Clinicopathological effects of FOXO4 downregulation and FOXO6 upregulation in Indian breast cancer patients

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-04-02 DOI:10.1016/j.genrep.2025.102212

Sheersh Massey , Maria Habib , Samiha Saad , Arzoo Bano , Mohammad Aasif Khan , Syeda Maryam Husain , Sadaf , Kapil Dev , N.K. Shukla , Syed Akhtar Husain

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引用次数: 0

Abstract

FOXO (Forkhead box O) proteins modulates wide range of cellular functions including metabolism, longevity, growth and proliferation. Their aberrant expression, mutations or deletions are frequently reported in various human cancers making them crucial therapeutic candidates. In this study we aim to determine the expression pattern of comparatively less explored FOXO family proteins, FOXO4 and FOXO6 and their clinicopathological significance in Indian breast cancer patients. Breast tumor tissue and adjacent normal tissue samples were collected from the collaborating institute. FOXO4 and FOXO6 mRNA and protein expression were determined using Real Time PCR and Immunohistochemistry respectively. Further, GEPIA2 (Gene Expression Profiling Interactive Analysis 2) was used to corroborate the experimental results and prognostic significance of FOXO4 and FOXO6 was determined using KM-plotter. The mRNA expression of FOXO4 was found to be 3.25 fold downregulated while that of FOXO6 was 2.7 fold upregulated in breast cancer samples. The Immunohistochemistry results revealed weak expression of FOXO4 protein in 37 out of 52 cases and strong staining was observed for FOXO6 protein in 29 out of 52 cases. Lymph node status of the patients exhibited significant association with FOXO4 mRNA (p = 0.011) and protein level (p = 0.006). Whereas in case of FOXO6, enhanced expression showed substantial relation with ER status at protein level (p = 0.037) and with menopausal status of the patients at both mRNA (p = 0.042) and protein level (p = 0.015). Similar expression trend was observed in GEPIA2 database for both the genes. KM-plotter analysis further revealed that FOXO4 is significantly linked to relapse free survival of the patients. FOXO4 and FOXO6 genes manifest contrasting expression patterns, with lowered FOXO4 and elevated FOXO6 expression in Indian breast cancer samples. This study aims to provide insights into the clinical relevance of expression of both the genes. Future studies investigating their molecular interactions could be helpful in determining their relative significance as putative biomarkers in diagnosis and treatment of breast cancer.

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FOXO4下调和FOXO6上调在印度乳腺癌患者中的临床病理作用

FOXO （Forkhead box O）蛋白调节多种细胞功能，包括代谢、寿命、生长和增殖。它们的异常表达、突变或缺失在各种人类癌症中经常被报道，这使它们成为重要的治疗候选者。在本研究中，我们旨在确定相对较少探索的FOXO家族蛋白FOXO4和FOXO6在印度乳腺癌患者中的表达模式及其临床病理意义。乳腺肿瘤组织和邻近正常组织样本均来自合作研究所。采用Real Time PCR和免疫组织化学分别检测FOXO4和FOXO6 mRNA和蛋白的表达。进一步，采用GEPIA2（基因表达谱交互分析2）验证实验结果，并采用KM-plotter确定FOXO4和FOXO6的预后意义。在乳腺癌样本中，FOXO4 mRNA表达下调3.25倍，FOXO6 mRNA表达上调2.7倍。免疫组化结果显示，52例患者中37例FOXO4蛋白弱表达，29例FOXO6蛋白强染色。患者淋巴结状态与FOXO4 mRNA （p = 0.011）和FOXO4蛋白水平（p = 0.006）有显著相关性。而FOXO6的表达增强与ER蛋白水平（p = 0.037）、mRNA水平（p = 0.042）和蛋白水平（p = 0.015）相关。在GEPIA2数据库中，这两个基因的表达趋势相似。km -plot分析进一步显示FOXO4与患者的无复发生存率显著相关。FOXO4和FOXO6基因表现出不同的表达模式，在印度乳腺癌样本中FOXO4表达降低，FOXO6表达升高。本研究旨在为这两种基因表达的临床相关性提供见解。未来研究它们的分子相互作用可能有助于确定它们作为乳腺癌诊断和治疗的推定生物标志物的相对意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.