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

Pradipta Ghosh, Jeanne Tie, Andrea Muranyi, Shalini Singh, Patrick Brunhoeber, Katherine Leith, Rebecca Bowermaster, Zhiming Liao, Yifei Zhu, Bonnie LaFleur, Ben Tran, Jayesh Desai, Ian Jones, Matthew Croxford, Rodrigo Jover, Ajay Goel, Paul Waring, Song Hu, Volker Teichgraber, Ulrich Peter RohrRuediger Ridder, Kandavel Shanmugam, Peter Gibbs

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3488-3498
Number of pages11
JournalClinical Cancer Research
Volume22
Issue number14
DOIs
StatePublished - Jul 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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