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

Dae Won Lee, Sae Won Han, Yongjun Cha, Jeong Mo Bae, Hwang Phill Kim, Jaemyun Lyu, Hyojun Han, Hyoki Kim, Hoon Jang, Duhee Bang, Jae Kyung Won, Seung Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae You Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number421
JournalBMC cancer
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 May 6

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oxaliplatin
Colorectal Neoplasms
Recurrence
Drug Therapy
Mutation
Survival
Mucinous Adenocarcinoma
Critical Pathways
Phosphatidylinositol 3-Kinases
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Lee, Dae Won ; Han, Sae Won ; Cha, Yongjun ; Bae, Jeong Mo ; Kim, Hwang Phill ; Lyu, Jaemyun ; Han, Hyojun ; Kim, Hyoki ; Jang, Hoon ; Bang, Duhee ; Won, Jae Kyung ; Jeong, Seung Yong ; Park, Kyu Joo ; Kang, Gyeong Hoon ; Kim, Tae You. / Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy. In: BMC cancer. 2019 ; Vol. 19, No. 1.
@article{14f1bc559a7f45abaa4d93f5a0a0c82e,
title = "Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy",
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.",
author = "Lee, {Dae Won} and Han, {Sae Won} and Yongjun Cha and Bae, {Jeong Mo} and Kim, {Hwang Phill} and Jaemyun Lyu and Hyojun Han and Hyoki Kim and Hoon Jang and Duhee Bang and Won, {Jae Kyung} and Jeong, {Seung Yong} and Park, {Kyu Joo} and Kang, {Gyeong Hoon} and Kim, {Tae You}",
year = "2019",
month = "5",
day = "6",
doi = "10.1186/s12885-019-5650-0",
language = "English",
volume = "19",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

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Lee, DW, Han, SW, Cha, Y, Bae, JM, Kim, HP, Lyu, J, Han, H, Kim, H, Jang, H, Bang, D, Won, JK, Jeong, SY, Park, KJ, Kang, GH & Kim, TY 2019, 'Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy', BMC cancer, vol. 19, no. 1, 421. https://doi.org/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. / Lee, Dae Won; Han, Sae Won; Cha, Yongjun; Bae, Jeong Mo; Kim, Hwang Phill; Lyu, Jaemyun; Han, Hyojun; Kim, Hyoki; Jang, Hoon; Bang, Duhee; Won, Jae Kyung; Jeong, Seung Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae You.

In: BMC cancer, Vol. 19, No. 1, 421, 06.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy

AU - Lee, Dae Won

AU - Han, Sae Won

AU - Cha, Yongjun

AU - Bae, Jeong Mo

AU - Kim, Hwang Phill

AU - Lyu, Jaemyun

AU - Han, Hyojun

AU - Kim, Hyoki

AU - Jang, Hoon

AU - Bang, Duhee

AU - Won, Jae Kyung

AU - Jeong, Seung Yong

AU - Park, Kyu Joo

AU - Kang, Gyeong Hoon

AU - Kim, Tae You

PY - 2019/5/6

Y1 - 2019/5/6

N2 - 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.

AB - 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.

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U2 - 10.1186/s12885-019-5650-0

DO - 10.1186/s12885-019-5650-0

M3 - Article

C2 - 31060539

AN - SCOPUS:85065640189

VL - 19

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JF - BMC Cancer

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