SOX9 在肾细胞癌、膀胱癌和阴茎癌中的表达及临床意义。

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer.

出版信息

Oncol Res Treat. 2017;40(1-2):15-20. doi: 10.1159/000455145. Epub 2017 Jan 25.

Abstract

BACKGROUND

Novel molecular markers are important diagnostic tools for the assessment of cancer progression and evaluation of effectiveness of the treatment. SOX9, a key regulator of developmental processes, is overexpressed in various neoplasms, such as prostate, breast, and colorectal cancers. However, the utilization of SOX9 as a biomarker for other urological cancers has not yet been investigated.

METHODS

In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the SOX9 protein expression was quantitated as immunoreactive scores in patients with renal cell carcinoma (RCC), bladder cancer (BCa), and penile cancer (PC).

RESULTS

In comparison with normal tissues, SOX9 protein expression was signiﬁcantly upregulated in RCC (p < 0.001) and BCa (p < 0.001), and significantly correlated with the advanced pathological grade (RCC: p = 0.023) and clinical stage (RCC: p = 0.022 and BCa: p = 0.046) of patients. Based on the mRNA level in the TCGA dataset, SOX9 was upregulated in RCC with gender (p = 0.027), advanced pathological grade (p = 0.003) and advanced clinical stage (p = 0.001). Kaplan-Meier survival curves revealed that RCC patients with high SOX9 levels had shorter survival (p < 0.001). Further, high SOX9 expression was an independent prognostic factor for RCC patients (hazard ratio 0.056, 95% confidence interval 0.607-1.184; p < 0.001).

CONCLUSION

These findings suggest that SOX9 may play an important role in tumor progression of RCC and BCa and it may be used as a biomarker of this malignancy.

摘要

背景

新型分子标志物是评估癌症进展和评估治疗效果的重要诊断工具。SOX9 是发育过程的关键调节因子，在各种肿瘤中过度表达，如前列腺癌、乳腺癌和结直肠癌。然而，SOX9 作为其他泌尿系统癌症的生物标志物尚未得到研究。

方法

本研究通过免疫组织化学分析了配对的患者组织微阵列，并用免疫反应评分定量了肾细胞癌（RCC）、膀胱癌（BCa）和阴茎癌（PC）患者中 SOX9 蛋白的表达。

结果

与正常组织相比，SOX9 蛋白在 RCC（p<0.001）和 BCa（p<0.001）中表达显著上调，并且与高级别病理分级（RCC：p=0.023）和临床分期（RCC：p=0.022 和 BCa：p=0.046）显著相关。基于 TCGA 数据集的 mRNA 水平，SOX9 在 RCC 中随性别（p=0.027）、高级别病理分级（p=0.003）和高级别临床分期（p=0.001）而上调。Kaplan-Meier 生存曲线显示，SOX9 水平高的 RCC 患者生存时间较短（p<0.001）。此外，SOX9 高表达是 RCC 患者的独立预后因素（风险比 0.056，95%置信区间 0.607-1.184；p<0.001）。