Target gene analysis of PD-1 immunotherapy sensitivity in hepatocellular carcinoma
10.19405/j.cnki.issn1000-1492.2024.08.006
- Author:
Yuze Shi
1
,
2
;
Ke Ding
3
,
4
;
Beicheng Sun
1
,
2
,
4
Author Information
1. Dept of Hepatobiliary Surgery，The Affiliated Drum Tower Hospital of Nanjing University Medical School，Nanjing 210008
2. Dept of Hepatobiliary，Pancreatic and Transplantation Surgery， The First Affiliated Hospital of Anhui Medical University，Hefei 230022
3. Dept of Hepatobiliary，Pancreatic and Transplantation Surgery， The First Affiliated Hospital of Anhui Medical University，Hefei 230022
4. Dept of Hepatobiliary Surgery， Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University，Nanjing 210008
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma;
PD-1 immunotherapy;
BDH1;
tumor function experiment
- From:
Acta Universitatis Medicinalis Anhui
2024;59(8):1323-1329,1338
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the characteristic genes of Programmed cell death protein 1 ( PD-1) immuno- therapy sensitivity in Hepatocellular carcinoma ( HCC) ．
Methods :The common differential genes in GSE202069 and ERP117672 data sets were investigated by Weighted Gene Co-expression Network Analysis ( WGCNA) and Difference analysis，and the characteristic genes of PD-1 immunotherapy sensitivity were screened through Lasso regression．The expression levels of characteristic genes in HCC were predicted by GEPIA and Ualcan databases， and their expression was verified by real-time quantitative reverse transcription polymerase chain reaction ( RT- qPCR) ，Western blot (WB) and Immunohistochemistry (IHC) ．3-hydroxybutyrate dehydrogenase 1 (BDH1) over- expressed cell line was constructed，followed by cell counting kit-8 ( CCK-8) ，EdU，cell scratches and Transwell experiment to investigate the effects of BDH1 on the proliferation，migration and invasion of HCC cells.
Results:Total of 118 common differentially expressed genes were identified in two datasets by WGCNA and differential anal- ysis．The characteristic genes associated with PD-1 immunotherapy sensitivity screened through Lasso regression in- cluding Flavin containing dimethylaniline monoxygenase 3 ( FMO3 ) ，Peroxisomal trans-2-enoyl-CoA reductase (PECR) ，BDH1 ，Solute carrier family 7 member 1 ( SLC7A1 ) ，Cytochrome b5 type A ( CYB5A) and Phos- phoenolpyruvate carboxykinase 1 (PCK1) ． Survival analysis showed that BDH1 was most associated with HCC ( Overall survival : P＜0. 001，Recurrence : P = 0. 007) ．GEPIA and Ualcan databases showed low expression of BDH1 in HCC tissues，while RT-qPCR , WB，and IHC further confirmed this．CCK-8，plate cloning assay，EdU staining，cell scratch，and Transwell experiments showed that compared with the Hep3B pCDH group，overexpres- sion of BDH1 resulted in a decrease in the absorbance of HCC cells (t = 4. 766，P＜0. 01) ，a decrease in the num- ber of clone formation (t = 16. 02，P＜0. 000 1) ，a decrease in the proportion of proliferating cells (t = 23. 13，P ＜0. 000 1) ，a decrease in cell migration rate (t = 25. 28，P＜0. 000 1) ，and a decrease in the number of small compartments (t = 10. 78，P = 0. 004) ．
Conclusion :BDH1 is a characteristic gene for observing the sensitivity of PD-1 immunotherapy in HCC patients． BDH1 could inhibit the proliferation ，migration ，and invasion ability of HCC cells in vitro.
- Full text:2024091411273486946肝细胞癌PD-1免疫治疗敏感性的靶基因分析_史宇泽.pdf
