Sistema gastrointestinal y digestivo

Abstracto

IGF-2 Growth Factor Expression in Human Rectal Adenocarcinoma

David Weber, Daniel Gödde, Jan Postberg, Hubert Zirngibl, Christian Prinz

Background and objective: The study determined growth factor gene expression obtained from patients undergoing curative total mesorectal excision (TME) between 2009 and 2016 at the Helios Klinikum Wuppertal; Germany (total of n=44). Methods: Rectal cancers were grouped according to Lauren’s classification (UICC I-IV stages); overall survival (OS) and progression free survival (PFS). 25 patients were in UICC III/IV stages, while 19 patients were in UICC I/II stages. VEGF-A/B/C/D, PDGF-A, EGF, IGF-1/2, and corresponding receptor subtypes 1/2 mRNA enrichment was determined using quantitative real-time PCR. Data were correlated to clinical outcome. Results: The obtained results show that VEGF-B and IGF-2 mRNA were significantly higher expressed in rectal adenocarcinoma than adjacent normal tissues, while other GF genes were not significantly affected. IGF-2 levels were further upregulated in advanced stages UICC III/IV where patients received radiotherapy. Patients with good response to neoadjuvant radiotherapy (as determined by the histological Dworak regression score) had significant better overall survival. Expression of microRNA miR-483 (a known microRNA molecule previously associated with IGF-2 expression) was evaluated by TaqMAN PCR, but no significant correlation to IGF-2 levels was detected. Conclusions: IGF-2 appears as a biomarker of rectal adenocarcinoma, but does not serve as predictive parameter for tumor progression or survival. The results encourage further development of biomarkers targeting IGF-2 molecules in blood or urine. Furthermore, IGF-2 levels are increased in patients undergoing radiotherapy and thus, IGF related molecules might also serve as predictors for response to neoadjuvant therapy in rectal adenocarcinoma.