RACK1 是口腔鳞状细胞癌中具有器官特异性的预后预测因子。

RACK1 is an organ-specific prognostic predictor in OSCC.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Oral Oncol. 2018 Jan;76:22-26. doi: 10.1016/j.oraloncology.2017.10.025. Epub 2017 Nov 29.

DOI:10.1016/j.oraloncology.2017.10.025

PMID:29290282

Abstract

OBJECTIVES

This study aims to verify that RACK1 is an organ-specific prognostic predictor in patients with oral squamous cell carcinoma (OSCC).

EXPERIMENTAL DESIGN

The RACK1 expression level was assessed by immunohistochemistry (IHC) in a total of 342 OSCC patients from 3 independent cohorts. The multivariate hazard ratios for Overall Survival (OS) was determined by Cox proportional hazards regression model. OS was analyzed in 460 Head Neck Squamous Cell Carcinoma (HNSCC) patients from TCGA data set. The expression level of RACK1 was analyzed in 60 cases multiple organ tissue microarrays representing both normal and cancer tissues by IHC, and in TCGA database of mRNA abundance in cancers and paired normal tissues.

RESULTS

The median follow-up times of patients in the study was 74, 52, and 78 months. High expression of RACK1 was identified in tumors from 103 of 151 patients (68.2%), 51 of 83 patients (61.4%), and 59 of 108 patients (54.6%). Compared with low expression, high expression of RACK1 was strongly associated with worse OS, with HR of 0.5995 (95% CI, 0.3929 to 0.9147; P=0.0176), 0.4402 (95% CI, 0.2321 to 0.8348; P=0.0120), and 0.5010 (95% CI, 0.2886 to 0.8699; P=0.0141). This finding is consistent with TCGA HNSCC data (P=0.0276). Tissue microarrays analyses showed different protein expression level of RACK1 in multiple human carcinomas and this finding is consistent with the TCGA database analysis of RACK1 mRNA abundance.

CONCLUSION

Our findings demonstrated that RACK1 is a good independent organ-specific predictor of the risk of death in OSCC.

摘要

目的

本研究旨在验证 RACK1 是口腔鳞状细胞癌（OSCC）患者的器官特异性预后预测因子。

实验设计

通过免疫组织化学（IHC）在来自 3 个独立队列的总共 342 名 OSCC 患者中评估 RACK1 的表达水平。通过 Cox 比例风险回归模型确定总生存期（OS）的多变量风险比。通过 TCGA 数据集分析 460 名头颈部鳞状细胞癌（HNSCC）患者的 OS。通过 IHC 分析 60 例代表正常和癌症组织的多器官组织微阵列中 RACK1 的表达水平，并在 TCGA 数据库中分析癌症和配对正常组织中的 mRNA 丰度。

结果

研究中患者的中位随访时间分别为 74、52 和 78 个月。在 151 名患者中的 103 名（68.2%）、83 名患者中的 51 名（61.4%）和 108 名患者中的 59 名（54.6%）肿瘤中鉴定出 RACK1 的高表达。与低表达相比，RACK1 的高表达与较差的 OS 密切相关，HR 为 0.5995（95%CI，0.3929 至 0.9147；P=0.0176）、0.4402（95%CI，0.2321 至 0.8348；P=0.0120）和 0.5010（95%CI，0.2886 至 0.8699；P=0.0141）。这一发现与 TCGA HNSCC 数据一致（P=0.0276）。组织微阵列分析显示 RACK1 在多种人类癌中的蛋白表达水平不同，这一发现与 TCGA 数据库中 RACK1 mRNA 丰度的分析一致。