PD-L1 expression.Conclusion: Overall, our results provide deep insight into PSMC genes in LUAD, especially the prognostic effect and related immune profile that may predict therapeutic responses.

show abstract

“…In addition to the overall mutation burden, TMB-related specific mutations such as MGA [ 54 ], EPHA5 , [ 55 ], CTNNA2 [ 56 ], and co-mutation of FAT3 and LRP1B [ 57 ] have been found as novel predictive biomarkers for ICIs response in nonsquamous NSCLC or LUSD. Hypermutation of driver genes may have a distinct impact on MSI in tumors [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of Tumor Mutational Burden and DNA Damage Repair Gene Mutations with Stromal/Immune Scores Improved Prognosis Stratification in Patients with Lung Adenocarcinoma

Huang

Mao

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Background. Both the tumor environment and the genomic landscape of lung cancer may shape patient responses to treatments, including immunotherapy, but their joint impacts on lung adenocarcinoma (LUAD) prognosis are underexplored. Methods. RNA sequencing data and whole-exome sequencing results were downloaded from the TCGA database, and only LUAD-related data were included in this study. Based on gene expression data, the ESTIMATE algorithm was used to estimate stromal and immune scores, and CIBERSORT analysis was used for quantification of the relative abundances of immune cells. Somatic mutations were used for calculating tumor mutation burden (TMB). Specific mutations in genes involved in DNA damage repair (DDR) pathways were identified. The individual and joint associations of stromal and immune score, TMB, and DDR gene mutations with 5-year survival were analyzed by the Kaplan–Meier method and multivariate Cox model. Results. LUAD patients with a high (>highest 25%) stromal or immune score had prolonged survival as compared to those with a low (<lowest 25%) score (log-rank P = 0.05 and 0.035, respectively). Patients with both high stromal and immune scores had the most favorable survival. Although the survival differences between patients with high (>highest 25%) and low (<lowest 25%) TMB, or between patients with mutant- and wild-type DDR genes were not statistically significant, a survival benefit from high TMB or DDR gene mutations was observed in patients with high stromal or immune scores. Conclusion. A comprehensive evaluation of transcriptomic signatures and genomic biomarkers may provide a novel avenue for improving prognosis stratification in LUAD.

show abstract

Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

Cited by 7 publications

References 45 publications

CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer

CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer

Pan-cancer analysis identifies proteasome 26S subunit, ATPase (PSMC) family genes, and related signatures associated with prognosis, immune profile, and therapeutic response in lung adenocarcinoma

Combination of Tumor Mutational Burden and DNA Damage Repair Gene Mutations with Stromal/Immune Scores Improved Prognosis Stratification in Patients with Lung Adenocarcinoma

Contact Info

Product

Resources

About