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TCN1 是肺腺癌的一个潜在预后生物标志物,与免疫浸润相关。

TCN1 is a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma.

机构信息

Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No.215 Heping West Road, Shijiazhuang, Hebei Province, China.

出版信息

World J Surg Oncol. 2022 Mar 14;20(1):83. doi: 10.1186/s12957-022-02556-8.

Abstract

BACKGROUND

Around the world, lung cancer is the leading cause of cancer-related death. Lung adenocarcinomas are among the most common diagnosed forms of lung cancer, whose overall survival has not improved significantly, which makes finding an effective therapeutic target vital. Transcobalamin (TCN1) is a vitamin B12-binding protein which regulates cobalamin homeostasis. In tumor tissues, TCN1 is expressed highly, and its expression is correlated with cancer aggressiveness and poor prognosis according to recent studies and bioinformatic analyses. However, its effect on lung adenocarcinoma (LUAD) is unknown.

METHODS

We evaluated whether TCN1 shows diagnostic and prognostic value in LUAD using bioinformatic analysis. In particular, various databases and analysis tools were used to determine TCN1's relationship with LUAD, including TCGA, GTEx, GEO, STRING, and TISIDB.

RESULTS

As compared to normal lung tissue, the level of TCN1 expression in LUAD tissues was significantly higher (P < 0.001). TCN1 also had a good ability to distinguish lung adenocarcinoma from non-lung adenocarcinoma samples [area under the curve (AUC) = 0.788]. According to univariate Cox statistics, high expression levels of TCN1 correlate with poor overall survival (OS) in LUAD (P < 0.001). Moreover, based on a multivariate Cox analysis, TCN1 expression was independently correlated with OS (P = 0.011). GO/KEGG and GSEA indicated enrichment in epidermal cell differentiation (P < 0.0005), keratinocyte differentiation (P < 0.0005), neuroactive ligand-receptor interaction (P < 0.0005), epithelial-mesenchymal transition (P = 0.029, FDR = 0.023) and TNFA signaling via NFKB (P = 0.029, FDR = 0.023). Furthermore, TCN1 is associated with immune infiltration based on an analysis of immune cell infiltration.

CONCLUSIONS

In summary, TCN1 could be used as a prognostic and diagnostic biomarker and provide deeper perspectives for the development of therapies and prognostic markers in LUAD.

摘要

背景

在全球范围内,肺癌是癌症相关死亡的主要原因。肺腺癌是最常见的肺癌类型之一,其总体生存率没有显著提高,因此寻找有效的治疗靶点至关重要。转钴胺素(TCN1)是一种维生素 B12 结合蛋白,可调节钴胺素的体内平衡。根据最近的研究和生物信息学分析,在肿瘤组织中,TCN1 表达水平较高,其表达与癌症侵袭性和预后不良相关。然而,其对肺腺癌(LUAD)的影响尚不清楚。

方法

我们使用生物信息学分析评估 TCN1 在 LUAD 中的诊断和预后价值。具体来说,使用各种数据库和分析工具来确定 TCN1 与 LUAD 的关系,包括 TCGA、GTEx、GEO、STRING 和 TISIDB。

结果

与正常肺组织相比,LUAD 组织中 TCN1 的表达水平显著升高(P<0.001)。TCN1 还具有很好的区分肺腺癌和非肺腺癌样本的能力[曲线下面积(AUC)=0.788]。根据单因素 Cox 统计分析,TCN1 高表达与 LUAD 的总生存期(OS)不良相关(P<0.001)。此外,基于多因素 Cox 分析,TCN1 表达与 OS 独立相关(P=0.011)。GO/KEGG 和 GSEA 分析表明,TCN1 表达与表皮细胞分化(P<0.0005)、角质细胞分化(P<0.0005)、神经活性配体-受体相互作用(P<0.0005)、上皮-间充质转化(P=0.029, FDR=0.023)和 TNFA 信号通过 NFKB(P=0.029,FDR=0.023)相关。此外,基于免疫细胞浸润分析,TCN1 与免疫浸润相关。

结论

总之,TCN1 可作为 LUAD 的预后和诊断生物标志物,并为 LUAD 的治疗和预后标志物的开发提供更深入的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd55/8922850/edcf2eba9777/12957_2022_2556_Fig1_HTML.jpg

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