Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer
Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.989646/full |
| _version_ | 1828377781480718336 |
|---|---|
| author | Xinyu Liu Xinyu Liu Lei Zhou Minghui Gao Minghui Gao Shuhong Dong Shuhong Dong Yanan Hu Yanan Hu Chunjie Hu Chunjie Hu |
| author_facet | Xinyu Liu Xinyu Liu Lei Zhou Minghui Gao Minghui Gao Shuhong Dong Shuhong Dong Yanan Hu Yanan Hu Chunjie Hu Chunjie Hu |
| author_sort | Xinyu Liu |
| collection | DOAJ |
| description | Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients. |
| first_indexed | 2024-04-14T08:17:25Z |
| format | Article |
| id | doaj.art-80cc84ba2faa47b7901a61dabb16432a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T08:17:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-80cc84ba2faa47b7901a61dabb16432a2022-12-22T02:04:21ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.989646989646Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancerXinyu Liu0Xinyu Liu1Lei Zhou2Minghui Gao3Minghui Gao4Shuhong Dong5Shuhong Dong6Yanan Hu7Yanan Hu8Chunjie Hu9Chunjie Hu10Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, ChinaDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, ChinaDepartment of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, ChinaDepartment of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, ChinaDepartment of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, ChinaBackground: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.https://www.frontiersin.org/articles/10.3389/fgene.2022.989646/fullcuproptosislncRNAcervical cancerprognosisimmunotherapytargeted therapy |
| spellingShingle | Xinyu Liu Xinyu Liu Lei Zhou Minghui Gao Minghui Gao Shuhong Dong Shuhong Dong Yanan Hu Yanan Hu Chunjie Hu Chunjie Hu Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer Frontiers in Genetics cuproptosis lncRNA cervical cancer prognosis immunotherapy targeted therapy |
| title | Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| title_full | Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| title_fullStr | Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| title_full_unstemmed | Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| title_short | Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| title_sort | signature of seven cuproptosis related lncrnas as a novel biomarker to predict prognosis and therapeutic response in cervical cancer |
| topic | cuproptosis lncRNA cervical cancer prognosis immunotherapy targeted therapy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.989646/full |
| work_keys_str_mv | AT xinyuliu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT xinyuliu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT leizhou signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT minghuigao signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT minghuigao signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT shuhongdong signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT shuhongdong signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT yananhu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT yananhu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT chunjiehu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer AT chunjiehu signatureofsevencuproptosisrelatedlncrnasasanovelbiomarkertopredictprognosisandtherapeuticresponseincervicalcancer |