Department of Biophysics, School of Medicine, Marmara University, Maltepe Basibuyuk Yolu Sok. 9/1, Maltepe, 34854, Istanbul, Turkey.
Clinic of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey.
Mol Biol Rep. 2022 Sep;49(9):8461-8472. doi: 10.1007/s11033-022-07665-x. Epub 2022 Jun 21.
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.
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.
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.
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.
术前放化疗长期以来被认为是提高直肠癌患者生存和生活质量的一种方法。然而，这些治疗的生理效应在很大程度上取决于细胞对辐射的抵抗力、化疗药物的类型和个体反应。作为涉及化疗或放疗耐药性的信号通路之一，本研究集中研究了参与 pTEN/Akt/mTOR 通路的几种蛋白质，以探索它们的预后意义。
分析晚期直肠癌患者的样本，通过 RT-qPCR 检测 pTEN/Akt/mTOR 通路相关蛋白 pTEN、mLST8、REDD1、BNIP3、SAG 和 NOXA 以及 p53 的表达水平。采用 Kaplan-Meier 分析评估表达与生存的关系，并对所有蛋白质与临床病理特征进行相关性分析。
除了 p53，没有一种蛋白质具有预后意义。高 p53 表达对总生存和无病生存有明显影响。它也与病理完全缓解显著相关。p53 与局部复发也有高度相关性。另一方面，与 PTEN 表达和肿瘤反应呈高度相关性，但与生存无关。mLST8/REDD1、PTEN 和 NOXA 之间也存在强烈的相关性，证实了它们在同一级联中的作用。
p53 作为结直肠癌预后生物标志物的有争议作用得到了进一步证实，而 PTEN 和 REDD1 可能被认为是潜在的候选物。此外，NOXA 作为不同信号通路的连接元素出现。
