Format

Send to

Choose Destination
BMC Cancer. 2019 May 6;19(1):421. doi: 10.1186/s12885-019-5650-0.

Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy.

Author information

1
Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-Ro, Jongno-Gu, Seoul, 110-744, South Korea.
2
Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-Ro, Jongno-Gu, Seoul, 110-744, South Korea. saewon1@snu.ac.kr.
3
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. saewon1@snu.ac.kr.
4
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
5
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
6
Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.
7
Celemics Inc, Seoul, South Korea.
8
Department of Chemistry College of Science, Yonsei University, Seoul, South Korea.
9
Department of Surgery, Seoul National University Hospital, Seoul, South Korea.

Abstract

BACKGROUND:

Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR.

METHODS:

Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-β, and PI3K).

RESULTS:

Mutation of genes within the WNT, P53, RTK-RAS, TGF-β, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-β pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-β pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-β pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-β pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation.

CONCLUSIONS:

Mutation in genes within TGF-β pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.

KEYWORDS:

Colorectal cancer; Mucinous adenocarcinoma; Survival after recurrence; TGF-β pathway

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center