研究动态
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细胞减灭手术和腹腔热化疗患者的结直肠起源的基因簇:KRAS 而不是 TP53 簇改变与不良结果相关。

Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

发表日期:2024 Jul 13
作者: Allen T Yu, David N Hanna, Thomas M Li, Elad Sarfaty, Nazanin Khajoueinejad, Judy Li, Benjamin Golas, Spiros Hiotis, Daniel Labow, Umut Sarpel, Deepa R Magge, Noah A Cohen
来源: ANNALS OF SURGICAL ONCOLOGY

摘要:

基因突变对接受结直肠癌 (CRC) 细胞减灭术 (CRS) 联合腹腔热腹腔化疗 (HIPEC) 的患者的预后影响尚不明确。我们旨在以无人监督的方式描述基因分类,以及这种方法的结果对接受 CRS-HIPEC 的患者进行了一项回顾性、双机构研究,并获得了靶向突变数据,中位随访时间为 61 个月。使用 STRING v11.5 进行功能链接分析。使用无监督 k 均值聚类对具有相似功能意义的基因进行聚类。采用卡方、Kaplan-Meier、log-rank检验进行比较统计。2007年至2022年期间,64例CRC起源的腹膜癌患者接受了CRS-HIPEC,并提取了基因突变数据。我们确定了 19 个独特的改变基因,其中 KRAS (56%)、TP53 (33%) 和 APC (22%) 是最常见的改变; 12.5% 的人同时改变了 KRAS/TP53。创建交互组图后,k 均值聚类揭示了三个功能簇。对三个簇的 Reactome Pathway 分析显示了独特的途径 (1):Ras/FGFR3 信号传导; (2)p53信号传导; (3):NOTCH信令。第 1 组中 71% 的患者存在 KRAS 突变,中位总生存期为 52.3 个月 (p < 0.05)。接受 CRS-HIPEC 治疗的 CRC 来源的腹膜癌病 (PC) 患者,且肿瘤携带第 1 组中的突变(Ras/FGFR3 信号传导)结果更差。对于 CRC 起源的 PC 患者,通路破坏和以集群为中心的视角可能比个体基因改变对预后的影响更大。© 2024。外科肿瘤学会。
The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined.We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population.A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics.Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05).Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.© 2024. Society of Surgical Oncology.