Girdin (GIV) expression as a prognostic marker of recurrence in mismatch repair proficient stage II colon cancer

Ghosh, P; Tie, J; Muranyi, A; Singh, S; Brunhoeber, P; Leith, K; Bowermaster, R; Liao, Z; Zhu, Y; LaFleur, B; Tran, B; Desai, J; Jones, IT; Croxford, M; Jover, R; Goel, A; Waring, P; Hu, S; Teichgraeber, V; Rohr, UP; Ridder, R; Shanmugam, K; Gibbs, P

Author(s): Ghosh, P; Tie, J; Muranyi, A; Singh, S; Brunhoeber, P; Leith, K; Bowermaster, R; Liao, Z; Zhu, Y; LaFleur, B; Tran, B; Desai, J; Jones, IT; Croxford, M; Jover, R; Goel, A; Waring, P; Hu, S; Teichgraeber, V; Rohr, UP; Ridder, R; Shanmugam, K; Gibbs, P;
Details: Publication Year 2016-03-30,Volume 22,Issue #14,Page 3488-98
Journal Title: Clinical Cancer Research
Publication Type: Journal Article
Abstract: PURPOSE: Prognostic markers that identify patients with stage II colon cancers (CC) who are at 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 immunohistochemistry (IHC) using a newly developed monoclonal antibody together with a mismatch repair (MMR)-specific antibody panel in three stage II CC patient cohorts, ie. 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% versus 84.8%; HR:3.74, 95%CI: 1.50-9.32; Test: 85.9% versus 97.9%, HR:7.83, 95%CI:1.03-59.54; Validation: 59.4% versus 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 CC. 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.
Publisher: AACR
Research Division(s): Systems Biology And Personalised Medicine
PubMed ID: 27029492
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-15-2290
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2016-04-05 01:43:56

Last Modified: 2020-04-07 02:34:27