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程序性细胞死亡2样蛋白(PDCD2L)致癌作用的泛癌分析及在结直肠癌中的验证

Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer.

作者信息

Gao Huabin, Xu Cheng, Liang Jiangtao, Ge Songhan, Zhang Fenfen, Tuo Ying, Shi Huijuan, Han Anjia

机构信息

Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, 58, Zhongshan Road II, Guangzhou, 510080, China.

出版信息

Cancer Cell Int. 2022 Feb 25;22(1):100. doi: 10.1186/s12935-022-02525-x.

Abstract

BACKGROUND

Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear.

METHODS

Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers.

RESULTS

Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells.

CONCLUSIONS

Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

摘要

背景

程序性细胞死亡2样蛋白(PDCD2L)与细胞增殖、凋亡及小鼠胚胎发育相关。然而,PDCD2L在人类癌症中的作用尚不清楚。

方法

采用多种生物信息学方法、体外功能实验及验证,以阐明PDCD2L在人类癌症中的致癌作用。

结果

我们的研究发现,PDCD2L在多种人类癌症中异常表达,并与临床分期和分子亚型相关。此外,PDCD2L过表达预示肾上腺皮质癌(ACC)、肾嫌色细胞癌(KICH)、急性髓系白血病(LAML)、脑低级别胶质瘤(LGG)、肝细胞肝癌(LIHC)、间皮瘤(MESO)、葡萄膜黑色素瘤(UVM)患者总生存期较差,以及ACC、膀胱尿路上皮癌(BLCA)、宫颈鳞状细胞癌和宫颈管腺癌(CESC)、肾透明细胞癌(KIRC)、肾乳头状细胞癌(KIRP)、LGG、LIHC及UVM患者无病生存期较差。在乳腺浸润性癌(BRCA)、肺鳞状细胞癌(LUSC)、肉瘤(SARC)、胃腺癌(STAD)和睾丸生殖细胞肿瘤(TGCT)中,PDCD2L表达与癌症相关成纤维细胞呈负相关。机制上,通过研究单细胞测序数据,我们发现PDCD2L表达与凋亡、侵袭和细胞周期相关。为进一步验证,与正常结肠细胞系和非肿瘤邻近结直肠黏膜组织相比,PDCD2L在结直肠癌(CRC)细胞系和组织样本中高表达。敲低PDCD2L可诱导CRC细胞凋亡和增殖。

结论

我们的研究表明,PDCD2L在多种癌症中具有致癌作用,且可作为CRC的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450d/8881831/190bb52124c7/12935_2022_2525_Fig1_HTML.jpg

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