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SPARCL1、Shp2、MSH2、E-钙黏蛋白、p53、ADCY-2 和 MAPK 在结直肠癌中与预后相关。

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer.

机构信息

Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2011 Apr 21;17(15):2028-36. doi: 10.3748/wjg.v17.i15.2028.

Abstract

AIM

To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients.

METHODS

One hundred and fifty-six CRC patients were followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers.

RESULTS

Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage II/III patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001).

CONCLUSION

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

摘要

目的

研究与结直肠癌(CRC)患者预后相关的标志物的表达情况。

方法

对 156 例接受根治性手术后随访时间超过 3 年的 CRC 患者进行研究。采用免疫组织化学(IHC)分析检测 14 种通路相关标志物(p53、APC、p21ras、E-cadherin、内皮素-B 受体、Shp2、ADCY-2、SPARCL1、神经粘连蛋白 1、hsp27、mmp-9、MAPK、MSH2 和 rho)在这些患者标本中的表达情况。利用支持向量机(SVM)的生物信息学分析,从这些标志物的组合中确定最佳的预后模型。

结果

7 个标志物(SPARCL1、Shp2、MSH2、E-cadherin、p53、ADCY-2 和 MAPK)与 CRC 患者的预后和临床病理特征显著相关(P<0.05)。通过 SVM 从这 7 个标志物的组合中建立了预后模型,结果表明该模型能够区分生存情况不同的患者,特别是在 II/III 期患者中。根据最佳预后模型,p53/SPARCL1 模型中,高表达 p53 和低表达 SPARCL1 的患者 3 年生存率较其他患者低约 50%(P<0.001)。

结论

SPARCL1、Shp2、MSH2、E-cadherin、p53、ADCY-2 和 MAPK 是 CRC 潜在的预后标志物。p53/SPARCL1 生物信息学模型可以作为肿瘤-淋巴结-转移分期的补充。

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