Sonic Hedgehog and Gli1 expression predict outcome in resected pancreatic adenocarcinoma
Menée à partir d'échantillons tumoraux prélevés sur 567 patients atteints d'un adénocarcinome canalaire du pancréas traité par chirurgie, cette étude met en évidence une association entre l'expression tumorale des protéines "Sonic Hedgehog" et "Gli1" et la survie des patients
Purpose : Aberrant activation of the hedgehog (Hh) pathway is implicated in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis. We investigated the prognostic and predictive value of four Hh signaling proteins and of the tumor stromal density.
Experimental Design : Using tissue microarray and immunohistochemistry, the expression of Shh, Gli1, SMO and PTCH1 were assessed in 567 patients from three independent cohorts who underwent surgical resection for PDAC. In 82 patients, the tumor stromal index (SI) was calculated and its association with overall survival (OS) and disease-free survival (DFS) was investigated.
Results : Shh and Gli1 protein abundance were independent prognostic factors in resected PDACs; low expressors for those proteins experiencing a better OS and DFS. The combination of Shh and Gli1 levels was the most significant predictor for OS and defined 3 clinically relevant subgroups of patients with different prognosis (Gli1 and Shh low; HR set at 1 v 3.08 for Shh or Gli1 high v 5.69 for Shh and Gli1 high; P< 0.001). The two validating cohorts recapitulated the findings of the training cohort. After further stratification by lymph node status, the prognostic significance of combined Shh and Gli1 was maintained. The tumor SI was correlated with Shh levels and was significantly associated with OS (p = 0.023).
Conclusions : Shh and Gli1 are prognostic biomarkers for patients with resected PDAC.
Clinical Cancer Research , résumé, 2014