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SEC14L4在食管鳞状细胞癌中的作用:对临床相关性和分子途径的见解。

The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways.

作者信息

Wang An, Wang Youbo, Chen Yanhui, Wan Posum, Saeed Anwaar, Ma Qinyun, Chen Xiaofeng

机构信息

Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Department of Nursing, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Transl Cancer Res. 2024 Oct 31;13(10):5535-5549. doi: 10.21037/tcr-24-1657. Epub 2024 Oct 29.

DOI:10.21037/tcr-24-1657
PMID:39525030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11543032/
Abstract

BACKGROUND

Esophageal squamous cell cancer (ESCC) is the most common type of esophageal cancer. This study aimed to elucidate the role of Saccharomyces cerevisiae-like 4 () in ESCC.

METHODS

To elucidate the role of in ESCC, this study analyzed the clinical data, gene sequencing data, and other relevant data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of the National Center for Biotechnology Information. The methodology involved several analytical approaches, including nomogram model analysis, co-expression analysis, gene set enrichment and variation analysis, weighted correlation network analysis, drug susceptibility analysis, and single-cell analysis. These methods were employed to evaluate the significance of SEC14L4 in ESCC. The expression of was evaluated via quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

expression (P<0.001) was significantly elevated in those with ESCC, especially in patients with locally advanced disease (P=0.005), and indicated a poor prognosis (P=0.045). Findings from the nomogram model analysis identified the contribution of clinical indicators to survival prediction with good efficacy. Subsequently, the single-nucleotide polymorphisms and co-expressed genes of were identified. Furthermore, pathways associated with , including DNA metabolic process, transcription factor binding, apoptosis, and others, were examined. Notably, expression was predominantly observed in monocytes. Drug sensitivity analysis indicated the association of expression with sensitivity of ESCC to the common chemotherapy drugs AICAR, BMS.708163, GNF.2, Nutlin.3a, PD.0325901, and RDEA119. Verification of the high expression of in KYSE520 and KYSE150 was conducted, thereby confirming the study's findings.

CONCLUSIONS

High expression of SEC14L4 is associated with poorer clinical outcomes, highlighting its potential as a therapeutic target and suggesting its involvement in the molecular mechanisms underlying ESCC.

摘要

背景

食管鳞状细胞癌(ESCC)是食管癌最常见的类型。本研究旨在阐明酵母样蛋白4(SEC14L4)在ESCC中的作用。

方法

为阐明SEC14L4在ESCC中的作用,本研究分析了从美国国立生物技术信息中心的癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中检索到的临床数据、基因测序数据及其他相关数据。该方法涉及多种分析方法,包括列线图模型分析、共表达分析、基因集富集与变异分析、加权相关网络分析、药物敏感性分析和单细胞分析。这些方法用于评估SEC14L4在ESCC中的意义。通过定量实时聚合酶链反应(qRT-PCR)评估SEC14L4的表达。

结果

SEC14L4表达在ESCC患者中显著升高(P<0.001),尤其是局部晚期疾病患者(P=0.005),且提示预后不良(P=0.045)。列线图模型分析结果确定了临床指标对生存预测的贡献,疗效良好。随后,鉴定了SEC14L4的单核苷酸多态性和共表达基因。此外,还研究了与SEC14L4相关的途径,包括DNA代谢过程、转录因子结合、凋亡等。值得注意的是,SEC14L4表达主要在单核细胞中观察到。药物敏感性分析表明SEC14L4表达与ESCC对常用化疗药物AICAR、BMS.708163、GNF.2、Nutlin.3a、PD.0325901和RDEA119的敏感性相关。对KYSE520和KYSE150中SEC14L4高表达进行了验证,从而证实了该研究的结果。

结论

SEC14L4高表达与较差的临床结局相关,突出了其作为治疗靶点的潜力,并提示其参与了ESCC的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/86eae8a87dca/tcr-13-10-5535-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/82e3fcbdab2a/tcr-13-10-5535-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/60f383bb88c6/tcr-13-10-5535-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/9426854bcade/tcr-13-10-5535-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/e24d222d97cb/tcr-13-10-5535-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/27ff3d60d23f/tcr-13-10-5535-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/e80c9629d353/tcr-13-10-5535-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/8ea2bd2ea6bd/tcr-13-10-5535-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/3dd65d9f0380/tcr-13-10-5535-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/86eae8a87dca/tcr-13-10-5535-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/82e3fcbdab2a/tcr-13-10-5535-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/60f383bb88c6/tcr-13-10-5535-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/9426854bcade/tcr-13-10-5535-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/e24d222d97cb/tcr-13-10-5535-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/27ff3d60d23f/tcr-13-10-5535-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/e80c9629d353/tcr-13-10-5535-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/8ea2bd2ea6bd/tcr-13-10-5535-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/3dd65d9f0380/tcr-13-10-5535-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9229/11543032/86eae8a87dca/tcr-13-10-5535-f9.jpg

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