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整合分析揭示 STC2 是喉鳞状细胞癌的预后生物标志物。

Integrative Analysis Reveals STC2 as a Prognostic Biomarker of Laryngeal Squamous Cell Carcinoma.

机构信息

School of Medicine, South China University of Technology, Guangzhou, China.

Department of Otorhinolaryngology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

出版信息

Appl Biochem Biotechnol. 2024 Jul;196(7):3891-3913. doi: 10.1007/s12010-023-04727-z. Epub 2023 Oct 4.

DOI:10.1007/s12010-023-04727-z
PMID:37792175
Abstract

Stanniocalcin 2 (STC2) is involved in many tumour types, but it remains unclear what its biological function is in laryngeal squamous cell carcinoma (LSCC). Therefore, we investigated STC2's expression, potential function, and prognostic significance of in LSCC. The expression and prognosis of STC2 in LSCC were described using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In the TCGA database, the relationship between STC2 and immune infiltration, expression of immune cell chemokine and receptor genes, immune cell molecular marker genes, and epithelial‒mesenchymal transition (EMT) marker genes were analysed. The biological processes involved in STC2 and its expression-related genes were analysed comprehensively using bioinformatics. The single-gene ceRNA network of STC2 was constructed in the TCGA database. Finally, LSCC patients' tumour tissue STC2 expression was verified. STC2 silencing with the RNAi technique was used for the determination of cellular functions in a laryngeal cancer cell line. STC2 expression was higher in most tumours, including LSCC, than in normal tissues and was associated with poor prognosis. The relative proportions of naïve B, plasma, follicular helper T, and macrophage M0 cells in LSCC and normal samples differed significantly. STC2 expression correlated significantly positively with that of TGFB1 (biomarker of Tregs) and significantly negatively with that of D79A and CD19 (biomarkers of B cells). Furthermore, STC2 affected chemokine and receptor gene expression in immune cells. STC2 expression correlated with EMT marker gene expression in LSCC. STC2 was enriched in the PI3K/AKT signalling pathway, extracellular matrix (ECM) organisation, ECM-receptor interaction, and other tumour-related signalling pathways. STC2 was highly expressed in our clinical samples. N-cadherin and vimentin expression were decreased in the TU686 cell line after successful silencing of STC2, indicating that high STC2 expression may prompt LSCC cells to adopt a mesenchymal cell phenotype. STC2 silencing substantially reduced proliferation and migration in the TU686 cell line. STC2 may be a promising predictive biomarker for tumours, providing new approaches for LSCC diagnosis and treatment monitoring.

摘要

钙结合蛋白 2(STC2)参与多种肿瘤类型,但在喉鳞状细胞癌(LSCC)中其生物学功能尚不清楚。因此,我们研究了 STC2 在 LSCC 中的表达、潜在功能和预后意义。使用基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库描述了 STC2 在 LSCC 中的表达和预后。在 TCGA 数据库中,分析了 STC2 与免疫浸润、免疫细胞趋化因子和受体基因、免疫细胞分子标志物基因以及上皮-间充质转化(EMT)标志物基因表达的关系。使用生物信息学综合分析了 STC2 及其表达相关基因涉及的生物学过程。在 TCGA 数据库中构建了 STC2 的单基因 ceRNA 网络。最后,验证了 LSCC 患者肿瘤组织中 STC2 的表达。使用 RNAi 技术沉默 STC2,以确定喉癌细胞系中的细胞功能。STC2 在大多数肿瘤中(包括 LSCC)的表达高于正常组织,与预后不良相关。LSCC 和正常样本中幼稚 B、浆细胞、滤泡辅助 T 和巨噬细胞 M0 的相对比例差异显著。STC2 表达与 TGFB1(Tregs 的标志物)呈显著正相关,与 D79A 和 CD19(B 细胞的标志物)呈显著负相关。此外,STC2 影响免疫细胞中趋化因子和受体基因的表达。STC2 表达与 LSCC 中 EMT 标志物基因的表达相关。STC2 在 PI3K/AKT 信号通路、细胞外基质(ECM)组织、ECM-受体相互作用和其他肿瘤相关信号通路中富集。我们的临床样本中 STC2 高表达。在 TU686 细胞系中成功沉默 STC2 后,N-钙粘蛋白和波形蛋白的表达降低,表明高 STC2 表达可能促使 LSCC 细胞呈现间充质细胞表型。STC2 沉默显著降低了 TU686 细胞系的增殖和迁移。STC2 可能是一种有前途的肿瘤预测生物标志物,为 LSCC 的诊断和治疗监测提供了新的方法。

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