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同源盒蛋白 A13 通过调节肺癌中的 P53 和 Wnt 信号通路发挥功能预后和诊断生物标志物的作用。

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

机构信息

Department of Pediatrics, Southwest Hospital, Army Medical University, Chongqing, China.

Department of Thoracic Surgery, Southwest Hospital, Army Medical University, Chongqing, China.

出版信息

Cancer Biomark. 2021;31(3):239-254. doi: 10.3233/CBM-200540.

DOI:10.3233/CBM-200540
PMID:33896818
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.

摘要

背景

肺癌患者的预后较差,缺乏有用的预后和诊断生物标志物。为了寻找新的预后和诊断标志物,我们之前发现同源盒 A13(HOXA13)是肺癌有前途的候选标志物。

目的

确定 HOXA13 的精确临床特征、预后和诊断价值、可能的作用和机制。

方法

通过实时定量 PCR、western blot 和组织微阵列探索基因表达。通过卡方检验、Kaplan-Meier 和 Cox 回归分析相关性。通过 MTS、EdU、Transwell、异种移植肿瘤和荧光素酶报告基因检测评估作用和机制。

结果

HOXA13 的表达在肿瘤中增加,并与患者的年龄相关。HOXA13 的表达与四个队列中患者的总生存率和无复发生存率不良相关。有趣的是,HOXA13 在腺癌(ADC)和鳞状细胞癌(SCC)中具有不同的预后意义,并且仅在 ADC 中是与性别和吸烟相关的预后因素。重要的是,HOXA13 可作为肺癌的诊断生物标志物,特别是 SCC。HOXA13 可以在体外促进癌细胞的增殖、迁移和侵袭,并促进体内肿瘤发生和肿瘤转移。HOXA13 通过调节肺癌中的 P53 和 Wnt/β-catenin 信号通路发挥致癌作用。

结论

HOXA13 是一种与 P53 和 Wnt/β-catenin 信号通路相关的新的预后和诊断生物标志物。

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