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细胞质聚腺苷酸结合蛋白1(PABPC1)高表达作为早期食管鳞状细胞癌的预后生物标志物

High-Expression of Cytoplasmic Poly (A) Binding Protein 1 (PABPC1) as a Prognostic Biomarker for Early-Stage Esophageal Squamous Cell Carcinoma.

作者信息

Pu Jiangtao, Zhang Tao, Zhang Dengguo, He Kaiming, Chen Yonghong, Sun Xingwang, Long Wenbo

机构信息

Thoracic Surgery Department of the First Affiliated Hospital, Southwest Medical University, Sichuan, People's Republic of China.

Laboratory of Affiliated Hospital of traditional Chinese medicine of Southwest Medical University, Sichuan, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Jul 5;13:5361-5372. doi: 10.2147/CMAR.S317631. eCollection 2021.

Abstract

BACKGROUND AND OBJECTIVE

Poly (A) binding protein cytoplasmic 1 (PABPC1) plays a crucial role in the regulation of RNA polyadenylation, translation initiation, and mRNA stability and may be involved in tumorigenesis. Herein, we set out to identify the prognostic value of PABPC1 expression in esophageal squamous cell carcinoma (ESCC).

METHODS

Using quantitative real-time PCR (qRT-PCR) and immunohistochemical analysis, the present study investigated mRNA and protein expressions of PABPC1 in 231 ESCCs and their paired adjacent normal epithelial tissues.

RESULTS

We observed a reduction in the average mRNA expression of in ESCC tissue specimen, but the mRNA expression of was significantly higher (P<0.001) in ESCC tissues with high PABPC1 expression and lower (P=0.033) in tissues with low PABPC1 expression. In immunohistochemical analysis, positive expression of the PABPC1 protein was identified in 179 ESCC tissue specimens (179/231, 77.5%), while the percentage of ESCC tissue specimens with high expression of PABPC1 was found to be 41.1% (95/231). PABPC1 expression was found to be significantly correlated with lymph node metastasis (LNM) (P=0.011), pathological stage (P=0.021), tumor recurrence (P<0.001), and the outcome (P<0.001) of patients with ESCC. High expression of PABPC1 was associated with poor overall survival (OS) of ESCC patients (P<0.001) among all pathological stages, particularly in the early stages (pStage-I and -II), and identified to be an independent prognostic factor for OS of patients with ESCC in multivariate analysis (HR=2.622; 95% CI, 1.68-4.129). Comparatively, the expression of Ki-67, p53, and nm23 was not associated with OS.

CONCLUSION

In this study, we discovered that PABPC1 is a prognostic biomarker and a therapeutic target for ESCC, particularly early-stage ESCC.

摘要

背景与目的

多聚腺苷酸结合蛋白胞质1(PABPC1)在RNA多聚腺苷酸化、翻译起始及mRNA稳定性调控中起关键作用,可能参与肿瘤发生。在此,我们旨在确定PABPC1表达在食管鳞状细胞癌(ESCC)中的预后价值。

方法

本研究采用定量实时聚合酶链反应(qRT-PCR)和免疫组化分析,检测231例ESCC及其配对的相邻正常上皮组织中PABPC1的mRNA和蛋白表达。

结果

我们观察到ESCC组织标本中PABPC1的平均mRNA表达降低,但在PABPC1高表达的ESCC组织中mRNA表达显著更高(P<0.001),而在PABPC1低表达的组织中更低(P=0.033)。免疫组化分析显示,179例ESCC组织标本(179/231,77.5%)中PABPC1蛋白呈阳性表达,而PABPC1高表达的ESCC组织标本比例为41.1%(95/231)。发现PABPC1表达与ESCC患者的淋巴结转移(LNM)(P=0.011)、病理分期(P=0.021)、肿瘤复发(P<0.001)及预后(P<0.001)显著相关。PABPC1高表达与ESCC患者的总生存期(OS)较差相关(P<0.001),在所有病理分期中均如此,尤其是在早期阶段(pStage-I和-II),并且在多因素分析中被确定为ESCC患者OS的独立预后因素(HR=2.622;95%CI,1.68-4.129)。相比之下,Ki-67、p53和nm23的表达与OS无关。

结论

在本研究中,我们发现PABPC1是ESCC尤其是早期ESCC的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35df/8275044/742aee847e4a/CMAR-13-5361-g0001.jpg

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