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基于Estimate算法探索甲状腺乳头状癌免疫微环境、突变负荷与预后的相关性分析

Exploring the correlation analysis of immune microenvironment, mutation burden and prognosis of papillary thyroid carcinoma based on Estimate algorithm.

作者信息

Wang Ying, He Ying, Cao Liubin, Peng Xiaoqing, Gu Zhenyong, Yan Jun

机构信息

Department of Forensic Medicine, Medical School, Nantong University, Nantong, China.

出版信息

Gland Surg. 2022 May;11(5):860-867. doi: 10.21037/gs-22-211.

Abstract

BACKGROUND

This study aimed to investigate the correlation between immune infiltration and tumor mutational burden (TMB) in papillary thyroid carcinoma.

METHODS

Transcriptome sequencing data sets, gene mutation data sets, and clinical data sets were downloaded from The Cancer Genome Atlas (TCGA) database. The immune and papillary carcinoma stromal scores were calculated using the "Estimate" package of R software. The relationship between the immune score, stromal score, TMB, and papillary thyroid carcinoma progression-free survival was analyzed. Pearson's test was used to analyze the correlation between the immune score, stromal score, and TMB.

RESULTS

The stromal score and immune score of papillary thyroid carcinoma tissue were lower than those of normal thyroid tissue (P=0.008 and P<0.001, respectively). There was no significant difference in progression-free survival between the high stromal and low stromal score groups (P=0.075). The progression-free survival of the high immune score group was better than that of the low immune score group (P=0.029), and the progression-free survival of the low TMB group was better than that of the high TMB group (P<0.001). The high immune score, low TMB group had the best prognosis (P=0.003). Univariate Cox analysis showed that age, pathological stage, and TMB were risk factors for progression-free survival [hazard ratio (HR) >1, P<0.05], and that the immune score was a protective factor for progression-free survival (HR <1, P<0.05). Multivariate Cox analysis showed that age and TMB were independent risk factors for progression-free survival (HR >1, P<0.05), and that the immune score was an independent protective factor for progression-free survival (HR <1, P<0.05). Correlation analysis showed that the immune and stromal score were both negatively correlated with TMB (r=-0.26, P=0.031 and r=-0.41, P=0.028, respectively).

CONCLUSIONS

The immune and stromal scores of papillary thyroid carcinoma were negatively correlated with TMB. Thyroid cancer gene mutations inhibit immune cell infiltration and alter the thyroid cancer microenvironment. The immune score was an independent protective factor for progression-free survival, while TMB was an independent risk factor, both of which can be used for clinical prognosis assessment. Combined immunological and genomic analysis of papillary thyroid carcinoma can reveal potential prognostic markers and therapeutic targets and provide clues for the tumor immune escape mechanism.

摘要

背景

本研究旨在探讨甲状腺乳头状癌中免疫浸润与肿瘤突变负荷(TMB)之间的相关性。

方法

从癌症基因组图谱(TCGA)数据库下载转录组测序数据集、基因突变数据集和临床数据集。使用R软件的“Estimate”包计算免疫和乳头状癌基质评分。分析免疫评分、基质评分、TMB与甲状腺乳头状癌无进展生存期之间的关系。采用Pearson检验分析免疫评分、基质评分与TMB之间的相关性。

结果

甲状腺乳头状癌组织的基质评分和免疫评分低于正常甲状腺组织(分别为P = 0.008和P < 0.001)。高基质评分组和低基质评分组的无进展生存期无显著差异(P = 0.075)。高免疫评分组的无进展生存期优于低免疫评分组(P = 0.029),低TMB组的无进展生存期优于高TMB组(P < 0.001)。高免疫评分、低TMB组预后最佳(P = 0.003)。单因素Cox分析显示,年龄、病理分期和TMB是无进展生存期的危险因素[风险比(HR)>1,P < 0.05],免疫评分是无进展生存期的保护因素(HR < 1,P < 0.05)。多因素Cox分析显示,年龄和TMB是无进展生存期的独立危险因素(HR > 1,P < 0.05),免疫评分是无进展生存期的独立保护因素(HR < 1,P < 0.05)。相关性分析显示,免疫和基质评分均与TMB呈负相关(分别为r = -0.26,P = 0.031和r = -0.41,P = 0.028)。

结论

甲状腺乳头状癌的免疫和基质评分与TMB呈负相关。甲状腺癌基因突变抑制免疫细胞浸润并改变甲状腺癌微环境。免疫评分是无进展生存期的独立保护因素,而TMB是独立危险因素,两者均可用于临床预后评估。对甲状腺乳头状癌进行联合免疫和基因组分析可揭示潜在的预后标志物和治疗靶点,并为肿瘤免疫逃逸机制提供线索。

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