Impact of "killer immunoglobulin-like receptor/ligand" genotypes on outcome following surgery among patients with colorectal cancer: activating KIRS are associated with long-term disease free survival

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dc.contributor.authorDalva, Klara
dc.contributor.authorBeksaç, Meral
dc.contributor.departmentKök Hücre Enstitüsütr_TR
dc.contributor.departmentTıp Fakültesitr_TR
dc.date.accessioned2019-07-01T12:09:04Z
dc.date.available2019-07-01T12:09:04Z
dc.date.issued2015
dc.description.abstractApproximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI =0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/one/two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.tr_TR
dc.description.indexWos
dc.description.indexwos
dc.identifier.issue7tr_TR
dc.identifier.other10.1371/journal.pone.0132526
dc.identifier.startpage01tr_TR
dc.identifier.urihttp://hdl.handle.net/20.500.12575/67080
dc.identifier.volume10tr_TR
dc.language.isoentr_TR
dc.relation.indexWostr_TR
dc.relation.journalPlos Onetr_TR
dc.subjectColontr_TR
dc.subjectTumorstr_TR
dc.subjectRelapsetr_TR
dc.subjectMhc Class-Itr_TR
dc.subjectGenestr_TR
dc.titleImpact of "killer immunoglobulin-like receptor/ligand" genotypes on outcome following surgery among patients with colorectal cancer: activating KIRS are associated with long-term disease free survivaltr_TR
dc.typeArticletr_TR

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