Association of RYR2 Mutation With Tumor Mutation Burden, Prognosis, and Antitumor Immunity in Patients With Esophageal Adenocarcinoma.
Association of RYR2 Mutation With Tumor Mutation Burden, Prognosis, and Antitumor Immunity in Patients With Esophageal Adenocarcinoma.
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DOI：
10.3389/fgene.2021.669694
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发表时间：
2021
影响因子：
3.7
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Liu Z;Liu L;Jiao D;Guo C;Wang L;Li Z;Sun Z;Zhao Y;Han X
背景：食管腺癌（EAC）仍然是全球癌症相关死亡的主要原因，并且在西方国家发病率呈显著上升趋势。近期，免疫疗法极大地改变了许多晚期癌症的治疗格局，但到目前为止，其在EAC中的获益仅限于一小部分患者。
方法：利用癌症基因组图谱（TCGA）和国际癌症基因组联盟的体细胞突变数据，我们描绘了来自美国和英国的EAC患者的体细胞突变情况。基于TCGA队列的表达数据，运用多种生物信息学算法进行功能注释、免疫细胞浸润分析以及免疫疗法反应评估。
结果：我们发现RYR2是两个队列中常见的频繁突变基因，RYR2突变的患者显示出更高的肿瘤突变负荷（TMB）、更好的预后以及免疫检查点的高表达。此外，RYR2突变上调了与免疫反应相关的信号通路，并增强了EAC中的抗肿瘤免疫。多种用于评估免疫疗法反应的生物信息学算法表明，RYR2突变的患者可能从免疫疗法中获益更多。为了给不同RYR2状态的抗肿瘤治疗提供额外参考，我们确定了9种与EAC中RYR2状态相关的潜在抗肿瘤药物。
结论：本研究揭示了一个新的基因，其突变可作为EAC患者预后、TMB以及免疫疗法的潜在生物标志物。
Background: Esophageal adenocarcinoma (EAC) remains a leading cause of cancer-related deaths worldwide and demonstrates a predominant rising incidence in Western countries. Recently, immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, with the benefit in EAC thus far been limited to a small fraction of patients. Methods: Using somatic mutation data of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium, we delineated the somatic mutation landscape of EAC patients from US and England. Based on the expression data of TCGA cohort, multiple bioinformatics algorithms were utilized to perform function annotation, immune cell infiltration analysis, and immunotherapy response assessment. Results: We found that RYR2 was a common frequently mutated gene in both cohorts, and patients with RYR2 mutation suggested higher tumor mutation burden (TMB), better prognosis, and superior expression of immune checkpoints. Moreover, RYR2 mutation upregulated the signaling pathways implicated in immune response and enhanced antitumor immunity in EAC. Multiple bioinformatics algorithms for assessing immunotherapy response demonstrated that patients with RYR2 mutation might benefit more from immunotherapy. In order to provide additional reference for antitumor therapy of different RYR2 status, we identified nine latent antitumor drugs associated with RYR2 status in EAC. Conclusion: This study reveals a novel gene whose mutation could be served as a potential biomarker for prognosis, TMB, and immunotherapy of EAC patients.
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DOI：
10.1002/gcc.22539
发表时间：
2018-07
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Wolff RK;Hoffman MD;Wolff EC;Herrick JS;Sakoda LC;Samowitz WS;Slattery ML
通讯作者：
Slattery ML
影响因子：
3.7
作者：
Hoshida Y;Brunet JP;Tamayo P;Golub TR;Mesirov JP
通讯作者：
Mesirov JP
DOI：
10.1126/science.aaf1490
发表时间：
2016-03-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGranahan N;Furness AJ;Rosenthal R;Ramskov S;Lyngaa R;Saini SK;Jamal-Hanjani M;Wilson GA;Birkbak NJ;Hiley CT;Watkins TB;Shafi S;Murugaesu N;Mitter R;Akarca AU;Linares J;Marafioti T;Henry JY;Van Allen EM;Miao D;Schilling B;Schadendorf D;Garraway LA;Makarov V;Rizvi NA;Snyder A;Hellmann MD;Merghoub T;Wolchok JD;Shukla SA;Wu CJ;Peggs KS;Chan TA;Hadrup SR;Quezada SA;Swanton C
通讯作者：
Swanton C
影响因子：
30.8
作者：
Dulak, Austin M.;Stojanov, Petar;Peng, Shouyong;Lawrence, Michael S.;Fox, Cameron;Stewart, Chip;Bandla, Santhoshi;Imamura, Yu;Schumacher, Steven E.;Shefler, Erica;McKenna, Aaron;Carter, Scott L.;Cibulskis, Kristian;Sivachenko, Andrey;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Auclair, Daniel;Thompson, Kristin;Sougnez, Carrie;Onofrio, Robert C.;Guiducci, Candace;Beroukhim, Rameen;Zhou, Zhongren;Lin, Lin;Lin, Jules;Reddy, Rishindra;Chang, Andrew;Landrenau, Rodney;Pennathur, Arjun;Ogino, Shuji;Luketich, James D.;Golub, Todd R.;Gabriel, Stacey B.;Lander, Eric S.;Beer, David G.;Godfrey, Tony E.;Getz, Gad;Bass, Adam J.
通讯作者：
Bass, Adam J.
影响因子：
16.6
作者：
Yoshihara, Kosuke;Shahmoradgoli, Maria;Martinez, Emmanuel;Vegesna, Rahulsimham;Kim, Hoon;Torres-Garcia, Wandaliz;Trevino, Victor;Shen, Hui;Laird, Peter W.;Levine, Douglas A.;Carter, Scott L.;Getz, Gad;Stemke-Hale, Katherine;Mills, Gordon B.;Verhaak, Roel G. W.
通讯作者：
Verhaak, Roel G. W.