S1P1 和 ERp29 表达与胆囊腺癌的进展、转移和预后不良的相关性。

Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor prognosis of gallbladder adenocarcinoma.

机构信息

Department of Geriatric Surgery, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2013 Apr;12(2):189-95. doi: 10.1016/s1499-3872(13)60030-2.

DOI:10.1016/s1499-3872(13)60030-2

PMID:23558074

Abstract

BACKGROUND

Gallbladder cancer (GBC) is one of the most aggressive malignant neoplasms with an extremely poor prognosis. Early diagnosis significantly increases the survival rate. The present study was undertaken to evaluate the diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder lesions and to develop a possible alternative treatment for GBC.

METHODS

A total of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15 gallbladder polyp, and 35 chronic cholecystitis tissues were included. S1P1 and ERp29 expressions were evaluated by immunohistochemistry. The correlation between S1P1 and ERp29 expression and tumor pathological features and prognosis was analyzed.

RESULTS

S1P1 positive rate was significantly higher in gallbladder adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. On the contrary, ERp29 positive rate was significantly lower in adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative ERp29 expression showed moderate or severe atypical hyperplasia in the gallbladder epithelium. The overexpression of S1P1 or non-expression of ERp29 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis, and adenocarcinoma invasion. Univariate Kaplan-Meier analysis showed that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely associated with decreased survival rate. Multivariate Cox regression analysis showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an independent predictor of poor prognosis in gallbladder adenocarcinoma.

CONCLUSION

S1P1 overexpression or ERp29 absence is related to the carcinogenesis and progression, and may be potential biomarkers for early detection of gallbladder adenocarcinoma.

摘要

背景

胆囊癌（GBC）是一种侵袭性最强的恶性肿瘤之一，预后极差。早期诊断可显著提高生存率。本研究旨在评估鞘氨醇-1-磷酸受体 1（S1P1）和内质网蛋白 29（ERp29）在良性和恶性胆囊病变中的诊断和预后价值，并为 GBC 提供可能的替代治疗方法。

方法

共纳入 100 例胆囊腺癌、46 例癌旁组织、30 例胆囊腺瘤、15 例胆囊息肉和 35 例慢性胆囊炎组织。采用免疫组织化学法检测 S1P1 和 ERp29 的表达。分析 S1P1 和 ERp29 表达与肿瘤病理特征和预后的相关性。

结果

胆囊腺癌中 S1P1 的阳性率明显高于癌旁组织、腺瘤、息肉和慢性胆囊炎组织。相反，ERp29 在腺癌中的阳性率明显低于癌旁组织、腺瘤、息肉和慢性胆囊炎组织。S1P1 阳性或 ERp29 阴性的良性病变表现为胆囊上皮中度或重度异型增生。S1P1 的过表达或 ERp29 的缺失与肿瘤分化程度、肿瘤大小、淋巴结转移和腺癌浸润显著相关。单因素 Kaplan-Meier 分析显示，S1P1 升高（P=0.008）或 ERp29 缺失（P=0.043）与生存率降低密切相关。多因素 Cox 回归分析显示，S1P1 阳性（P=0.004）或 ERp29 阴性（P=0.029）是胆囊腺癌预后不良的独立预测因子。