HuR Status Is A Powerful Marker For Prognosis And Response To Chemotherapy For Resected Pancreatic Ductal Adenocarcinoma Patients.
*Nathan G Richards, *Agnes K Witkiewicz, *Christina L Costantino, *Dane R Grenda, *David W Rittenhouse, *Eugene P Kennedy, *Jonathan R Brody, Charles J Yeo
Thomas Jefferson University, Philadelphia, PA
OBJECTIVE(S): Treatment of pancreatic ductal adenocarcinoma (PDA) typically includes chemotherapy with gemcitabine. No reliable biomarker exists for overall prognosis or response to chemotherapy. Two previously proposed prognostic markers, COX-2 and VEGF, are regulated by HuR, an mRNA binding protein that we have demonstrated to be a promising predictive marker of gemcitabine response (Cancer Research 2009, 69:4567-72). This study was designed to evaluate a clinically useful biomarker for PDA.
METHODS: A tissue microarray of specimens including 53 with PDA, who underwent potentially curative resection, was analyzed. HuR, COX-2, and VEGF status were correlated with clinical data and compared for relative utility.
RESULTS: Roughly 50% (27/53) of patients had elevated cytoplasmic HuR expression (HuR+). These patients had worse pathologic features (i.e. positive lymph nodes (75%) and AJCC pathologic stage 2 or greater (94%)) compared to HuR- patients. Cytoplasmic HuR status correlated with staging better than VEGF or COX-2 expression alone. When used in combination, HuR cellular positivity with VEGF+ status yielded 100% lymph node positivity. Additionally, HuR status was an unprecedented positive predictive marker for overall survival in patients treated with gemcitabine pushing median survival over 40 months in the HuR+ patient population (p-value 0.0049).
CONCLUSIONS: HuR status is a robust predictor of outcome for patients with resected PDA. This study supports the notion that HuR should be used by clinicians for the individualized treatment for PDA.