Oya Orun1, Sevgi Özden2, Olca Kılınç3, Pınar Mega Tiber3, Pelin Yonar3, Zerrin Özgen4, Hazan Özyurt2. 1. Department of Biophysics, School of Medicine, Marmara University, Maltepe Basibuyuk Yolu Sok. 9/1, Maltepe, 34854, Istanbul, Turkey. oyaorun@yahoo.com. 2. Clinic of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey. 3. Department of Biophysics, School of Medicine, Marmara University, Maltepe Basibuyuk Yolu Sok. 9/1, Maltepe, 34854, Istanbul, Turkey. 4. Department of Radiation Oncology, School of Medicine, Marmara University, Istanbul, Turkey.
Abstract
BACKGROUND: Preoperative chemoradiotherapy has long been accepted as a method to improve survival and lifetime quality of rectal cancer patients. However, physiologic effects of these therapies largely depend on the resistance of cells to the radiation, type of chemotherapeutic agents and individual responses. As one of the signaling cascades involved in chemo- or radiation- resistance, the present study focused on several proteins involved in pTEN/Akt/mTOR pathway to explore their prognostic significance. MATERIALS AND METHODS: Samples from advanced stage rectal cancer patients were analyzed to detect expression levels of pTEN/Akt/mTOR pathway related proteins pTEN, mLST8, REDD1, BNIP3, SAG and NOXA, together with p53, by RT-qPCR. Kaplan-Meier analysis was used to assess expression-survival relation and correlations among all proteins and clinicopathological features were statistically analyzed. RESULTS: Except p53, none of the proteins showed prognostic significance. High p53 expression presented clear impact on overall survival and disease free survival. It was also significantly related to pathologic complete response. p53 showed high correlation to local recurrence as well. On the other hand, strong correlation was observed with PTEN expression and tumor response, but not with survival. High associations were also observed between mLST8/REDD1, PTEN and NOXA, confirming their role in the same cascade. CONCLUSION: The contentious role of p53 as a prognostic biomarker in colorectal cancer was further affirmed, while PTEN and REDD1 could be suggested as potential candidates. Additionally, NOXA emerges as a conjunctive element for different signaling pathways.
BACKGROUND: Preoperative chemoradiotherapy has long been accepted as a method to improve survival and lifetime quality of rectal cancer patients. However, physiologic effects of these therapies largely depend on the resistance of cells to the radiation, type of chemotherapeutic agents and individual responses. As one of the signaling cascades involved in chemo- or radiation- resistance, the present study focused on several proteins involved in pTEN/Akt/mTOR pathway to explore their prognostic significance. MATERIALS AND METHODS: Samples from advanced stage rectal cancer patients were analyzed to detect expression levels of pTEN/Akt/mTOR pathway related proteins pTEN, mLST8, REDD1, BNIP3, SAG and NOXA, together with p53, by RT-qPCR. Kaplan-Meier analysis was used to assess expression-survival relation and correlations among all proteins and clinicopathological features were statistically analyzed. RESULTS: Except p53, none of the proteins showed prognostic significance. High p53 expression presented clear impact on overall survival and disease free survival. It was also significantly related to pathologic complete response. p53 showed high correlation to local recurrence as well. On the other hand, strong correlation was observed with PTEN expression and tumor response, but not with survival. High associations were also observed between mLST8/REDD1, PTEN and NOXA, confirming their role in the same cascade. CONCLUSION: The contentious role of p53 as a prognostic biomarker in colorectal cancer was further affirmed, while PTEN and REDD1 could be suggested as potential candidates. Additionally, NOXA emerges as a conjunctive element for different signaling pathways.
Authors: Sevgi A Ozden; Hazan Ozyurt; Zerrin Ozgen; Olca Kilinc; Mustafa Oncel; Aylin E Gul; Nimet Karadayi; Nedime Serakinci; Beki Kan; Oya Orun Journal: World J Gastroenterol Date: 2011-11-28 Impact factor: 5.742