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Association between mutations of critical pathway genes and survival outcomes according to the tumor location in colorectal cancer
Cancer, 2017-09, Vol.123 (18), p.3513-3523
Lee, Dae‐Won
Han, Sae‐Won
Cha, Yongjun
Bae, Jeong Mo
Kim, Hwang‐Phill
Lyu, Jaemyun
Han, Hyojun
Kim, Hyoki
Jang, Hoon
Bang, Duhee
Huh, Iksoo
Park, Taesung
Won, Jae‐Kyung
Jeong, Seung‐Yong
Park, Kyu Joo
Kang, Gyeong Hoon
Kim, Tae‐You
2017
Details
Autor(en) / Beteiligte
Lee, Dae‐Won
Han, Sae‐Won
Cha, Yongjun
Bae, Jeong Mo
Kim, Hwang‐Phill
Lyu, Jaemyun
Han, Hyojun
Kim, Hyoki
Jang, Hoon
Bang, Duhee
Huh, Iksoo
Park, Taesung
Won, Jae‐Kyung
Jeong, Seung‐Yong
Park, Kyu Joo
Kang, Gyeong Hoon
Kim, Tae‐You
Titel
Association between mutations of critical pathway genes and survival outcomes according to the tumor location in colorectal cancer
Ist Teil von
Cancer, 2017-09, Vol.123 (18), p.3513-3523
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
BACKGROUND Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS Targeted next‐generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK‐RAS, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase [PI3K], and transforming growth factor β [TGF‐β]) was performed for 516 patients with stage III or high‐risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse‐free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location. RESULTS The mutation rates for the WNT, P53, RTK‐RAS, PI3K, and TGF‐β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36‐0.99), whereas a mutation in the RTK‐RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01‐2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit α (PIK3CA), and B‐Raf proto‐oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK‐RAS pathway mutation was significant only for distal tumors. CONCLUSIONS A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK‐RAS pathway mutation was associated with worse RFS. The significance of the prognostic impact differed according to the tumor location. Cancer 2017;123:3513‐23. © 2017 American Cancer Society. Targeted next‐generation sequencing of 40 genes has demonstrated that identifying a pathway mutation can predict a patient's prognosis. In addition, the prognostic role of these pathway mutations differs with the tumor location.
Sprache
Englisch
Identifikatoren
ISSN: 0008-543X
eISSN: 1097-0142
DOI: 10.1002/cncr.30760
Titel-ID: cdi_proquest_miscellaneous_1899792171
Format
–
Schlagworte
1-Phosphatidylinositol 3-kinase
,
Adenomatous polyposis coli
,
Adult
,
Aged
,
Cancer
,
cancer genetics
,
Catalysis
,
Chemotherapy
,
Chemotherapy, Adjuvant
,
Class I Phosphatidylinositol 3-Kinases - genetics
,
Cohort Studies
,
Colectomy - methods
,
Colorectal cancer
,
Colorectal carcinoma
,
Colorectal Neoplasms - genetics
,
Colorectal Neoplasms - mortality
,
Colorectal Neoplasms - pathology
,
Colorectal Neoplasms - therapy
,
Combined Modality Therapy
,
Confidence Intervals
,
Critical Pathways
,
Female
,
Gene Expression Regulation, Neoplastic
,
Gene sequencing
,
Genes
,
Genes, ras
,
Homology
,
Humans
,
K-Ras protein
,
Kinases
,
Male
,
Medical prognosis
,
Middle Aged
,
Mutation
,
Mutation rates
,
Neuroblastoma
,
Odds Ratio
,
Oxaliplatin
,
p53 Protein
,
pathway mutation
,
Pathways
,
Patients
,
Phosphatidylinositol 4,5-diphosphate
,
Polyposis coli
,
Predictive Value of Tests
,
Prognosis
,
Protein-serine/threonine kinase
,
Proto-Oncogenes - genetics
,
Raf protein
,
Receptor, Epidermal Growth Factor - genetics
,
Republic of Korea
,
Retrospective Studies
,
Sarcoma
,
Surgery
,
Survival
,
Survival Analysis
,
Threonine
,
Treatment Outcome
,
tumor location
,
Tumors
,
Wnt protein
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