Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India.
Department of General and Minimal Invasive Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India.
Pathol Res Pract. 2022 Mar;231:153791. doi: 10.1016/j.prp.2022.153791. Epub 2022 Jan 29.
TEAD4 transcription factor belonging to TEAD-family, is a key downstream element of the Hippo Signalling pathway and is very important for YAPinduced tumor progression. YAP-TEAD interaction is required to promote tumor progression and metastasis in various cancers. This study aims to investigate the role of TEAD4 in CRC progression and to compare the TEAD4 expression with different clinicopathological parameters of the study population. We also aim to explore the expression pattern of miR-4269 and miR-1343-3p and their functional role in TEAD4 mediated CRC progression. Furthermore, we intend to evaluate the prognostic significance of TEAD4, miR-4269, and miR-1343-3p in colorectal carcinoma.
Real-time PCR, Immunohistochemical Staining, and Western Blotting were performed on 71 human CRC tissue specimens and their adjacent normal tissues to evaluate the TEAD4 expression and the results were statistically analyzed against the clinicopathological variables of patient data and also with survival data using STATA software. miRNA expression was analyzed by quantitative real-time PCR.
TEAD4 expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with TNM stage, Duke Stage, tumor grade, invasion depth, node status, necrosis of tumor tissue, lymphovascular and perineural invasion. As per the cox-regression model and classification tree analysis, TNM stage and perineural invasion were important predictors for TEAD4 expression and prognosis of CRC patients. Survival analysis indicated that TEAD4 overexpression was associated with poorer overall and disease-free survival. miR-4269 and miR-1343-3p were downregulated in CRC tumors and showed a negative correlation with TEAD4. The nuclear overexpressed TEAD4 and downregulated miR-4269 and miR-1343-3p evaluated for the first time in CRC, are believed to serve as important prognostic markers in CRC.
Expression of TEAD4 was increased in CRC and was negatively regulated by miR-4269 and miR-1343-3p. The overexpression of TEAD4 is linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus TEAD4 may be a possible prognostic marker in CRC.
TEAD4 转录因子属于 TEAD 家族，是 Hippo 信号通路的关键下游元件，对于 YAP 诱导的肿瘤进展非常重要。YAP-TEAD 相互作用是促进各种癌症肿瘤进展和转移所必需的。本研究旨在探讨 TEAD4 在 CRC 进展中的作用，并比较研究人群中不同临床病理参数的 TEAD4 表达。我们还旨在探索 miR-4269 和 miR-1343-3p 的表达模式及其在 TEAD4 介导的 CRC 进展中的功能作用。此外，我们旨在评估 TEAD4、miR-4269 和 miR-1343-3p 在结直肠癌中的预后意义。
对 71 个人类 CRC 组织标本及其相邻正常组织进行实时 PCR、免疫组织化学染色和 Western Blotting，以评估 TEAD4 的表达，并使用 STATA 软件对患者数据的临床病理变量和生存数据进行统计学分析。通过定量实时 PCR 分析 miRNA 表达。
肿瘤标本中 TEAD4 的表达水平明显高于配对的正常标本。较高的蛋白表达水平与 TNM 分期、杜克分期、肿瘤分级、浸润深度、淋巴结状态、肿瘤组织坏死、血管淋巴管和神经周围侵犯显著相关。根据 cox 回归模型和分类树分析，TNM 分期和神经周围侵犯是 TEAD4 表达和 CRC 患者预后的重要预测因素。生存分析表明，TEAD4 过表达与整体和无病生存较差相关。miR-4269 和 miR-1343-3p 在 CRC 肿瘤中下调，并与 TEAD4 呈负相关。首次在 CRC 中评估核过表达的 TEAD4 和下调的 miR-4269 和 miR-1343-3p，被认为是 CRC 中的重要预后标志物。
CRC 中 TEAD4 的表达增加，受 miR-4269 和 miR-1343-3p 的负调控。TEAD4 的过表达与 CRC 患者整体和无病生存不良相关。这些发现支持先前的观察结果，因此 TEAD4 可能是 CRC 中的一个潜在预后标志物。
