Combined lysosomal protein transmembrane 4 beta-35 and argininosuccinate synthetase expression predicts clinical outcome in hepatocellular carcinoma patients

Combined lysosomal protein transmembrane 4 beta-35 and argininosuccinate synthetase expression predicts clinical outcome in hepatocellular carcinoma patients
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DOI:
10.1007/s00595-010-4338-5
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发表时间:
2011-06-01
期刊:
影响因子:
2.5
通讯作者:
Zhou, Rouli
Zhou, Rouli
中科院分区:
医学4区
文献类型:
--
作者:
Yang, Hua;Lin, Ming;Zhou, Rouli

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新发现的溶酶体跨膜蛋白4 β-35(LAPTM 4 B-35)在肿瘤进展和转移中起重要作用,而精氨酸琥珀酸合成酶(ASS)提供精氨酸作为肝细胞癌(HCC)不可或缺的营养素。为探讨LAPTM 4 B-35和ASS在HCC患者中的共表达对判断预后的临床意义,采用免疫组化方法检测71例HCC组织和配对的非癌肝组织中LAPTM 4 B-35和ASS的表达。采用卡方检验评估LAPTM 4 B-35和ASS表达与选定临床病理参数的相关性。通过Kaplan-Meier方法和对数秩检验确定患者生存率和生存率差异。多因素分析采用考克斯回归分析,LAPTM 4 B-35和ASS的联合表达与TNM分期、门静脉浸润密切相关。此外,同时表达LAPTM 4 B-35和ASS的HCC患者的总生存期(OS)和无病生存期(DFS)均明显较差(均P < 0.001)。多因素分析显示,LAPTM 4 B-35和ASS的联合表达是影响肝细胞癌患者OS和DFS的独立预后因素(分别为P = 0.039和P = 0.035),LAPTM 4 B-35过表达联合ASS的阳性表达是肝细胞癌患者预后不良的指标。
The newly-identified lysosomal protein transmembrane 4 beta-35 (LAPTM4B-35) plays important roles in tumor progression and metastasis, while argininosuccinate synthetase (ASS) provides arginine as an indispensable nutrient for hepatocellular carcinoma (HCC). The present study investigated the clinical significance of the coexpression of LAPTM4B-35 and ASS in HCC patients on determining the prognosis.Immunohistochemistry was used to evaluate the expression of LAPTM4B-35 and ASS in HCC tissues and paired noncancerous liver samples from 71 patients. The correlation of combined LAPTM4B-35 and ASS expression with selected clinicopathologic parameters was assessed with the chi-squared test. Patient survival and differences in survival were determined by the Kaplan-Meier method and the log-rank test. A Cox regression analysis was adopted for a multivariate analysis of the prognostic factors.Combined LAPTM4B-35 and ASS expression was significantly associated with TNM stage and portal vein invasion. In addition, patients with HCCs expressing both LAPTM4B-35 and ASS exhibited both markedly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001). According to the multivariate analyses, combined LAPTM4B-35 and ASS expression was found to be an independent prognostic factor for OS and DFS (P = 0.039 and P = 0.035, respectively).The overexpression of LAPTM4B-35 in combination with positive ASS expression is a negative prognostic marker for HCC.