Girdin (GIV) Expression as a Prognostic Marker of Recurrence in Mismatch Repair-Proficient Stage II Colon Cancer
| Autor: | Rodrigo Jover, Zhiming Liao, Matthew Croxford, Rebecca Bowermaster, Song Hu, Jayesh Desai, Bonnie LaFleur, Andrea Muranyi, Ulrich-Peter Rohr, Peter Gibbs, Patrick Brunhoeber, Shalini Singh, Yifei Zhu, Ian T. Jones, Jeanne Tie, Pradipta Ghosh, R. Ridder, Volker Teichgräber, Ben Tran, Ajay Goel, Katherine Leith, Paul Waring, Kandavel Shanmugam |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Colorectal cancer Lymphovascular invasion medicine.medical_treatment Vesicular Transport Proteins DNA Mismatch Repair 0302 clinical medicine Adjuvant Cancer screening and diagnosis Tumor Microfilament Proteins Prognosis Colo-Rectal Cancer Detection Local Chemotherapy Adjuvant 030220 oncology & carcinogenesis Cohort Colonic Neoplasms Immunohistochemistry Female 4.2 Evaluation of markers and technologies medicine.medical_specialty Oncology and Carcinogenesis Disease-Free Survival Article 03 medical and health sciences Breast cancer Internal medicine medicine Biomarkers Tumor Chemotherapy Humans Neoplasm Invasiveness Oncology & Carcinogenesis Aged Neoplasm Staging Gynecology business.industry Microsatellite instability medicine.disease Neoplasm Recurrence 030104 developmental biology Tumor progression Neoplasm Recurrence Local Digestive Diseases business Biomarkers |
| Zdroj: | CLINICAL CANCER RESEARCH r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante instname Clinical cancer research : an official journal of the American Association for Cancer Research, vol 22, iss 14 r-FISABIO. Repositorio Institucional de Producción Científica |
| ISSN: | 1078-0432 |
| Popis: | Purpose: Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. Experimental Design: Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. Results: For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50–9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03–59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24–11.12]. Conclusions: GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms. Clin Cancer Res; 22(14); 3488–98. ©2016 AACR. |
| Databáze: | OpenAIRE |
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