Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

Guofu Lin; Luyang Chen; Lanlan Lin; Hai Lin; Zhifeng Guo; Yingxuan Xu; Chanchan Hu; Jinglan Fu; Qinhui Lin; Wenhan Chen; Yiming Zeng; Yuan Xu

doi:10.3389/fmolb.2021.736367

Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

Front Mol Biosci. 2021 Oct 11:8:736367. doi: 10.3389/fmolb.2021.736367. eCollection 2021.

Authors

Guofu Lin^{1

2

3}, Luyang Chen^{1

2

3}, Lanlan Lin^{1

2

3}, Hai Lin^{1

2

3}, Zhifeng Guo^{1

2

3}, Yingxuan Xu^{1

2

3}, Chanchan Hu⁴, Jinglan Fu^{1

2}, Qinhui Lin^{1

2}, Wenhan Chen^{1

2

3}, Yiming Zeng^{1

2}, Yuan Xu^{1

2}

Affiliations

¹ Department of Respiratory Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
² Respiratory Medicine Center of Fujian Province, Quanzhou, China.
³ The Second Clinical College, Fujian Medical University, Fuzhou, China.
⁴ Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated. Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan-Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD. Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan-Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD. Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

Keywords: RNA sequencing; aquaporin family; bioinformatics analysis; lung adenocarcinoma; prognosis.