Department of General Surgery, Taizhou Municipal Hospital, Medical School of Taizhou University, Taizhou 318000, Zhejiang Province, China.
Departments of CyberKnife, Huashan Hospital, Fudan University, Shanghai 200032, China.
Int J Biol Sci. 2019 Jan 1;15(3):628-635. doi: 10.7150/ijbs.30652. eCollection 2019.
The Krüppel-like transcription factor 14 (KLF14) is a critical regulator of a wide array of biological processes. However, the role of KLF14 in colorectal cancer (CRC) isn't fully investigated. This study aimed to explore the clinicopathological significance and potential role of KLF14 in the carcinogenesis and progression of CRC. A tissue microarray consisting of 185 samples from stage I-III CRC patients was adopted to analyze the correlation between KLF14 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The underlying mechanisms of altered KLF14 expression on glycolysis were studied using and patients' samples. The results showed that KLF14 expression was downregulated in CRC than their normal controls. Low KLF14 expression correlated with advanced T stage (< 0.001) and N stage (= 0.040), and larger tumor size (= 0.008). Lost KLF14 expression implied shorter OS and DFS after colectomy in both univariate and multivariate survival analysis (<0.05). Experimentally, restore KLF14 expression significantly decreased the rate of glycolysis both and in patients' sample. Mechanically, KLF14 regulated glycolysis by downregulating glycolytic enzyme LDHB. Collectively, KLF14 is a novel prognostic biomarker for survival in CRC, and downregulation of KLF14 in CRC prompts glycolysis by target LDHB. Hence, KLF14 could constitute potential prognostic predictors and therapeutic targets for CRC.
Krüppel 样转录因子 14(KLF14)是广泛生物过程的关键调节因子。然而,KLF14 在结直肠癌(CRC)中的作用尚未完全研究。本研究旨在探索 KLF14 在 CRC 发生和发展中的临床病理意义和潜在作用。采用包含 185 例 I-III 期 CRC 患者的组织微阵列来分析 KLF14 表达与临床病理参数以及总生存期(OS)和无病生存期(DFS)之间的相关性。使用 和患者样本研究了 KLF14 表达改变对糖酵解的潜在机制。结果表明,CRC 中的 KLF14 表达低于其正常对照。低 KLF14 表达与较晚的 T 分期(<0.001)和 N 分期(=0.040)以及更大的肿瘤大小(=0.008)相关。在单变量和多变量生存分析中,KLF14 缺失表达提示结直肠切除术后 OS 和 DFS 较短(<0.05)。实验上,恢复 KLF14 表达可显著降低 和患者样本中的糖酵解率。机制上,KLF14 通过下调糖酵解酶 LDHB 来调节糖酵解。总之,KLF14 是 CRC 生存的新型预后生物标志物,CRC 中 KLF14 的下调通过靶标 LDHB 促进糖酵解。因此,KLF14 可能构成 CRC 的潜在预后预测因子和治疗靶点。