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

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.

• Authors: Yang Wang, Bo He, Yan Dong, Gong-Jing He, Xiao-Wei Qi, Yan Li, Yi-Fei Yang, Yu Rao, Zhong-Shun Cen, Fei Han, Jun Ding, Jian-Jun Li
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 31 Issue 3 Pg. 239-254 ( 2021) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 33896818 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Homeodomain Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• homeobox protein HOXA13

Topics

• Animals
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Proliferation (physiology)
• Gene Expression
• Heterografts
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Prognosis
• Transfection
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Wnt Signaling Pathway