The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China.
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Pathol Res Pract. 2022 Apr;232:153808. doi: 10.1016/j.prp.2022.153808. Epub 2022 Feb 12.
Prefoldin complex subunits (PFDNs) and prefoldin-like complex subunits (PFDLNs) collaborate in protein folding, modulate endoplasmic reticulum stress. The association between PFDN/PFDLN and the immune microenvironment of HCC remains unclear. We investigated the biological significance of PFDNs and PFDLNs in HCC using bioinformatics.
The relationship between PFDNs/PFDLNs and HCC was analysed using TCGA, and Human Protein Atlas. The protein-protein interaction (PPI) network was performed through String and Cytoscape. In addition, mutations in PFDNs and PFDLNs were analysed using cBioPortal. Clinical correlation analysis, survival analysis was conducted by using UALCAN and Kaplan-Meier analysis. The protein-protein interaction (PPI) network was performed through String and Cytoscape. The GO and KEGG enrichment analyses were also carried out. CCK-8 and Flow cytometry analysis were used to detect the proliferation and apoptosis of PFDN1 and UXT knockdown HCC cells. Immune infiltrates analyses was were conducted using the TIMER and TISIDB to determine whether PFDNs/PFDLNs are predictive biomarkers of immune cell infiltration.
We observed that PFDNs and PFDLNs were significantly overexpressed in HCC tissues compared to normal liver tissues. This abnormal expression was associated with worse clinicopathological features and negatively affected patient survival. PFDNs and PFDLNs have varying degrees of mutations in HCC, which may be related to their abnormal expression. In addition, up-regulated PFDN1 and UXT were found to promote HCC proliferation and inhibit apoptosis in vitro. Finally, the expression of certain PFDNs and PFDLNs in the tumour microenvironment was positively correlated with the level of tumour-infiltrating immune cells and significantly enhanced the infiltration of immune cells in the microenvironment.
PFDNs and PFDLNs are valuable predictive biomarkers for immune infiltration in HCC and may assist in tumour immunotherapy research and prognosis prediction in the future.
原折叠酶复合物亚基（PFDNs）和原折叠酶样复合物亚基（PFDLNs）在蛋白质折叠中协作，并调节内质网应激。PFDN/PFDLN 与 HCC 的免疫微环境之间的关联尚不清楚。我们使用生物信息学方法研究了 PFDNs 和 PFDLNs 在 HCC 中的生物学意义。
使用 TCGA 和人类蛋白质图谱分析 PFDNs/PFDLNs 与 HCC 的关系。通过 String 和 Cytoscape 进行蛋白质-蛋白质相互作用（PPI）网络分析。此外，使用 cBioPortal 分析 PFDNs 和 PFDLNs 的突变。通过 UALCAN 和 Kaplan-Meier 分析进行临床相关性分析和生存分析。通过 String 和 Cytoscape 进行蛋白质-蛋白质相互作用（PPI）网络分析。还进行了 GO 和 KEGG 富集分析。使用 CCK-8 和流式细胞术分析检测 PFDN1 和 UXT 敲低 HCC 细胞的增殖和凋亡。使用 TIMER 和 TISIDB 进行免疫浸润分析，以确定 PFDNs/PFDLNs 是否是免疫细胞浸润的预测生物标志物。
我们观察到 PFDNs 和 PFDLNs 在 HCC 组织中明显过表达，与正常肝组织相比。这种异常表达与较差的临床病理特征相关，并对患者的生存产生负面影响。PFDNs 和 PFDLNs 在 HCC 中有不同程度的突变，这可能与其异常表达有关。此外，上调的 PFDN1 和 UXT 被发现促进 HCC 的增殖并抑制体外凋亡。最后，肿瘤微环境中某些 PFDNs 和 PFDLNs 的表达与肿瘤浸润免疫细胞的水平呈正相关，并显著增强了微环境中免疫细胞的浸润。
PFDNs 和 PFDLNs 是 HCC 免疫浸润的有价值的预测生物标志物，可能有助于未来的肿瘤免疫治疗研究和预后预测。
