Loss of G-protein-signaling modulator 2 accelerates proliferation of lung adenocarcinoma via EGFR signaling pathway

Deng, Mingming; Liu, Bofang; Zhang, Zhe; Chen, Yang; Wang, Yizhe; Wang, Ximing; Lv, Qing; Yang, Xianghong; Hou, Kezuo; Che, Xiaofang; Qu, Xiujuan; Liu, Yunpeng; Zhang, Ye; Hu, Xuejun

doi:10.1016/j.biocel.2020.105716

Cited by 19 publications

(13 citation statements)

References 28 publications

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“…Lung cancer was the most commonly diagnosed cancer in 2018, accounting for nearly 20% of cancer deaths that year [ 1 ]. Lung adenocarcinoma (LUAD) is a predominant pathologic subtype of lung cancer [ 2 ]. Despite progress in comprehensive therapies, including surgery, radiotherapy, and targeted therapy, over the past 20 years, the OS of LUAD patients remains poor [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

et al. 2021

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Background Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. Methods The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. Results In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. Conclusions In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.

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Section: Introductionmentioning

confidence: 99%

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

et al. 2021

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“…Furthermore, GPSM2 also plays a vital role in cell division symmetry control and in the G2/M phase of the cell cycle [45,46]. Cancer-related research has revealed that GPSM2 could potentially serve as a drug target and prognostic biomarker in hepatocellular carcinoma [47], lung adenocarcinoma [48], and pancreatic cancer [13]. GPSM2 was first reported to be highly over-expressed in breast cancer and play a crucial role in cytokinesis by Fukukawa et al [8].…”

Section: Discussionmentioning

confidence: 99%

Identifying GPSM Family Members as Potential Biomarkers in Breast Cancer: A Comprehensive Bioinformatics Analysis

Dang

Nguyen

et al. 2021

Biomedicines

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G-protein signaling modulators (GPSMs) are a class of proteins involved in the regulation of G protein-coupled receptors, the most abundant family of cell-surface receptors that are crucial in the development of various tumors, including breast cancer. This study aims to identify the potential therapeutic and prognostic roles of GPSMs in breast cancer. Oncomine and UALCAN databases were queried to determine GPSM expression levels in breast cancer tissues compared to normal samples. Survival analysis was conducted to reveal the prognostic significance of GPSMs in individuals with breast cancer. Functional enrichment analysis was performed using cBioPortal and MetaCore platforms. Finally, the association between GPSMs and immune infiltration cells in breast cancer was identified using the TIMER server. The experimental results then showed that all GPSM family members were significantly differentially expressed in breast cancer according to Oncomine and UALCAN data. Their expression levels were also associated with advanced tumor stages, and GPSM2 was found to be related to worse distant metastasis-free survival in patients with breast cancer. Functional enrichment analysis indicated that GPSMs were largely involved in cell division and cell cycle pathways. Finally, GPSM3 expression was correlated with the infiltration of several immune cells. Members of the GPSM class were differentially expressed in breast cancer. In conclusion, expression of GPSM2 was linked with worse distant metastasis-free outcomes, and hence could potentially serve as a prognostic biomarker. Furthermore, GPSM3 has potential to be a possible target for immunotherapy for breast cancer.

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“…Early diagnosis of LUAD is challenging because of the lack of early biomarkers and symptoms. Consequentially, local progression likely ensues by the time patients exhibit symptoms and receive a differential diagnosis, missing the optimal time for surgical treatment (5)(6)(7). Exploring prognostic methods specific to LUAD patients is urgently needed to provide personalized treatment and management plans.…”

Section: Introductionmentioning

confidence: 99%

CD8+ T Cell-Associated Gene Signature Correlates With Prognosis Risk and Immunotherapy Response in Patients With Lung Adenocarcinoma

Zhang

Guo

et al. 2022

Front. Immunol.

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The presence of infiltrating CD8+ T lymphocytes in the tumor microenvironment of lung adenocarcinoma (LUAD) is correlated with improved patient prognosis, but underlying regulatory mechanisms remain unknown. To identify biomarkers to improve early diagnosis and treatment of LUAD, we downloaded 13 immune cell line-associated datasets from the GEO database. We identified CD8+ T cell-associated genes via weighted correlation network analysis. We constructed molecular subtypes based on CD8+ T cell-associated genes and constructed a multi-gene signature. We identified 252 CD8+ T cell-associated genes significantly enriched in immune function-related pathways and two molecular subtypes of LUAD (immune cluster 1 [IC1] and IC2) using our CD8+ T cell-associated gene signature. Patients with the IC2 subtype had a higher tumor mutation burden and lower immune infiltration scores, whereas those with the IC1 subtype were more sensitive to immune checkpoint inhibitors. Prioritizing the top candidate genes to construct a 10-gene signature, we validated our model using independent GSE and TCGA datasets to confirm its robustness and stable prognostic ability. Our risk model demonstrated good predictive efficacy using the Imvigor210 immunotherapy dataset. Thus, we established a novel and robust CD8+ T cell-associated gene signature, which could help assess prognostic risk and immunotherapy response in LUAD patients.

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Loss of G-protein-signaling modulator 2 accelerates proliferation of lung adenocarcinoma via EGFR signaling pathway

Cited by 19 publications

References 28 publications

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma

Identifying GPSM Family Members as Potential Biomarkers in Breast Cancer: A Comprehensive Bioinformatics Analysis

CD8+ T Cell-Associated Gene Signature Correlates With Prognosis Risk and Immunotherapy Response in Patients With Lung Adenocarcinoma

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