High <scp>GNG4</scp> expression is associated with poor prognosis in patients with lung adenocarcinoma

Zhou, Bodong; Zhu, Wenbo; Yuan, Shuai; Wang, Yifei; Zhang, Qing; Zheng, Hong; Zhu, Lihong; Xu, Jie

doi:10.1111/1759-7714.14265

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…GNG4 expression was positively correlated with TNM stages, suggesting that GNG4 may be involved in tumour metastasis and progression. The high expression of GNG4 predicted shorter survival in COAD and LUAD, which was consistent with previous studies 16,17,27 . A pan‐cancer immunological correlation of GNG4 aimed to determine cancer types that may benefit from anti‐GNG4 immunotherapy.…”

Section: Discussionsupporting

confidence: 87%

“…Notably, hypermethylated GNG4 was found in bladder cancer and glioblastoma 14,15 . Furthermore, high expression of GNG4 has also been associated with the progression of CRC 16 and a variety of malignant phenotypes of lung adenocarcinoma 17 . GNG4 was demonstrated to be the key element of the CRC TMB, which is essential for immune checkpoint inhibitor (ICI) therapy of CRC 18 .…”

Section: Introductionmentioning

confidence: 99%

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GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

Wang

Zhou

et al. 2023

J Cellular Molecular Medi

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The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan‐cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan‐cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour‐infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

Wang

Zhou

et al. 2023

J Cellular Molecular Medi

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“…GNG4 is a member of the G-protein family and, similar to PIK3C2G, has been closely associated with PI3K/Akt signaling pathway in HNSCC [ 53 ]. Although GNG4 has been reported to be hypermethylated and down-regulated in bladder cancer [ 54 ], breast cancer [ 55 ], and glioblastoma [ 56 ], other studies have shown that GNG4 expression was significantly up-regulated in lung carcinoma [ 57 ], and colorectal cancer [ 58 ]. More interestingly, in a paper by You et al, GNG4 has been listed as one of the up-regulated genes potentially involved in radioresistance in HNSCC [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer

et al. 2022

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Background and purpose Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome. Here, we evaluated the prognostic value of LINE-1 methylation level in OPSCC patients and further addressed the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation. Results In this study, DNA was extracted from 163 formalin-fixed paraffin-embedded tissue samples retrospectively collected from stage III-IVB OPSCC patients managed with curative intent with up-front treatment. Quantitative methylation-specific PCR revealed that LINE-1 hypomethylation was directly associated with poor prognosis (5-year overall survival—OS: 28.1% for LINE-1 methylation < 35% vs. 69.1% for ≥ 55%; p < 0.0001). When LINE-1 methylation was dichotomized as < 55% versus ≥ 55%, interaction with HPV16 emerged: compared with hypermethylated HPV16-positive patients, subjects with hypomethylated HPV16-negative OPSCC reported an adjusted higher risk of death (HR 4.83, 95% CI 2.24–10.38) and progression (HR 4.54, 95% CI 2.18–9.48). Tumor protein p53 (TP53) gene is often mutated and overexpressed in HPV-negative OPSCC. Since p53 has been reported to repress LINE-1 promoter, we then analyzed the association between p53 protein expression and LINE-1 methylation levels. Following p53 immunohistochemistry, results indicated that among HPV16-negative patients with p53 ≥ 50%, LINE-1 methylation levels declined and remained stable at approximately 43%; any HPV16-positive patient reported p53 ≥ 50%. Finally, DNA methylation analysis demonstrated that genome-wide average methylation level at cytosine–phosphate–guanine sites was significantly lower in HPV16-negative OPSCC patients who relapsed within two years. The subsequent integrative analysis of gene expression and DNA methylation identified 20 up-regulated/hypomethylated genes in relapsed patients, and most of them contained LINE-1 elements in their promoter sequences. Conclusions Evaluation of the methylation level of LINE-1 may help in identifying the subset of OPSCC patients with bad prognosis regardless of their HPV status. Aberrant LINE-1 hypomethylation might occur along with TP53 mutations and lead to altered gene expression in OPSCC.

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“…GNG4 was also explored as a downstream target of PSMC2 in gallbladder cancer (GBC) ( Zhu et al, 2021 ). In addition, GNG4 promotes the progression of lung cancer ( Zhou et al, 2022 ). However, rarely studies of GNG4 were discovered in HCC.…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of DNA methylation-driven signatures for prognostic and immune microenvironments evaluation in hepatocellular carcinoma

Shen

Wen

et al. 2022

Front. Genet.

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Liver cancer is the main reason of cancer deaths globally, with an unfavorable prognosis. DNA methylation is one of the epigenetic modifications and maintains the right adjustment of gene expression and steady gene silencing. We aim to explore the novel signatures for prognosis by using DNA methylation-driven genes. To acquire the DNA methylation-driven genes, we perform the difference analysis from the gene expression data and DNA methylation data in TCGA or GEO databases. And we obtain the 31 DNA methylation-driven genes. Subsequently, consensus clustering analysis was utilized to identify the molecular subtypes based on the 31 DNA methylation-driven genes. So, two molecular subtypes were identified to perform those analyses: Survival, immune cell infiltration, and tumor mutation. Results showed that two subtypes were clustered with distinct prognoses, tumor-infiltrating immune cell and tumor mutation burden. Furthermore, the 31 DNA methylation-driven genes were applied to perform the survival analysis to select the 14 survival-related genes. Immediately, a five methylation-driven genes risk model was built, and the patients were divided into high and low-risk groups. The model was established with TCGA as the training cohort and GSE14520 as the validation cohort. According to the risk model, we perform the systematical analysis, including survival, clinical feature, immune cell infiltration, somatic mutation status, underlying mechanisms, and drug sensitivity. Results showed that the high and low groups possessed statistical significance. In addition, the ROC curve was utilized to measure the accuracy of the risk model. AUCs at 1-year, 3-years, and 5-years were respectively 0.770, 0.698, 0.676 in training cohort and 0.717, 0.649, 0.621 in validation cohort. Nomogram was used to provide a better prediction for patients’ survival. Risk score increase the accuracy of survival prediction in HCC patients. In conclusion, this study developed a novel risk model of five methylation-driven genes based on the comprehensive bioinformatics analysis, which accurately predicts the survival of HCC patients and reflects the immune and mutation features of HCC. This study provides novel insights for immunotherapy of HCC patients and promotes medical progress.

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High GNG4 expression is associated with poor prognosis in patients with lung adenocarcinoma

Cited by 14 publications

References 28 publications

GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer

Identification and analysis of DNA methylation-driven signatures for prognostic and immune microenvironments evaluation in hepatocellular carcinoma

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