首页|ARL14在结直肠癌中的表达及其与肿瘤相关成纤维细胞浸润的关系

ARL14在结直肠癌中的表达及其与肿瘤相关成纤维细胞浸润的关系

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目的:探究二磷酸腺苷核糖基化因子样蛋白 14(adenosine diphosphate-ribosylation factor-like protein 14,ARL14)在结直肠癌(colorectal cancer,CRC)中的表达水平及其与肿瘤微环境中浸润细胞的关系.方法:分析TCGA-CRC数据集中 607例CRC组织与 51例正常组织中ARL14的表达差异及其与预后之间的关系,并预测参与上游表达调控的转录因子和miRNA.应用生物信息学方法分析ARL14表达与肿瘤微环境中各细胞浸润的关系.收集 2020年 1月至 2021年 1月于天津医科大学肿瘤医院院行手术治疗的 45 例CRC患者的肿瘤及配对正常组织,使用免疫组织化学染色检测ARL14、平滑肌肌动蛋白-α(smooth muscle actin-α,α-SMA)和成纤维细胞活化蛋白(fibroblast activation protein,FAP)的表达情况,验证ARL14表达与成纤维细胞活化的关系.结果:差异分析显示CRC中ARL14的表达量显著低于正常组织(P<0.001).与ARL14高表达患者相比,低表达患者的预后更差(P=0.025).MCPcounter分析显示ARL14表达与成纤维细胞的浸润呈负相关(P<0.0001).免疫组织化学染色结果显示ARL14在肿瘤中的表达显著低于正常组织(P<0.01),ARL14与间质中α-SMA、FAP的表达均为负相关.结论:ARL14可能在CRC中发挥肿瘤抑制基因的作用,并可能抑制成纤维细胞的活化.
ARL14 expression in colorectal cancer and its relationship with cancer associated fibro-blast infiltration
Objective:To investigated the strength of adenosine diphosphate ribosylation factor-like protein 14(ARL14)expression in colorectal cancer(CRC)and its relationship with major infiltrating cells in the tumor microenvironment.Methods:Data from the 607 CRC cases and 51 normal tissues in the TCGA-CRC dataset were analyzed.ARL14 mRNA expression levels were retrospectively collected and the relationship between ARL14 expression and CRC patient prognosis was analyzed.Transcription factors and miRNAs involved upstream in reg-ulating ARL14 expression were predicted.Bioinformatics methods were used to analyze the relationship between ARL14 expression and cell infiltration into the tumor microenvironment.Tumor and normal tissues from 45 CRC patients who underwent surgery in Tianjin Medical University Cancer Institute&Hospital from January 2020 to January 2021 were collected,and expression levels of ARL14,smooth muscle actin-α(α-SMA),and fibroblast-activated protein(FAP)were detected by immunohistochemical staining to verify the relationship between ARL14 expression and fibroblast activation.Results:Differential analysis showed that the ARL14 expression level was significantly lower in CRC tissues than in normal tissues(P<0.001).Patients with low ARL14 expression had worse prognosis than patients with high expression(Log-rank P=0.025).MCP-counter analysis showed that ARL14 expression correlated negatively with fibroblast infiltration(P<0.0001).Im-munohistochemical staining results showed that ARL14 expression was significantly lower in tumors than in normal tissues(P<0.01).ARL14 expression also correlated negatively with α-SMA and FAP expression levels in the interstitium.Conclusions:ARL14 may play a tumor sup-pressor role in CRC and inhibit fibroblast activation.

adenosine diphosphate-ribosylation factor-like protein 14(ARL14)colorectal cancer(CRC)cancer-associated fibroblaststumor microenvironment

卢成陆、孙燕

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天津医科大学肿瘤医院病理科,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市"肿瘤防治"重点实验室(天津市 300060)

ARL14 结直肠癌 肿瘤相关成纤维细胞 肿瘤微环境

国家自然科学基金面上项目天津市医学重点学科(专科)建设项目

81871990TJYXZDXK-012A

2024

中国肿瘤临床
中国抗癌协会

中国肿瘤临床

CSTPCD北大核心
影响因子:1.32
ISSN:1000-8179
年,卷(期):2024.51(4)