Integrated analysis of gene expression and DNA methylation datasets identified key genes and a 6-gene prognostic signature for primary lung adenocarcinoma

Meng, Jing; Cao, Lei; Song, Huifang; Chen, Lichun; Qu, Zhiguo

doi:10.1590/1678-4685-gmb-2020-0465

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…Recently, studies have shown that abnormal expression of GNPNAT1 is related to the carcinogenesis of lung cancer. Wang et al showed that the mRNA and protein expression levels of GNPNAT1 in lung cancer tissues were upregulated compared with normal tissues (22,23). The expression level of GNPNAT1 is related to the clinical stage and prognosis of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma

Sun

et al. 2022

Front. Oncol.

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BackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly important in this process. However, the PRs-related signature that can predict the potential prognostic and immunotherapeutic value in patients with LUAD has not been discovered.MethodsIn this study, we mainly analyzed the effect of phagocytosis regulators on the prognosis of LUAD, and based on multiple screening analyses including differential analysis, univariate Cox analysis, and Lasso analysis, we constructed a prognostic risk model consisting of five genes. To verify the stability of the model, survival analysis and ROC curve verification were carried out through multiple data sets. In addition, we also combined many factors, such as immune infiltrating cells, clinical grouping characteristics, immune examination sites, pro-inflammatory factors, and other factors as well as in vitro cell experiments and clinical tissue samples for further validation analysis.ResultsAfter identifying 29 differentially expressed PRs in LUAD samples, we further constructed a prognostic model consisting of five prognostic signatures (FURIN, KIF23, SASH3, GNPNAT1, and ITGAL). Further survival analysis tests, ROC verification, as well as univariate and multivariate Cox regression analysis showed that the risk score of the model could well predict the prognosis of LUAD patients and could be used as an independent prognostic factor. In addition, we further found that these phagocytic regulators-related signatures were closely related to the immune microenvironment and immunotherapy in LUAD patients, and could well predict the efficacy of immunotherapy in patients. In vitro cell experiments and Immunohistochemistry of clinical tissues showed that the expressions of FURIN, KIF23, SASH3, GNPNAT1 and ITGAL in normal lung cells/tissues and LUAD cells/tissues were consistent with bioinformatics results, and 3 of them had significant differences.ConclusionOur study identified a novel PRs-related signature that has potential application value in predicting the prognosis of LUAD patients and predicting the efficacy of immunotherapy. This provides a new basis for the prognosis assessment of LUAD patients and provides a novel target for immunotherapy of LUAD patients.

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Section: Discussionmentioning

confidence: 99%

“…Wang et al. showed that the mRNA and protein expression levels of GNPNAT1 in lung cancer tissues were upregulated compared with normal tissues ( 22 , 23 ). The expression level of GNPNAT1 is related to the clinical stage and prognosis of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma

Sun

et al. 2022

Front. Oncol.

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“…In primary lung adenocarcinoma and pancreatic cancer, VSIG2 was characterized as a member of the DNA methylation-related prognostic signature ( 60 , 61 ). High expression and methylation of VSIG2 correlated with poor survival in these cancer patients ( 58 , 60 , 61 ).…”

Section: Vsig2mentioning

confidence: 99%

“…VSIG2 expression has been found to be significantly upregulated in patients with nonmuscle invasive bladder cancer but downregulated in patients with muscle invasive bladder cancer; thus, it could serve as a biomarker of invasiveness in bladder cancers ( 59 ). In primary lung adenocarcinoma and pancreatic cancer, VSIG2 was characterized as a member of the DNA methylation-related prognostic signature ( 60 , 61 ). High expression and methylation of VSIG2 correlated with poor survival in these cancer patients ( 58 , 60 , 61 ).…”

Section: Vsig2mentioning

confidence: 99%

V-Set and immunoglobulin domain containing (VSIG) proteins as emerging immune checkpoint targets for cancer immunotherapy

et al. 2022

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The development of immune checkpoint inhibitors is becoming a promising approach to fight cancers. Antibodies targeting immune checkpoint proteins such as CTLA-4 and PD-1 can reinvigorate endogenous antitumor T-cell responses and bring durable advantages to several malignancies. However, only a small subset of patients benefit from these checkpoint inhibitors. Identification of new immune checkpoints with the aim of combination blockade of multiple immune inhibitory pathways is becoming necessary to improve efficiency. Recently, several B7 family-related proteins, TIGIT, VSIG4, and VSIG3, which belong to the VSIG family, have attracted substantial attention as coinhibitory receptors during T-cell activation. By interacting with their corresponding ligands, these VSIG proteins inhibit T-cell responses and maintain an immune suppressive microenvironment in tumors. These results indicated that VSIG family members are becoming putative immune checkpoints in cancer immunotherapy. In this review, we summarized the function of each VSIG protein in regulating immune responses and in tumor progression, thus providing an overview of our current understanding of VSIG family members.

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“…Due to the rise of bioinformatics technology in recent years, numerous studies have emerged to explore the prognostic markers of LUAD from different perspectives. There are relevant tumor marker studies involving the tumor microenvironment 2 , tumor metabolism 3 , cell cycle 4 , DNA methylation 5 , etc., but few studies have been related to hypoxia. This study was conducted to investigate the signature associated with the prognosis of lung adenocarcinoma using hypoxia-related genes as a breakthrough.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-associated prognostic markers and competing endogenous RNA coexpression networks in lung adenocarcinoma

Xiong

Wang

et al. 2022

Sci Rep

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Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC). Hypoxia has been found in 50–60% of locally advanced solid tumors and is associated with poor prognosis in various tumors, including NSCLC. This study focused on hypoxia-associated molecular hallmarks in LUAD. Fifteen hypoxia-related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on data from The Cancer Genome Atlas (TCGA). Then, we investigated the immune status under different hypoxia statuses. Subsequently, we constructed prognostic models based on hypoxia-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNA (ceRNA) theory. Two clusters (Cluster 1 and Cluster 2) were identified with different hypoxia statuses. Cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4+ T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB scores were higher in Cluster 1, indicating an immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated with prognosis under different hypoxia clusters and their related mRNAs and lncRNAs were identified, and a ceRNA network was built. This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of the gene signature and ceRNA theory.

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Integrated analysis of gene expression and DNA methylation datasets identified key genes and a 6-gene prognostic signature for primary lung adenocarcinoma

Cited by 6 publications

References 45 publications

Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma

Identification and validation of a novel phagocytosis regulators-related signature with potential prognostic and immunotherapeutic value in patients with lung adenocarcinoma

V-Set and immunoglobulin domain containing (VSIG) proteins as emerging immune checkpoint targets for cancer immunotherapy

Hypoxia-associated prognostic markers and competing endogenous RNA coexpression networks in lung adenocarcinoma

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