Penetrating Exploration of Prognostic Correlations of the FKBP Gene Family with Lung Adenocarcinoma

Chin-Chou Wang; Wan-Jou Shen; Gangga Anuraga; Yu-Hsiu Hsieh; Hoang Dang Khoa Ta; Do Thi Minh Xuan; Chiu-Fan Shen; Chih-Yang Wang; Wei-Jan Wang

doi:10.3390/jpm13010049

Penetrating Exploration of Prognostic Correlations of the FKBP Gene Family with Lung Adenocarcinoma

J Pers Med. 2022 Dec 26;13(1):49. doi: 10.3390/jpm13010049.

Authors

Chin-Chou Wang^{1

2

3}, Wan-Jou Shen⁴, Gangga Anuraga^{5

6

7}, Yu-Hsiu Hsieh⁴, Hoang Dang Khoa Ta^{5

6}, Do Thi Minh Xuan⁵, Chiu-Fan Shen¹, Chih-Yang Wang^{5

6

8}, Wei-Jan Wang^{4

9}

Affiliations

¹ Divisions of Pulmonary & Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
² Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
³ Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan.
⁴ Department of Biological Science and Technology, China Medical University, Taichung 40676, Taiwan.
⁵ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
⁶ Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
⁷ Department of Statistics, Faculty of Science and Technology, Universitas PGRI Adi Buana, Surabaya 60234, East Java, Indonesia.
⁸ TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁹ Research Center for Cancer Biology, China Medical University, Taichung 40676, Taiwan.

Abstract

The complexity of lung adenocarcinoma (LUAD), the development of which involves many interacting biological processes, makes it difficult to find therapeutic biomarkers for treatment. FK506-binding proteins (FKBPs) are composed of 12 members classified as conservative intracellular immunophilin family proteins, which are often connected to cyclophilin structures by tetratricopeptide repeat domains and have peptidyl prolyl isomerase activity that catalyzes proline from residues and turns the trans form into the cis form. Since FKBPs belong to chaperone molecules and promote protein folding, previous studies demonstrated that FKBP family members significantly contribute to the degradation of damaged, misfolded, abnormal, and foreign proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. In this research, we adopted high-throughput bioinformatics technology to analyze FKBP family genes in LUAD to provide credible information to clinicians and promote the development of novel cancer target drugs in the future. The current data revealed that the messenger (m)RNA levels of FKBP2, FKBP3, FKBP4, FKBP10, FKBP11, and FKBP14 were overexpressed in LUAD, and FKBP10 had connections to poor prognoses among LUAD patients in an overall survival (OS) analysis. Based on the above results, we selected FKBP10 to further conduct a comprehensive analysis of the downstream pathway and network. Through a DAVID analysis, we found that FKBP10 was involved in mitochondrial electron transport, NADH to ubiquinone transport, mitochondrial respiratory chain complex I assembly, etc. The MetaCore pathway analysis also indicated that FKBP10 was involved in "Ubiquinone metabolism", "Translation_(L)-selenoaminoacid incorporation in proteins during translation", and "Transcription_Negative regulation of HIF1A function". Collectively, this study revealed that FKBP family members are both significant prognostic biomarkers for lung cancer progression and promising clinical therapeutic targets, thus providing new targets for treating LUAD patients.

Keywords: FKBP family genes; bioinformatics; lung cancer; metabolism; prognosis.

Abstract

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