Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma
Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1073770/full |
| _version_ | 1797951455493095424 |
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| author | Jiezhang Tang Xuechen Wu Bo Cheng Yajie Lu |
| author_facet | Jiezhang Tang Xuechen Wu Bo Cheng Yajie Lu |
| author_sort | Jiezhang Tang |
| collection | DOAJ |
| description | Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC. |
| first_indexed | 2024-04-10T22:30:51Z |
| format | Article |
| id | doaj.art-8fe21fc6eb5641dfa35077ce40e6b04d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T22:30:51Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-8fe21fc6eb5641dfa35077ce40e6b04d2023-01-17T05:23:19ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-01-011010.3389/fmolb.2023.10737701073770Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinomaJiezhang Tang0Xuechen Wu1Bo Cheng2Yajie Lu3Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaElevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1073770/fulloral squamous cell carcinomabioinformatics analysesThe Cancer Genome Atlaspolyaminesprognostic modelimmune infiltration |
| spellingShingle | Jiezhang Tang Xuechen Wu Bo Cheng Yajie Lu Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma Frontiers in Molecular Biosciences oral squamous cell carcinoma bioinformatics analyses The Cancer Genome Atlas polyamines prognostic model immune infiltration |
| title | Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| title_full | Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| title_fullStr | Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| title_full_unstemmed | Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| title_short | Identification of a polyamine-related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| title_sort | identification of a polyamine related signature and six novel prognostic biomarkers in oral squamous cell carcinoma |
| topic | oral squamous cell carcinoma bioinformatics analyses The Cancer Genome Atlas polyamines prognostic model immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1073770/full |
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