Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma
Abstract We used pyroptosis-related genes to establish a risk–score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA dat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-05-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10850-1 |
| _version_ | 1797832044939575296 |
|---|---|
| author | Xinyi Chen Mu Yang Lu Wang Yuan Wang Jingyao Tu Xiao Zhou Xianglin Yuan |
| author_facet | Xinyi Chen Mu Yang Lu Wang Yuan Wang Jingyao Tu Xiao Zhou Xianglin Yuan |
| author_sort | Xinyi Chen |
| collection | DOAJ |
| description | Abstract We used pyroptosis-related genes to establish a risk–score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA database. Through gene expression analyses, differentially expressed genes (DEGs) were determined. The 13 pyroptosis-related genes (PRGs) confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a PRGs prognostic signature, containing four PRGs (BAK1, GSDME, NLRP6, and NOD2) determined as independent prognostic factors. mRNA levels were evaluated by qRT-PCR, while overall survival (OS) rates were assessed by the Kaplan–Meier method. Enrichment analyses were done to establish the mechanisms associated with differential survival status of LIHC patients from a tumor immunology perspective. Additionally, a risk score determined by the prognostic model could divide LIHC patients into low- and high-risk groups using median risk score as cut-off. A prognostic nomogram, derived from the prognostic model and integrating clinical characteristics of patients, was constructed. The prognostic function of the model was also validated using GEO, ICGC cohorts, and online databases Kaplan–Meier Plotter. Small interfering RNA-mediated knockdown of GSDME, as well as lentivirus-mediated GSDME knockdown, were performed to validate that knockdown of GSDME markedly suppressed growth of HCC cells both in vivo and in vitro. Collectively, our study demonstrated a PRGs prognostic signature that had great clinical value in prognosis assessment. |
| first_indexed | 2024-04-09T14:02:32Z |
| format | Article |
| id | doaj.art-bc50548ef4a34c6694d8ac8e5ec143f3 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T14:02:32Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-bc50548ef4a34c6694d8ac8e5ec143f32023-05-07T11:15:55ZengBMCBMC Cancer1471-24072023-05-0123112310.1186/s12885-023-10850-1Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinomaXinyi Chen0Mu Yang1Lu Wang2Yuan Wang3Jingyao Tu4Xiao Zhou5Xianglin Yuan6Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract We used pyroptosis-related genes to establish a risk–score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA database. Through gene expression analyses, differentially expressed genes (DEGs) were determined. The 13 pyroptosis-related genes (PRGs) confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a PRGs prognostic signature, containing four PRGs (BAK1, GSDME, NLRP6, and NOD2) determined as independent prognostic factors. mRNA levels were evaluated by qRT-PCR, while overall survival (OS) rates were assessed by the Kaplan–Meier method. Enrichment analyses were done to establish the mechanisms associated with differential survival status of LIHC patients from a tumor immunology perspective. Additionally, a risk score determined by the prognostic model could divide LIHC patients into low- and high-risk groups using median risk score as cut-off. A prognostic nomogram, derived from the prognostic model and integrating clinical characteristics of patients, was constructed. The prognostic function of the model was also validated using GEO, ICGC cohorts, and online databases Kaplan–Meier Plotter. Small interfering RNA-mediated knockdown of GSDME, as well as lentivirus-mediated GSDME knockdown, were performed to validate that knockdown of GSDME markedly suppressed growth of HCC cells both in vivo and in vitro. Collectively, our study demonstrated a PRGs prognostic signature that had great clinical value in prognosis assessment.https://doi.org/10.1186/s12885-023-10850-1PyroptosisGSDMELiver hepatocellular carcinoma (LIHC)Prognostic signatureBioinformatics analysis |
| spellingShingle | Xinyi Chen Mu Yang Lu Wang Yuan Wang Jingyao Tu Xiao Zhou Xianglin Yuan Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma BMC Cancer Pyroptosis GSDME Liver hepatocellular carcinoma (LIHC) Prognostic signature Bioinformatics analysis |
| title | Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma |
| title_full | Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma |
| title_fullStr | Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma |
| title_full_unstemmed | Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma |
| title_short | Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma |
| title_sort | identification and in vitro and in vivo validation of the key role of gsdme in pyroptosis related genes signature in hepatocellular carcinoma |
| topic | Pyroptosis GSDME Liver hepatocellular carcinoma (LIHC) Prognostic signature Bioinformatics analysis |
| url | https://doi.org/10.1186/s12885-023-10850-1 |
| work_keys_str_mv | AT xinyichen identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT muyang identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT luwang identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT yuanwang identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT jingyaotu identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT xiaozhou identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma AT xianglinyuan identificationandinvitroandinvivovalidationofthekeyroleofgsdmeinpyroptosisrelatedgenessignatureinhepatocellularcarcinoma |