Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC
Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with a poor prognosis. Identifying reliable prognostic biomarkers and therapeutic targets is crucial for improving patient outcomes. This study aimed to systematically identify proliferation-essential...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14181-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849709600208584704 |
|---|---|
| author | Ke-ling Pang Pian Li Xiang-Rong Yao Wen-Tao Xiao Xing Ren Jun-Yan He |
| author_facet | Ke-ling Pang Pian Li Xiang-Rong Yao Wen-Tao Xiao Xing Ren Jun-Yan He |
| author_sort | Ke-ling Pang |
| collection | DOAJ |
| description | Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with a poor prognosis. Identifying reliable prognostic biomarkers and therapeutic targets is crucial for improving patient outcomes. This study aimed to systematically identify proliferation-essential genes (PEGs) associated with HNSCC prognosis using CRISPR-Cas9 screening data. Methods CRISPR-Cas9 screening data from the DepMap database were used to identify PEGs in HNSCC cells. A prognostic PEGs signature was constructed using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression analyses. The predictive accuracy of the signature was validated in internal and external datasets. Weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and immune infiltration analysis were used to investigate the underlying mechanism between high and low-risk patients. Random forest analysis and functional experiments were conducted to investigate the role of key proliferation essential genes in HNSCC progression. Results A total of 1511 PEGs were identified. A seven-gene prognostic PEGs signature (MRPL33, NAT10, PSMC1, PSMD11, RPN2, TAF7, and ZNF335) was developed and validated, demonstrating robust prognostic performance in stratifying HNSCC patients by survival risk. WGCNA and GSEA analyses revealed a marked downregulation of immune-related pathways in high-risk patients. Immune infiltration analysis validated those high-risk patients had reduced immune scores, stromal scores, and ESTIMATE scores, as well as decreased infiltration of multiple immune cell types. Among the identified genes, PSMC1 was highlighted as a pivotal regulator of HNSCC proliferation and migration, as confirmed by functional experiments. Conclusions This study identifies a novel PEGs signature that effectively predicts HNSCC prognosis and stratifies patients by survival risk. PSMC1 was identified as a key gene promoting malignant progression, offering potential as a therapeutic target for HNSCC. |
| format | Article |
| id | doaj-art-dbc65d510dbe4433b4fb0599360fe6b8 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-dbc65d510dbe4433b4fb0599360fe6b82025-08-20T03:15:13ZengBMCBMC Cancer1471-24072025-04-0125112010.1186/s12885-025-14181-1Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCCKe-ling Pang0Pian Li1Xiang-Rong Yao2Wen-Tao Xiao3Xing Ren4Jun-Yan He5Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaClinical Laboratory Medicine Center, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaAbstract Background Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with a poor prognosis. Identifying reliable prognostic biomarkers and therapeutic targets is crucial for improving patient outcomes. This study aimed to systematically identify proliferation-essential genes (PEGs) associated with HNSCC prognosis using CRISPR-Cas9 screening data. Methods CRISPR-Cas9 screening data from the DepMap database were used to identify PEGs in HNSCC cells. A prognostic PEGs signature was constructed using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression analyses. The predictive accuracy of the signature was validated in internal and external datasets. Weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and immune infiltration analysis were used to investigate the underlying mechanism between high and low-risk patients. Random forest analysis and functional experiments were conducted to investigate the role of key proliferation essential genes in HNSCC progression. Results A total of 1511 PEGs were identified. A seven-gene prognostic PEGs signature (MRPL33, NAT10, PSMC1, PSMD11, RPN2, TAF7, and ZNF335) was developed and validated, demonstrating robust prognostic performance in stratifying HNSCC patients by survival risk. WGCNA and GSEA analyses revealed a marked downregulation of immune-related pathways in high-risk patients. Immune infiltration analysis validated those high-risk patients had reduced immune scores, stromal scores, and ESTIMATE scores, as well as decreased infiltration of multiple immune cell types. Among the identified genes, PSMC1 was highlighted as a pivotal regulator of HNSCC proliferation and migration, as confirmed by functional experiments. Conclusions This study identifies a novel PEGs signature that effectively predicts HNSCC prognosis and stratifies patients by survival risk. PSMC1 was identified as a key gene promoting malignant progression, offering potential as a therapeutic target for HNSCC.https://doi.org/10.1186/s12885-025-14181-1Head and neck squamous cell carcinomaCRISPR-Cas9 screeningProliferation-essential genesPrognostic signatureTumor immune microenvironmentPSMC1 |
| spellingShingle | Ke-ling Pang Pian Li Xiang-Rong Yao Wen-Tao Xiao Xing Ren Jun-Yan He Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC BMC Cancer Head and neck squamous cell carcinoma CRISPR-Cas9 screening Proliferation-essential genes Prognostic signature Tumor immune microenvironment PSMC1 |
| title | Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC |
| title_full | Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC |
| title_fullStr | Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC |
| title_full_unstemmed | Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC |
| title_short | Deciphering a proliferation-essential gene signature based on CRISPR-Cas9 screening to predict prognosis and characterize the immune microenvironment in HNSCC |
| title_sort | deciphering a proliferation essential gene signature based on crispr cas9 screening to predict prognosis and characterize the immune microenvironment in hnscc |
| topic | Head and neck squamous cell carcinoma CRISPR-Cas9 screening Proliferation-essential genes Prognostic signature Tumor immune microenvironment PSMC1 |
| url | https://doi.org/10.1186/s12885-025-14181-1 |
| work_keys_str_mv | AT kelingpang decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc AT pianli decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc AT xiangrongyao decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc AT wentaoxiao decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc AT xingren decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc AT junyanhe decipheringaproliferationessentialgenesignaturebasedoncrisprcas9screeningtopredictprognosisandcharacterizetheimmunemicroenvironmentinhnscc |