Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer

Abstract

Background:Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins: Growth Hormone-Releasing Hormone Receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL in specimens of locally advanced rectal cancer patients and time to metastasis as well as 10-year Overall Survival (OS). We also investigated whether these outcome measures were associated with the presence of other clinical parameters.Methods: 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers, clinical parameters, time-to metastasis and 10-year OS.Results: High levels of p-Akt, GHRH-R and Hsp90 were associated with significantly decreased 10-year OS (p = 0.001; p = 0.000; p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both significantly longer time to metastasis and improved 10-year OS. Conclusion:Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of 10year OS in locally advanced rectal cancer patients. GHRH-R and Hsp90 expression were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for anticancer treatment of advanced rectal cancer.