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全面分析黏着斑蛋白家族成员在非小细胞肺癌中的预后价值及其免疫浸润情况。

Comprehensive analysis of prognostic value and immune infiltration of kindlin family members in non-small cell lung cancer.

机构信息

Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Respirology Medicine Centre of Fujian Province, Quanzhou, China.

Department of Thoracic Surgery, Fuzhou Pulmonary Hospital, Fuzhou, China.

出版信息

BMC Med Genomics. 2021 May 2;14(1):119. doi: 10.1186/s12920-021-00967-2.

Abstract

BACKGROUND

Kindlin Family Members have been reported to be aberrantly expressed in various human cancer types and involved in tumorigenesis, tumor progression, and chemoresistance. However, their roles in non-small cell lung cancer (NSCLC) remain poorly elucidated.

METHODS

We analyzed the prognostic value and immune infiltration of Kindlins in NSCLC through Oncomine, GEPIA, UALCAN, CCLE, Kaplan‑Meier plotter, cBioPortal, TIMER, GeneMANIA, STRING, and DAVID database. Additionally, the mRNA expression levels of Kindlins were verified in 30 paired NSCLC tissues and NSCLC cell lines by real-time PCR.

RESULTS

The expression level of FERMT1 was remarkably increased in NSCLC tissues and NSCLC cell lines, while FERMT2 and FERMT3 were reduced. Kindlins expressions were associated with individual cancer stages and nodal metastasis. We also found that higher expression level of FERMT1 was obviously correlated with worse overall survival (OS) in patients with NSCLC, while higher FERMT2 was strongly associated with better overall survival (OS) and first progression (FP). Additionally, the expression of FERMT2 and FERMT3 were obviously correlated with the immune infiltration of diverse immune cells. Functional enrichment analysis has shown that Kindlins may be significantly correlated with intracellular signal transduction, ATP binding and the PI3K-Akt signaling pathway in NSCLC.

CONCLUSIONS

The research provides a new perspective on the distinct roles of Kindlins in NSCLC and likely has important implications for future novel biomarkers and therapeutic targets in NSCLC.

摘要

背景

Kindlin 家族成员在多种人类癌症类型中异常表达,并参与肿瘤发生、肿瘤进展和化疗耐药。然而,它们在非小细胞肺癌(NSCLC)中的作用仍未得到充分阐明。

方法

我们通过 Oncomine、GEPIA、UALCAN、CCLE、Kaplan-Meier plotter、cBioPortal、TIMER、GeneMANIA、STRING 和 DAVID 数据库分析了 Kindlins 在 NSCLC 中的预后价值和免疫浸润。此外,通过实时 PCR 验证了 30 对 NSCLC 组织和 NSCLC 细胞系中 Kindlins 的 mRNA 表达水平。

结果

FERMT1 在 NSCLC 组织和 NSCLC 细胞系中的表达水平显著增加,而 FERMT2 和 FERMT3 则减少。Kindlins 的表达与个体癌症分期和淋巴结转移有关。我们还发现,FERMT1 的高表达水平与 NSCLC 患者的总生存期(OS)明显相关,而 FERMT2 的高表达与总生存期(OS)和首次进展(FP)明显相关。此外,FERMT2 和 FERMT3 的表达与多种免疫细胞的免疫浸润明显相关。功能富集分析表明,Kindlins 可能与 NSCLC 中的细胞内信号转导、ATP 结合和 PI3K-Akt 信号通路显著相关。

结论

该研究为 Kindlins 在 NSCLC 中的不同作用提供了新的视角,并可能对 NSCLC 中未来新的生物标志物和治疗靶点具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a75/8091749/4bbee2980124/12920_2021_967_Fig1_HTML.jpg

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