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

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dc.contributor.authorLee, Dae-Won-
dc.contributor.authorHan, Sae-Won-
dc.contributor.authorCha, Yongjun-
dc.contributor.authorBae, Jeong Mo-
dc.contributor.authorKim, Hwang-Phill-
dc.contributor.authorLyu, Jaemyun-
dc.contributor.authorHan, Hyojun-
dc.contributor.authorKim, Hyoki-
dc.contributor.authorJang, Hoon-
dc.contributor.authorBang, Duhee-
dc.contributor.authorWon, Jae-Kyung-
dc.contributor.authorJeong, Seung-Yong-
dc.contributor.authorPark, Kyu Joo-
dc.contributor.authorKang, Gyeong Hoon-
dc.contributor.authorKim, Tae-You-
dc.date.accessioned2019-06-12T08:21:46Z-
dc.date.available2019-06-12T17:25:06Z-
dc.date.issued2019-05-06-
dc.identifier.citationBMC Cancer. 19(1):421ko_KR
dc.identifier.issn1471-2407-
dc.identifier.urihttps://hdl.handle.net/10371/153912-
dc.description.abstractBackground
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.
ko_KR
dc.description.sponsorshipThis research was supported by the Seoul National University Hospital (SNUH) Research Fund (03–2014-0440) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277 and HI13C2163). The funding bodies had no influence on the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.ko_KR
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectColorectal cancerko_KR
dc.subjectTGF-β pathwayko_KR
dc.subjectMucinous adenocarcinomako_KR
dc.subjectSurvival after recurrenceko_KR
dc.titleAssociation of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapyko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor이대원-
dc.contributor.AlternativeAuthor한새원-
dc.contributor.AlternativeAuthor차용준-
dc.contributor.AlternativeAuthor배정모-
dc.contributor.AlternativeAuthor김황필-
dc.contributor.AlternativeAuthor류재문-
dc.contributor.AlternativeAuthor한효준-
dc.contributor.AlternativeAuthor김효기-
dc.contributor.AlternativeAuthor장훈-
dc.contributor.AlternativeAuthor방두희-
dc.contributor.AlternativeAuthor원재경-
dc.contributor.AlternativeAuthor정승용-
dc.contributor.AlternativeAuthor박규주-
dc.contributor.AlternativeAuthor강경훈-
dc.contributor.AlternativeAuthor김태-
dc.identifier.doi10.1186/s12885-019-5650-0-
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2019-05-12T20:36:15Z-
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