Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma
Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118)...
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| Published in | Cancers Vol. 13; no. 22; p. 5623 |
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| Main Authors | , , , , , , , , , , |
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| Abstract | Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC. |
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| AbstractList | Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC. Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC. Simple SummaryRadioresistance is one of the major factors contributing to radiotherapy failure in OSCC. By systematically comparing the prognostic values of all genes in TCGA-OSCC patients with and without radiotherapy, radioresistance-associated genes were identified. Higher RPL36A transcript levels were found to be associated with a poor prognosis only in OSCC patients with radiotherapy in the cohort of TCGA and another independent Taiwanese cohort. RPL36A was then shown to be involved in the regulation of DNA damage, cell cycle and apoptosis, leading to radioresistance. Thus, such integrated studies are expected to be greatly beneficial for the development of new therapeutic interventions for radioresistant OSCC in the future.AbstractRadioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC. |
| Author | Cheng, Chun-Chia Chang, Kai-Ping Hong, Shu-Wen Cheng, Hsing-Wen Chen, Ting-Wen Sie, Zong-Lin Huang, Yenlin Liu, Shu-Chen Chen, Cheng-Yi Yen, Wei-Chen Wang, Chun-I |
| AuthorAffiliation | 2 Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan 3 Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan 10 Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 333, Taiwan 4 Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; dr.kpchang@gmail.com (K.-P.C.); aimee10221@gmail.com (H.-W.C.); d56610@yahoo.com.tw (W.-C.Y.) 7 Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan; cccheng.biocompare@gmail.com (C.-C.C.); g8935677@gmail.com (S.-W.H.); zonlins@gmail.com (Z.-L.S.) 9 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; louisyhuang@gmail.com 1 Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan; Dodochen@nctu.edu.tw 5 College of |
| AuthorAffiliation_xml | – name: 4 Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; dr.kpchang@gmail.com (K.-P.C.); aimee10221@gmail.com (H.-W.C.); d56610@yahoo.com.tw (W.-C.Y.) – name: 1 Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan; Dodochen@nctu.edu.tw – name: 8 Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; cychen@gs.ncku.edu.tw – name: 5 College of Medicine, Chang Gung University, Taoyuan 333, Taiwan – name: 10 Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 333, Taiwan – name: 2 Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan – name: 6 Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan – name: 9 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; louisyhuang@gmail.com – name: 7 Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan; cccheng.biocompare@gmail.com (C.-C.C.); g8935677@gmail.com (S.-W.H.); zonlins@gmail.com (Z.-L.S.) – name: 3 Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan |
| Author_xml | – sequence: 1 givenname: Ting-Wen orcidid: 0000-0003-4028-2375 surname: Chen fullname: Chen, Ting-Wen – sequence: 2 givenname: Kai-Ping orcidid: 0000-0003-1777-9578 surname: Chang fullname: Chang, Kai-Ping – sequence: 3 givenname: Chun-Chia orcidid: 0000-0002-6455-1798 surname: Cheng fullname: Cheng, Chun-Chia – sequence: 4 givenname: Cheng-Yi surname: Chen fullname: Chen, Cheng-Yi – sequence: 5 givenname: Shu-Wen surname: Hong fullname: Hong, Shu-Wen – sequence: 6 givenname: Zong-Lin orcidid: 0000-0002-3063-9927 surname: Sie fullname: Sie, Zong-Lin – sequence: 7 givenname: Hsing-Wen surname: Cheng fullname: Cheng, Hsing-Wen – sequence: 8 givenname: Wei-Chen surname: Yen fullname: Yen, Wei-Chen – sequence: 9 givenname: Yenlin surname: Huang fullname: Huang, Yenlin – sequence: 10 givenname: Shu-Chen surname: Liu fullname: Liu, Shu-Chen – sequence: 11 givenname: Chun-I orcidid: 0000-0001-8332-0162 surname: Wang fullname: Wang, Chun-I |
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| SubjectTerms | Antibiotics Apoptosis Bioinformatics Cancer therapies Cell cycle Datasets Deoxyribonucleic acid DNA DNA damage Genes Genomics Medical prognosis Oral carcinoma Oral cavity Oral squamous cell carcinoma Patients Prognosis Radiation therapy Radioresistance Radiosensitivity Therapeutic applications Transcription Tumors |
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| Title | Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma |
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