2 型乳头状肾细胞癌的预后和治疗生物标志物的鉴定。

Identification of prognostic and therapeutic biomarkers in type 2 papillary renal cell carcinoma.

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 20032, People's Republic of China.

出版信息

World J Surg Oncol. 2023 Mar 16;21(1):98. doi: 10.1186/s12957-022-02836-3.

DOI:10.1186/s12957-022-02836-3

PMID:36927438

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10022194/

Abstract

BACKGROUND

Papillary renal cell carcinoma (PRCC) can be divided into type 1 (PRCC1) and type 2 (PRCC2) and PRCC2 share a more invasive phenotype and worse prognosis. This study aims to identify potential prognostic and therapeutic biomarkers in PRCC2.

METHODS

A cohort from The Cancer Genome Atlas and two datasets from Gene Expression Omnibus were examined. Common differentially expressed genes (DEGs) were screened and potential biomarkers were explored by using Kaplan-Meier method and cox regression analysis. Functional enrichment analysis was utilized to evaluate the potential biological functions. Tumor infiltrating immune cells were estimated by CIBERSORT algorithm. Ninety-two PRCC2 samples from Fudan University Shanghai Cancer Center were obtained, and immunostaining was performed to validate prognostic and therapeutic significance of the potential biomarker.

RESULTS

PRCC2 has worse overall survival and shares distinct molecular characteristics from PRCC1. There was significant higher expression level of Targeting protein for Xklp2 (TPX2) in PRCC2 compared with normal tissues. Higher expression level of TPX2 was significantly associated with worse overall survival in PRCC2 and kinesin family genes expression were found significantly elevated in high risk PRCC2. Abundance of tumor infiltrating M1 macrophage was significantly higher in PRCC2 and it was also associated with worse overall survival. In the FUSCC cohort, higher TPX2 expression was significantly correlated with worse overall and progression-free survival. Retrospective analysis indicated that mTOR inhibitor (everolimus) had greater efficacy in the high-risk group than in the low-risk group (overall response rate: 28.6% vs. 16.7%) and that everolimus had greater efficacy than sunitinib in the high-risk group (overall response rate: 28.6% vs. 20%).

CONCLUSIONS

TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.

摘要

背景

乳头状肾细胞癌（PRCC）可分为 1 型（PRCC1）和 2 型（PRCC2），PRCC2 具有侵袭性更强的表型和更差的预后。本研究旨在鉴定 PRCC2 中的潜在预后和治疗生物标志物。

方法

本研究从癌症基因组图谱（TCGA）中选取了一个队列，并从两个基因表达综合数据库（GEO）中选取了两个数据集。通过 Kaplan-Meier 方法和 Cox 回归分析筛选出共同差异表达基因（DEGs），并利用功能富集分析来评估潜在的生物学功能。通过 CIBERSORT 算法估计肿瘤浸润免疫细胞。本研究从复旦大学附属肿瘤医院获取了 92 例 PRCC2 样本，并进行免疫组化染色以验证潜在生物标志物的预后和治疗意义。

结果

PRCC2 的总生存期更差，并且与 PRCC1 具有明显不同的分子特征。与正常组织相比，TPX2 在 PRCC2 中的表达水平显著更高。TPX2 的高表达水平与 PRCC2 的总生存期显著相关，并且在高风险 PRCC2 中发现驱动蛋白家族基因的表达显著升高。PRCC2 中的肿瘤浸润 M1 巨噬细胞丰度显著较高，并且与总生存期较差相关。在 FUSCC 队列中，TPX2 的高表达与总生存期和无进展生存期较差显著相关。回顾性分析表明，mTOR 抑制剂（依维莫司）在高危组中的疗效优于低危组（总缓解率：28.6% vs. 16.7%），并且依维莫司在高危组中的疗效优于舒尼替尼（总缓解率：28.6% vs. 20%）。