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解析乳腺癌中Hippo信号通路成分的基因表达谱。

Decoding gene expression profiles of Hippo signaling pathway components in breast cancer.

作者信息

Bhavnagari Hunayna M, Shah Franky D

机构信息

Life Science Department, Gujarat University, Ahmedabad, Gujarat, India.

Molecular Diagnostic and Research Lab-3, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.

出版信息

Mol Biol Rep. 2025 Feb 10;52(1):216. doi: 10.1007/s11033-025-10299-4.

Abstract

INTRODUCTION

The Hippo signaling pathway is an evolutionarily conserved, tumor suppressor, stem cell pathway. This is the very less explored pathway in Breast Cancer. It is a crucial regulator of several biological processes, such as organ size, differentiation, tissue homeostasis, cellular proliferation, and stemness. Interestingly, deregulation of this pathway leads to tumorigenesis. Hence, the present study aims to identify the role of the Hippo signaling pathway in Breast Cancer.

MATERIALS AND METHODS

The mRNA expression of the Hippo signaling pathway molecules was evaluated in 120 pre-therapeutic patients by quantitative real-time PCR. Statistical analysis was carried out using SPSS 23. The association between the gene expression and clinicopathological parameters was analyzed by the paired sample t-test, and Pearson chi-square test. ROC curve analysis was carried out using Med Cal. A p-value of ≤ 0.05 was considered statistically significant.

RESULTS

The hippo signaling pathway contains 10 core components i.e.SAV1, MOB1A, MOB1B, MST1, MST2, LATS1, LATS2, YAP, TAZ, and TEAD1 which were downregulated in malignant tissues as compared to adjacent normal tissue in breast cancer. In the correlation of hippo signaling pathway molecules with clinico pathological parameters, only LATS1, MST1, and SAV1 were found to be significantly negatively associated with stages of Breast Cancer. MOB1B was found to be significantly positively correlated with stages of Breast Cancer. ROC curve analysis of YAP, TAZ, LATS2, and TEAD showed significant discrimination between adjacent normal and malignant tissue.

CONCLUSION

In the current study, all the molecules of the hippo signaling pathway i.e. YAP, TAZ, LATS1, LATS2, MST1, MST2, SAV1, MOB1, MOB1B, TEAD1 were downregulated in BC suggesting the activation of hippo pathway which played a significant role in tumor suppression.

摘要

引言

河马信号通路是一条在进化上保守的肿瘤抑制干细胞通路。这是乳腺癌中研究较少的通路。它是多个生物学过程的关键调节因子,如器官大小、分化、组织稳态、细胞增殖和干性。有趣的是,该通路失调会导致肿瘤发生。因此,本研究旨在确定河马信号通路在乳腺癌中的作用。

材料与方法

通过定量实时PCR评估120例治疗前患者中河马信号通路分子的mRNA表达。使用SPSS 23进行统计分析。通过配对样本t检验和Pearson卡方检验分析基因表达与临床病理参数之间的关联。使用Med Cal进行ROC曲线分析。p值≤0.05被认为具有统计学意义。

结果

河马信号通路包含10个核心成分,即SAV1、MOB1A、MOB1B、MST1、MST2、LATS1、LATS2、YAP、TAZ和TEAD1,与乳腺癌相邻正常组织相比,这些成分在恶性组织中表达下调。在河马信号通路分子与临床病理参数的相关性分析中,仅发现LATS1、MST1和SAV1与乳腺癌分期显著负相关。发现MOB1B与乳腺癌分期显著正相关。YAP、TAZ、LATS2和TEAD的ROC曲线分析显示,相邻正常组织和恶性组织之间存在显著差异。

结论

在本研究中,河马信号通路的所有分子,即YAP、TAZ、LATS1、LATS2、MST1、MST2、SAV1、MOB1、MOB1B、TEAD1在乳腺癌中均下调,提示河马通路的激活在肿瘤抑制中起重要作用。

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