Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer

Article type: Research Article

Authors: Wang, Yang^{a; 1} | He, Bo^{b; 1} | Dong, Yan^c | He, Gong-Jing^d | Qi, Xiao-Wei^e | Li, Yan^f | Yang, Yi-Fei^a | Rao, Yu^a | Cen, Zhong-Shun^a | Han, Fei^{g; *} | Ding, Jun^{h; *} | Li, Jian-Jun^{c; *}

Affiliations: [a] Department of Pediatrics, Southwest Hospital, Army Medical University, Chongqing, China | [b] Department of Thoracic Surgery, Southwest Hospital, Army Medical University, Chongqing, China | [c] Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China | [d] Department of Otolaryngology, Southwest Hospital, Army Medical University, Chongqing, China | [e] Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, China | [f] Chongqing University Cancer Hospital, Chongqing, China | [g] Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China | [h] Department of Hepatobiliary Surgery, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China

Correspondence: [*] Corresponding authors: Fei Han, Jun Ding and Jian-Jun Li, No. 30, Gaotanyan Street, Shapingba District, Chongqing 400038, China. %****␣cbm-31-cbm200540_temp.tex␣Line␣125␣**** Tel.: +86 23 68772390 and +86 23 68765193; Fax: +86 23 65425219; E-mail: flysky@tmmu.edu.cn/han16897723@163.com(FeiHan),2223407767@QQ.com(JunDing)andjianjunli@tmmu.edu.cn(Jian-JunLi).

Note: [1] Co-first authors.

Abstract: BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.

Keywords: Overall survival, diagnostic marker, homeobox-A13, oncogene, P53 signaling, Wnt/β-catenin signaling, non-small cell lung cancer

DOI: 10.3233/CBM-200540

Journal: Cancer Biomarkers, vol. 31, no. 3, pp. 239-254, 2021