Correction: Genetic Diversity of the KIR/HLA System and Outcome of Patients with Metastatic Colorectal Cancer Treated with Chemotherapy

نویسندگان

  • Valli De Re
  • Laura Caggiari
  • Mariangela De Zorzi
  • Renato Talamini
  • Vito Racanelli
  • Mario D’ Andrea
  • Angela Buonadonna
  • Vittorina Zagonel
  • Erika Cecchin
  • Federico Innocenti
  • Giuseppe Toffoli
چکیده

OBJECTIVE To explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI). METHODS A total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based upon the gene content and variants. Genetic associations with complete response (CR), time to progression (TTP) and overall survival (OS) were evaluated by calculating odds and hazard ratios. Multivariate modeling with prognostic covariates was also performed. RESULTS For CR, the presence of KIR2DL5A, 2DS5, 2DS1, 3DS1, and KIR3DS1/HLA-Bw4-I80 was associated with increased CR rates, with median ORs ranging from 2.1 to 4.3, while the absence of KIR2DS4 and 3DL1 was associated with increased CR rates (OR 3.1). After univariate analysis, patients that underwent resective surgery of tumor, absence of KIR2DS5, and presence of KIR3DL1/HLA-Bw4-I80 showed a significant better OS (HR 1.5 to 2.8). Multivariate analysis identified as parameters independently related to OS the type of treatment (surgery; HR 2.0) and KIR3DL1/HLA-Bw4-I80 genotype (HR for T-I80 2.7 and for no functional KIR/HLA interaction 1.8). For TTP, no association with KIR/HLA genes was observed. CONCLUSION This study, for the first time, evidences that the genotyping for KIR-HLA pairs are found predictive markers associated with complete response and improves overall survival prediction of FOLFIRI treatment response in metastatic colorectal cancer. These results suggest a role of the KIR/HLA system in patient outcome, and guide new research on the immunogenetics of mCRC through mechanistic studies and clinical validation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Correction: Genetic Diversity of the KIR/HLA System and Outcome of Patients with Metastatic Colorectal Cancer Treated with Chemotherapy

There are errors in some of the authors’ affiliations. Please refer to the correct affiliations below: Dr. Laura Caggiari, Dr. Mariangela De Zorzi and De Re Valli: Bio-Proteomics Core Facility, Experimental and Clinical Pharmacology, Department of Translational Research (molecular oncology, advanced diagnostics and cell therapies) Dr Toffoli Giuseppe and Dr. Erika Cecchin: Experimental and Clin...

متن کامل

HLA-KIR Interactions and Immunity to Viral Infections

Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptors (KIRs), and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic di...

متن کامل

“How should we treat older patients with Metastatic Colorectal Cancer, A Review”

Nearly 50 % of newly diagnosed colorectal cancer, affect people over 70 years of age. Inclusion of older patients in clinical trials has been extremely rare. As a result, there is debate on how to manage these patients because it is still unclear how to balance the therapeutic advantages and toxicities. For patients who do not have comorbid conditions, with performance status (P.S.) 0–1, treatm...

متن کامل

بهبود بقا بیماران مبتلا به لوسمی لنفوبلاستیک حاد فاقد HLA-A3/11 برای KIR3DL2 دهنده پس از پیوند سلول های بنیادی خونساز از خواهر یا برادر با HLA مشابه بدون تخلیه سلول T

A potential factor influencing hematopoietic stem cells transplantation (HSCT) outcome is the presence of donor-derived alloreactive natural killer (NK) cells. This retrospective analysis studied the impact of NK alloreactivity based on the missing KIR ligand, for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) patients undergoing non-T-cell depleted HLA-identical sibling HS...

متن کامل

ارزیابی فراوانی جهش‌های ژن KRAS در بیماران ایرانی مبتلا به سرطان کولورکتال

Background: Kirsten rat sarcoma (KRAS) gene is a target of genetic alterations which are diagnostic and prognostic biomarkers in patients with metastatic colorectal cancer who are treated with monoclonal anti-EGFR antibodies such as cetuximab and panitumumab. KRAS mutations are seen in 35-42% of patients with colorectal cancer. The high frequency of these mutations in colorectal cancer represen...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014