Tanenbaum Daniel G, Hall William A, Colbert Lauren E, Bastien Amanda J, Brat Daniel J, Kong Jun, Kim Sungjin, Dwivedi Bhakti, Kowalski Jeanne, Landry Jerome C, Yu David S
1 Department of Radiation Oncology, 2 Winship Cancer Institute, Emory University, GA, USA ; 3 Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA ; 4 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA ; 5 Department of Pathology and Laboratory Medicine, 6 Department of Biomedical Informatics, 7 Department of Biostatistics and Bioinformatics, 8 Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Gastrointest Oncol. 2016 Jun;7(3):306-14. doi: 10.21037/jgo.2015.11.04.
BACKGROUND: Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). METHODS: Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. RESULTS: TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13-10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42-42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). CONCLUSIONS: TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma.
背景：结直肠癌（CRC）患者远处转移疾病的基因标志物尚未明确界定。识别与转移性CRC相关的基因改变有助于指导全身和局部治疗策略。我们使用癌症基因组图谱（TCGA）评估了肿瘤坏死因子受体超家族成员10C（TNFRSF10C）拷贝数变异（CNV）与CRC患者远处转移疾病的相关性。 方法：从TCGA获取所有可用CRC患者的基因测序数据和临床特征。有515例具有CNV和临床结局数据的CRC患者样本，包括144例直肠腺癌患者样本的子集。使用TCGA CRC数据集，评估TNFRSF10C的CNV与远处转移疾病（M1对M0）的相关性。进行多因素逻辑回归分析，使用比值比（OR）并采用95%置信区间（CI），对年龄、T分期、N分期、辅助化疗、性别、微卫星不稳定性（MSI）、位置和手术切缘状态进行校正。 结果：CRC患者的TNFRSF10C CNV与远处转移疾病相关[OR 4.81（95%CI，2.13 - 10.85），P<0.001]以及阳性淋巴结相关[OR 18.83（95%CI，8.42 - 42.09）；P<0.001]，但与MSI无关（OR P = 0.799）。在多因素分析中，校正病理T分期、N分期、辅助化疗、性别和MSI后，TNFRSF10C CNV仍与远处转移疾病显著相关（OR P = 0.018）。亚组分析显示，TNFRSF10C CNV在直肠腺癌患者中也与远处转移疾病显著相关（OR P = 0.016）。 结论：CRC患者的TNFRSF10C CNV与远处转移疾病相关。经过进一步验证，此类基因图谱可在临床上用于支持CRC患者的最佳全身治疗策略，而非更积极的局部治疗，包括直肠腺癌放疗。
J Gastrointest Oncol. 2016-6
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