The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients.
The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients.
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DOI：
10.1186/s40001-023-01058-x
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发表时间：
2023-02-20
影响因子：
4.2
通讯作者：
Xiao, Lijia
中科院分区：
文献类型：
--
作者：
Cui, Shengjin;Feng, Jingying;Tang, Xi;Lou, Shuang;Guo, Weiquan;Xiao, Xiaowei;Li, Shuping;Chen, Xue;Huan, Yu;Zhou, Yiwen;Xiao, Lijia
尽管肿瘤突变负荷（TMB）已被报道为多种癌症免疫治疗的生物标志物，但其是否能有效预测乳腺癌患者的生存预后仍不清楚。本研究通过多组研究探讨TMB的预后价值及其与免疫浸润的相关性。从TCGA数据库中获得986例乳腺癌患者的体细胞突变数据。根据TMB评分的四分位数将乳腺癌患者分为低TMB组和高TMB组。用“limma”R程序鉴定差异表达基因（DEG）。利用CIBERSORT算法估计每个样品的免疫细胞分数。利用TIMER数据库评价免疫基因的CNV与肿瘤免疫细胞浸润的相关性以及免疫细胞在乳腺癌中的预后价值。在乳腺癌中，TP 53、PIK 3CA、TTN、CDH 1等基因是最重要的突变基因。低TMB组患者生存率较高。在排名前10位的DEG中，有3个属于KRT基因家族。GSEA富集分析显示MAPK、Hedgehog、mTOR、TGF-β和GnRH信号通路在低TMB组中富集。低TMB组大部分免疫细胞浸润程度高于对照组（P < 0.01）。CCL 18和TRGC 1的高表达与预后不良相关。具有CCL 18拷贝数变异的乳腺癌患者，特别是臂水平增益，表现出显著降低的免疫细胞浸润。低B细胞浸润组乳腺癌患者生存预后差。TMB是乳腺癌潜在的预后标志物。免疫相关基因CCL 18和TRGC 1是预后不良的生物标志物，而免疫（B细胞）浸润是预后良好的生物标志物。
Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies. The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the “limma” R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer. In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P < 0.01). Higher expression of CCL18 and TRGC1 was correlated with poor prognosis. Breast cancer patients with CCL18 copy number variations, especially arm-level gains, showed significantly decreased immune cell infiltration. In the low B cell infiltration group, the survival prognosis of breast cancer patients was poor. TMB is a potential prognosis marker in breast cancer. Immune-related gene CCL18 and TRGC1 are biomarkers of poor prognosis while immune (B cell) infiltration is a biomarker of good prognosis.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
影响因子：
11.5
作者：
Olivier, M;Langerod, A;Borresen-Dale, AL
通讯作者：
Borresen-Dale, AL
影响因子：
--
作者：
Kim N;Hong Y;Kwon D;Yoon S
通讯作者：
Yoon S
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators