Genome-Wide Scan for Copy Number Alteration Association with Relapse-Free Survival in Colorectal Cancer with Liver Metastasis Patients
Journal
Journal of clinical medicine
Journal Volume
7
Journal Issue
11
Date Issued
2018-11-18
Author(s)
Yang, Po-Sheng
Hsu, Hsi-Hsien
Hsu, Tzu-Chi
Chen, Ming-Jen
Wang, Cin-Di
Hsu, Yi-Chiung
Li, Ker-Chau
Abstract
Predicting a patient's risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes-S100PBP, CSMD2, TGFBI-significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.
Subjects
biomarker; colorectal cancer liver metastases; copy number alteration; gene signature; relapse-free survival
Biomarker; Colorectal cancer liver metastases; Copy number alteration; Gene signature; Relapse-free survival
SDGs
Other Subjects
adult; agar gel electrophoresis; aged; Article; cancer staging; clinical article; clinical outcome; cohort analysis; colorectal cancer; comparative genomic hybridization; computer model; copy number variation; CSMD2 gene; DNA fragmentation assay; female; follow up; gene; gene dosage; genetic analysis; genome-wide association study; human; human tissue; liver metastasis; liver resection; male; observational study; recurrence free survival; S100PBP gene; survival analysis; TGFBI gene; tumor volume; validation study; very elderly; whole genome sequencing
Type
journal article