1. Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.
- Author
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Yu AT, Hanna DN, Li TM, Sarfaty E, Khajoueinejad N, Li J, Golas B, Hiotis S, Labow D, Sarpel U, Magge DR, and Cohen NA
- Subjects
- Humans, Female, Male, Retrospective Studies, Middle Aged, Prognosis, Survival Rate, Combined Modality Therapy, Follow-Up Studies, Aged, Biomarkers, Tumor genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Adult, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Colorectal Neoplasms therapy, Hyperthermic Intraperitoneal Chemotherapy, Cytoreduction Surgical Procedures, Proto-Oncogene Proteins p21(ras) genetics, Tumor Suppressor Protein p53 genetics, Peritoneal Neoplasms therapy, Peritoneal Neoplasms secondary, Peritoneal Neoplasms genetics, Mutation
- Abstract
Background: 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., Objective: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population., Methods: 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., Results: 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)., Conclusions: 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.)
- Published
- 2024
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