Lahoz Sara, Rodríguez Adela, Fernández Laia, Gorría Teresa, Moreno Reinaldo, Esposito Francis, Oliveres Helena, Albiol Santiago, Saurí Tamara, Pesantez David, Riu Gisela, Cuatrecasas Miriam, Jares Pedro, Pedrosa Leire, Pineda Estela, Postigo Antonio, Castells Antoni, Prat Aleix, Maurel Joan, Camps Jordi
Gastrointestinal and Pancreatic Oncology Team, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic of Barcelona, Consorcio de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, 08036 Barcelona, Spain.
Translational Genomics and Targeted Therapeutics in Solid Tumors Group, Medical Oncology Department, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
Cancers (Basel). 2022 Nov 30;14(23):5921. doi: 10.3390/cancers14235921.
Next-generation sequencing (NGS) provides a molecular rationale to inform prognostic stratification and to guide personalized treatment in cancer patients. Here, we determined the prognostic and predictive value of actionable mutated genes in metastatic colorectal cancer (mCRC). Among a total of 294 mCRC tumors examined by targeted NGS, 200 of them derived from patients treated with first-line chemotherapy plus/minus monoclonal antibodies were included in prognostic analyses. Discriminative performance was assessed by time-dependent estimates of the area under the curve (AUC). The most recurrently mutated genes were (64%), or (49%), (15%), (14%), (13%), and (9.5%). Mutations in correlated with worse OS rates ( = 0.036; HR, 2.24) independently of clinical factors. Concurrent mutations in and were associated with increased risk of death ( = 0.02; HR, 3.31) as well as double-mutated and ( = 0.03; HR, 2.91). Analysis of the MSK-IMPACT mCRC cohort (N = 1095 patients) confirmed the same prognostic trend for the previously identified mutated genes. Addition of the mutational status of these genes upon clinical factors resulted in a time-dependent AUC of 87%. Gene set enrichment analysis revealed specific molecular pathways associated with and mutations in -defficient tumors. Conclusively, and mutations in -altered tumors were predictive of a negative prognostic outcome in mCRC patients treated with first-line regimens.
下一代测序（NGS）为癌症患者的预后分层提供了分子依据，并指导个性化治疗。在此，我们确定了转移性结直肠癌（mCRC）中可操作突变基因的预后和预测价值。在通过靶向NGS检测的总共294例mCRC肿瘤中，其中200例来自接受一线化疗加/减单克隆抗体治疗的患者，纳入预后分析。通过曲线下面积（AUC）的时间依赖性估计来评估判别性能。最常发生突变的基因是（64%）、或（49%）、（15%）、（14%）、（13%）和（9.5%）。独立于临床因素，中的突变与较差的总生存率相关（=0.036；HR，2.24）。和同时发生的突变与死亡风险增加相关（=0.02；HR，3.31），以及和双突变（=0.03；HR，2.91）。对MSK-IMPACT mCRC队列（N = 1095例患者）的分析证实了先前鉴定的突变基因具有相同的预后趋势。将这些基因的突变状态加入临床因素后，时间依赖性AUC为87%。基因集富集分析揭示了与缺陷肿瘤中及突变相关的特定分子途径。总之，在改变的肿瘤中的和突变可预测接受一线治疗方案的mCRC患者的不良预后结果。
