一种用于口腔鳞状细胞癌的新型免疫预后生物标志物，与肿瘤免疫微环境中的表达相关。

: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to expression in the tumor immune microenvironment.

作者信息

Chen Zheng, Chen Qiang, Li Shuai, Tu Shaoqin, Chen Qiongyu, Wang Anxun

机构信息

Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Stomatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Ann Transl Med. 2022 Feb;10(3):144. doi: 10.21037/atm-21-6915.

DOI:10.21037/atm-21-6915

PMID:35284546

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8904997/

Abstract

BACKGROUND

This study aimed to screen and identify potential immune biomarker to predict the prognosis of oral squamous cell carcinoma (OSCC).

METHODS

Data of OSCC patient from The Cancer Genome Atlas (TCGA) database were downloaded, and the ESTIMATE algorithm was used to calculate stromal and immune scores. Differentially expressed genes (DEGs) between the high and low immune score groups were screened, and Kaplan-Meier survival analysis was performed to identify the DEGs linked to the overall survival (OS) time of OSCC patients. Then, those DEGs were validated in anther cohort. A correlation analysis was used to further screen the prognostic genes which were tightly linked to the expression of programmed cell death 1 ()/programmed death-ligand 1 (). The expression profiles of the candidate genes interleukin 12 receptor subunit beta 1 (), cytotoxic T-lymphocyte associated protein 4 (), and G protein-coupled receptor 25 () were identified in the single-cell RNA sequence OSCC dataset from GSE103322. Finally, immunohistochemistry (IHC) and immunofluorescence (IF) were applied to confirm the expression pattern of in OSCC tissue microarray. Kaplan-Meier analysis was used to assess the prognostic significance of staining score in the malignant and non-malignant cells among the patients.

RESULTS

The high immune score group showed better OS compared with that of the low immune scores group. Among 339 DEGs, 90 were identified as being tightly linked to OS time. In the validation set, 23 genes were confirmed to be closely associated with survival prognosis, and the expression levels of , , and were commonly associated with the expression of /. The RNA-sequencing showed that was expressed in epithelial and immune cells, whereas and were relatively poorly expressed in the OSCC tissue. IHC showed that was positively expressed in both malignant and non-malignant cells. IF showed that IL-12RB1 was co-expressed with , , , and PD-L1 on the cytomembrane. Additionally, high score of expression in the non-malignant cells was a prognostic risk factor for OS of OSCC.

CONCLUSIONS

was tightly associated with survival of OSCC and with the expression levels of / in the tumor immune microenvironment.

摘要

背景

本研究旨在筛选和鉴定潜在的免疫生物标志物以预测口腔鳞状细胞癌（OSCC）的预后。

方法

下载来自癌症基因组图谱（TCGA）数据库的OSCC患者数据，并使用ESTIMATE算法计算基质和免疫评分。筛选高免疫评分组和低免疫评分组之间的差异表达基因（DEG），并进行Kaplan-Meier生存分析以鉴定与OSCC患者总生存（OS）时间相关的DEG。然后，在另一个队列中验证这些DEG。使用相关性分析进一步筛选与程序性细胞死亡1（PD-1）/程序性死亡配体1（PD-L1）表达紧密相关的预后基因。在来自GSE103322的单细胞RNA序列OSCC数据集中鉴定候选基因白细胞介素12受体亚基β1（IL-12RB1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和G蛋白偶联受体25（GPR25）的表达谱。最后，应用免疫组织化学（IHC）和免疫荧光（IF）来确认IL-12RB1在OSCC组织芯片中的表达模式。使用Kaplan-Meier分析评估患者中恶性和非恶性细胞中IL-12RB1染色评分的预后意义。

结果

高免疫评分组的OS优于低免疫评分组。在339个DEG中，90个被鉴定为与OS时间紧密相关。在验证集中，23个基因被证实与生存预后密切相关，且IL-12RB1、CTLA-4和GPR25的表达水平通常与PD-1/PD-L1的表达相关。RNA测序显示IL-12RB1在上皮细胞和免疫细胞中表达，而CTLA-4和GPR25在OSCC组织中表达相对较低。IHC显示IL-12RB1在恶性和非恶性细胞中均呈阳性表达。IF显示IL-12RB1在细胞膜上与CD3、CD4、CD8和PD-L1共表达。此外，非恶性细胞中IL-12RB1高表达是OSCC患者OS的预后危险因素。