Abstract B56: Potential biomarkers for personalized oncology radiation in uterine cervical cancer
Authors: Pablo Moreno-Acosta, Schyrly Carrillo, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Diana Mayorga, Mónica Molano, Martha Cotes, Nicolas Magne
Journal: Clinical Cancer Research (2018)

Abstract Uterine cervical cancer (UCC) is one of the most prevalent malignant neoplasms in the world. UCC develops beyond the stage in situ and is frequently treated by a combination of intracavitary radiation therapy and external beam radiation therapy; 30-40% of patients with similar prognosis factors do not respond equally to a comparable standard treatment. Therefore, the study and identification of prognostic biomarkers, which indicate the probable course of the disease in an untreated individual, and predictive biomarkers, which allow identification of subpopulations of patients most likely to respond to a given therapy, would be extremely useful in the selection of patients for the development of innovative and effective therapies for locally advanced, metastatic, and refractory uterine cervical cancer. Within work that we have been developing, we reported that gene expression of IGF1R is a strong predictive marker for lack of response to radiotherapy (p=0.018, 95% CI (1.7-41.2)), and patients HPV16 (+) have 28.6 times higher risk of failure treatment; consequently, with the present study, we proposed to determine whether expression of IGF-IR, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, HKII, and clinic-pathologic parameters can be used as prognostic and predictive biomarkers and as possible molecular targets for individualized treatment. Patients and Methods: This prospective cohort study included 149 patients with squamous cell carcinomas of the uterine cervix in FIGO stages IIB (n= 53) and IIIB (n=96). Of the 149 patients, 61 were treated with radiotherapy and 88 with concurrent radio-chemotherapy. Expression of the proteins CAIX, GLUT-1, HIF1α, HKII, IGF-IRα, IGF-IRβ, and Survivin was determined by immunohistochemistry in biopsies taken before treatment. Results: An overexpression was found for GAPDH (100%), followed by Survivin (87%), IGF-IRα (76.5%), IGF-IRβ (74.5%), HIF1α (74.1%), and IGF-IRα and IGF-IRβ (73%); strong expression was observed with low frequency for GLUT-1 (31.1%), CAIX (16.2%), and HKII (10.6%). Hgb level was significantly correlated with treatment response (p=0.01). With a median follow-up of 2.1 years, OS was decreased for patients overexpressing IGF-1R β (p=0.04). The OS of the subgroup of patients with anemia (Hgb &amp;lt; 11 g/dL) and concomitantly overexpressing IGF-1R and GLUT-1 was significantly decreased compared to the opposite control group (p=0.015). Conclusions: The expression of GLUT-1, IGF-1R, and Hgb (≤ 11 g/dl) is associated with poor prognosis, and thus appear to be interesting biomarkers of radiation resistance. In order to contribute to appropriate therapeutic management as a personalized neoadjuvant treatment, a prospective phase II study should be designed in the near future to evaluate the effect of turmeric (curcumin) as an inhibitor of IGF-1Rβ and GLUT1. Note: This abstract was not presented at the conference. Citation Format: Pablo Moreno-Acosta, Schyrly Carrillo, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Diana Mayorga, Mónica Molano, Martha Cotes, Nicolas Magne. Potential biomarkers for personalized oncology radiation in uterine cervical cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B56.