Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma.
Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma.
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DOI：
10.3892/ol.2016.5304
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发表时间：
2016-12
期刊：
影响因子：
2.9
通讯作者：
Naito Z
中科院分区：
文献类型：
--
作者：
Takata H;Kudo M;Yamamoto T;Ueda J;Ishino K;Peng WX;Wada R;Taniai N;Yoshida H;Uchida E;Naito Z
完全切除肿瘤后，肝细胞癌（HCC）的预后不佳。本研究的目的是鉴定一种能够通过全面的蛋白质分析预测 HCC 预后的分子，并阐明其临床病理学意义。通过液相色谱-串联质谱法对 HCC 进行全面的蛋白质分析。通过对 HCC 和非 HCC 组织中差异表达的蛋白质进行生物信息学分析，蛋白质二硫键异构酶 A3 (PDIA3) 被确定为预测预后的候选者。随后通过免疫染色检查了 86 例 HCC 病例中的 PDIA3 表达，并评估了 PDIA3 表达水平与临床病理特征之间的关联。采用免疫染色和末端脱氧核苷酸转移酶dUTP缺口末端标记法检测24例癌细胞的Ki-67指数和细胞凋亡情况。结果表明PDIA3在所有86例HCC病例中均有表达； 56例HCC病例（65%）表现出PDIA3高表达，30例（35%）表现出低表达。 PDIA3高表达的HCC患者的无病生存时间和总生存时间显着短于低表达的HCC患者。此外，PDIA3 表达增加与 Ki-67 指数升高相关，表明癌细胞增殖增加和凋亡细胞死亡减少。综上所述，这些结果表明 PDIA3 表达与 HCC 中的肿瘤增殖和细胞凋亡减少相关，并且 PDIA3 表达增加预示预后不良。因此，PDIA3 可能是开发 HCC 患者新型靶向疗法的关键分子。
The prognosis of hepatocellular carcinoma (HCC) is unfavorable following complete tumor resection. The aim of the present study was to identify a molecule able to predict HCC prognosis through comprehensive protein profiling and to elucidate its clinicopathological significance. Comprehensive protein profiling of HCC was performed by liquid chromatography-tandem mass spectrometry. Through the bioinformatic analysis of proteins expressed differentially in HCC and non-HCC tissues, protein disulfide-isomerase A3 (PDIA3) was identified as a candidate for the prediction of prognosis. PDIA3 expression was subsequently examined in 86 cases of HCC by immunostaining and associations between PDIA3 expression levels and clinicopathological characteristics were evaluated. The Ki-67 index and apoptotic cell death of carcinoma cells were examined by immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay in 24 cases. The results demonstrated that PDIA3 was expressed in all 86 HCC cases; 56 HCC cases (65%) exhibited high expression of PDIA3 and 30 (35%) exhibited low expression. The disease-free and overall survival times of HCC patients with high PDIA3 expression were significantly shorter than in HCC patients with low expression. Furthermore, increased expression of PDIA3 was associated with an elevated Ki-67 index, indicating increased cancer cell proliferation and a reduction in apoptotic cell death. Taken together, these results suggest that PDIA3 expression is associated with tumor proliferation and decreased apoptosis in HCC, and that increased expression of PDIA3 predicts poor prognosis. PDIA3 may therefore be a key molecule in the development of novel targeting therapies for patients with HCC.