The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma.
The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma.
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原因得分：一种表观遗传学和临床病理评分，可以预测早期口腔鳞状细胞癌患者生存不良的风险。
DOI：
10.1186/s40364-021-00292-x
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发表时间：
2021-06-05
影响因子：
11.1
通讯作者：
Aouizerat BE
中科院分区：
文献类型：
--
作者：
Viet CT;Yu G;Asam K;Thomas CM;Yoon AJ;Wongworawat YC;Haghighiabyaneh M;Kilkuts CA;McGue CM;Couey MA;Callahan NF;Doan C;Walker PC;Nguyen K;Kidd SC;Lee SC;Grandhi A;Cheng AC;Patel AA;Philipone E;Ricks OL;Allen CT;Aouizerat BE
口腔鳞状细胞癌(OSCC)是一种反复无常的癌症，即使在早期患者的生存率也很低。迫切需要开发更精确的风险评估方法，以适当地定制临床治疗。全基因组关联研究还没有产生一个可行的生物标记物。然而，这些研究受到使用异质性队列的限制，尽管口腔鳞癌是一种严重受表观遗传学调控的癌症，但没有关注甲基化，也没有将分子数据与临床病理数据结合起来进行风险预测。在这项研究中，我们专注于早期(I/II)口腔鳞状细胞癌，并创建了一个称为原因评分的风险评分，该评分结合了临床病理特征和12基因甲基化特征，以预测5年死亡的风险。我们结合了来自内部队列(n = 515)和癌症基因组图谱队列(n = 58)的数据。我们收集了两个队列的临床病理数据，以得出原因评分的非分子部分。然后，我们分析了TCGA队列DNA甲基化数据，得出了风险分数的分子部分。内部队列的5年疾病特定生存率为63%，TCGA队列的5年疾病特定生存率为86%。年龄、种族、性别、吸烟、饮酒、组织学分级、分期、神经侵袭(PNI)、淋巴血管侵袭(LVI)和切缘状况是两组队列中预测能力最高的临床病理特征。这个由10个非分子特征组成的小组预测了5年内的死亡风险，协调性(C)指数 = 为0.67。我们的分子图谱由12个基因的甲基化特征(即HORMAD2、MYLK、GPR133、SOX8、TRPA1、ABCA2、HGFAC、MCPH1、WDR86、CACNA1H、RNF216、CCNJL)组成，在存活5 年与死亡5年的患者之间具有最显著的甲基化差异。所有12个基因都已经与其他癌症的存活率有关。在这些基因中，只有SOX8以前与口腔鳞癌有关；我们的研究是第一次将其余11个基因与口腔鳞癌生存联系起来。分子和非分子的组合小组形成了原因得分，该得分预测死亡风险的c指数 = 为0.915。Reason评分是预测早期口腔鳞癌患者死亡风险的一个有前景的生物标志物。在更大的独立队列中验证原因得分是合理的。网上版载有补充材料，可在10.1186/s40364-021-00292-x查阅。
Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality. We combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score. 5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915. The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted. The online version contains supplementary material available at 10.1186/s40364-021-00292-x.
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影响因子：
7.4
作者：
Galon J;Pagès F;Marincola FM;Angell HK;Thurin M;Lugli A;Zlobec I;Berger A;Bifulco C;Botti G;Tatangelo F;Britten CM;Kreiter S;Chouchane L;Delrio P;Arndt H;Asslaber M;Maio M;Masucci GV;Mihm M;Vidal-Vanaclocha F;Allison JP;Gnjatic S;Hakansson L;Huber C;Singh-Jasuja H;Ottensmeier C;Zwierzina H;Laghi L;Grizzi F;Ohashi PS;Shaw PA;Clarke BA;Wouters BG;Kawakami Y;Hazama S;Okuno K;Wang E;O'Donnell-Tormey J;Lagorce C;Pawelec G;Nishimura MI;Hawkins R;Lapointe R;Lundqvist A;Khleif SN;Ogino S;Gibbs P;Waring P;Sato N;Torigoe T;Itoh K;Patel PS;Shukla SN;Palmqvist R;Nagtegaal ID;Wang Y;D'Arrigo C;Kopetz S;Sinicrope FA;Trinchieri G;Gajewski TF;Ascierto PA;Fox BA
通讯作者：
Fox BA
GPR133 (ADGRD1) 是一种粘附 G 蛋白偶联受体，是胶质母细胞瘤生长所必需的。
影响因子：
6.2
作者：
Bayin, N. S.;Frenster, J. D.;Kane, J. R.;Rubenstein, J.;Modrek, A. S.;Baitalmal, R.;Dolgalev, I.;Rudzenski, K.;Scarabottolo, L.;Crespi, D.;Redaelli, L.;Snuderl, M.;Golfinos, J. G.;Doyle, W.;Pacione, D.;Parker, E. C.;Chi, A. S.;Heguy, A.;MacNeil, D. J.;Shohdy, N.;Zagzag, D.;Placantonakis, D. G.
通讯作者：
Placantonakis, D. G.
实体瘤中T型钙通道基因特征的预后相关性：准备临床验证的相关性。
影响因子：
3.7
作者：
Fornaro L;Vivaldi C;Lin D;Xue H;Falcone A;Wang Y;Crea F;Bootman MD
通讯作者：
Bootman MD
影响因子：
4.6
作者：
Kim, Yi-Jun;Kim, Jin Ho
通讯作者：
Kim, Jin Ho
影响因子：
7.4
作者：
Gu, Xiang;Wang, Bingzhi;Sun, Lu-Zhe
通讯作者：
Sun, Lu-Zhe