Low Expression of ADCY4 Predicts Worse Survival of Lung Squamous Cell Carcinoma Based on Integrated Analysis and Immunohistochemical Verification

Zhicong Liu; Lixin Ru; Zhenchao Ma; Zhenchao Ma

doi:10.3389/fonc.2021.637733

Frontiers in Oncology (Jun 2021)

Low Expression of ADCY4 Predicts Worse Survival of Lung Squamous Cell Carcinoma Based on Integrated Analysis and Immunohistochemical Verification

Zhicong Liu,
Lixin Ru,
Zhenchao Ma,
Zhenchao Ma

Affiliations

Zhicong Liu: Department of Respiratory Medicine, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
Lixin Ru: Department of Radiation Oncology, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
Zhenchao Ma: Department of Radiation Oncology, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
Zhenchao Ma: Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China

DOI: https://doi.org/10.3389/fonc.2021.637733
Journal volume & issue: Vol. 11

Abstract

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PurposeThe molecular mechanism underlying the carcinogenesis and development of lung squamous cell carcinoma (LUSC) has not been sufficiently elucidated. This analysis was performed to find pivotal genes and explore their prognostic roles in LUSC.MethodsA microarray dataset from GEO (GSE19188) and a TCGA-LUSC dataset were used to identify differentially co-expressed genes through Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis. We conducted functional enrichment analyses of differentially co-expressed genes and established a protein-protein interaction (PPI) network. Then, we identified the top 10 hub genes using the Maximal Clique Centrality (MCC) algorithm. We performed overall survival (OS) analysis of these hub genes among LUSC cases. GSEA analyses of survival-related hub genes were conducted. Ultimately, the GEO and The Human Protein Atlas (THPA) databases and immunohistochemistry (IHC) results from the real world were used to verify our findings.ResultsA list of 576 differentially co-expressed genes were selected. Functional enrichment analysis indicated that regulation of vasculature development, cell−cell junctions, actin binding and PPAR signaling pathways were mainly enriched. The top 10 hub genes were selected according to the ranking of MCC scores, and 5 genes were closely correlated with OS of LUSC. Additionally, GSEA analysis showed that spliceosome and cell adhesion molecules were associated with the expression of GNG11 and ADCY4, respectively. The GSE30219 and THPA databases and IHC results from the real world indicated that although GNG11 was not detected, ADCY4 was obviously downregulated in LUSC tissues at the mRNA and protein levels.ConclusionsThis analysis showed that survival-related hub genes are highly correlated to the tumorigenesis and development of LUSC. Additionally, ADCY4 is a candidate therapeutic and prognostic biomarker of LUSC.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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