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在胰腺导管腺癌微环境中鉴定纺锤体和动粒相关家族基因作为治疗靶点和预后生物标志物

Identification of Spindle and Kinetochore-Associated Family Genes as Therapeutic Targets and Prognostic Biomarkers in Pancreas Ductal Adenocarcinoma Microenvironment.

作者信息

Liu Yi, Jin Zong-Rui, Huang Xing, Che Ye-Cheng, Liu Qin

机构信息

Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Guangxi Clinical Research Center for Colorectal Cancer, Nanning, China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

出版信息

Front Oncol. 2020 Nov 2;10:553536. doi: 10.3389/fonc.2020.553536. eCollection 2020.

DOI:10.3389/fonc.2020.553536
PMID:33224872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7667267/
Abstract

AIM

The role of spindle and kinetochore-associated (SKA) genes in tumorigenesis and cancer progression has been widely studied. However, so far, the oncogenic involvement of SKA family genes in pancreatic cancer and their prognostic potential remain unknown.

METHODS

Here, we carried out a meta-analysis of the differential expression of SKA genes in normal and tumor tissue. Univariate and multivariate survival analyses were done to evaluate the correlation between SKA family gene expression and pancreas ductal adenocarcinoma (PDAC) prognosis. Joint-effect and stratified survival analysis as well as nomogram analysis were used to estimate the prognostic value of genes. The underlying regulatory and biological mechanisms were identified by Gene set enrichment analysis. Interaction between SKA prognosis-related genes and immune cell infiltration was assessed using the Tumor Immune Estimation Resource tool.

RESULTS

We find that are highly expressed in PDAC tissues relative to non-cancer tissues. Survival analysis revealed that high expression of and independently indicate poor prognosis but they are not associated with relapse-free survival. The prognostic value of and was further confirmed by the nomogram, joint-effect, and stratified survival analysis. Analysis of underlying mechanisms reveals that these genes influence cancer-related signaling pathways, kinases, miRNA, and E2F family genes. Notably, prognosis-related genes are inversely correlated with several immune cells infiltrating levels.

CONCLUSION

We find that and expression correlates with prognosis and immune cell infiltration in PDAC, highlighting their potential as pancreatic cancer prognostic biomarkers.

摘要

目的

纺锤体和动粒相关（SKA）基因在肿瘤发生和癌症进展中的作用已得到广泛研究。然而，迄今为止，SKA家族基因在胰腺癌中的致癌作用及其预后潜力仍不清楚。

方法

在此，我们对SKA基因在正常组织和肿瘤组织中的差异表达进行了荟萃分析。进行单因素和多因素生存分析以评估SKA家族基因表达与胰腺导管腺癌（PDAC）预后之间的相关性。采用联合效应和分层生存分析以及列线图分析来评估基因的预后价值。通过基因集富集分析确定潜在的调控和生物学机制。使用肿瘤免疫评估资源工具评估SKA预后相关基因与免疫细胞浸润之间的相互作用。

结果

我们发现相对于非癌组织，[具体基因名称]在PDAC组织中高表达。生存分析显示，[具体基因名称]的高表达独立表明预后不良，但它们与无复发生存无关。列线图、联合效应和分层生存分析进一步证实了[具体基因名称]的预后价值。对潜在机制的分析表明，这些基因影响癌症相关信号通路、激酶、miRNA和E2F家族基因。值得注意的是，预后相关基因与几种免疫细胞浸润水平呈负相关。

结论

我们发现[具体基因名称]的表达与PDAC的预后和免疫细胞浸润相关，突出了它们作为胰腺癌预后生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc3/7667267/c7bf3d16af7c/fonc-10-553536-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc3/7667267/40e889f42e37/fonc-10-553536-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc3/7667267/c7bf3d16af7c/fonc-10-553536-g010.jpg

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SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis.SKA3 通过 EGFR-PI3K-Akt 轴促进肺腺癌转移。
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Ann Transl Med. 2021 Sep;9(17):1361. doi: 10.21037/atm-21-1572.
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Integrative Transcriptome Profiling Reveals as a Novel Prognostic Marker in Non-Muscle Invasive Bladder Cancer.综合转录组分析揭示了作为非肌层浸润性膀胱癌新的预后标志物。
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