Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma
Abstract Background Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-024-11885-8 |
| _version_ | 1797276451935879168 |
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| author | Xia-Qing Li Shi-Qi Yin Lin Chen Aziguli Tulamaiti Shu-Yu Xiao Xue-Li Zhang Lei Shi Xiao-Cao Miao Yan Yang Xin Xing |
| author_facet | Xia-Qing Li Shi-Qi Yin Lin Chen Aziguli Tulamaiti Shu-Yu Xiao Xue-Li Zhang Lei Shi Xiao-Cao Miao Yan Yang Xin Xing |
| author_sort | Xia-Qing Li |
| collection | DOAJ |
| description | Abstract Background Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC. Methods RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8). Results The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups. Conclusion The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer. |
| first_indexed | 2024-03-07T15:28:25Z |
| format | Article |
| id | doaj.art-16fa3b92aed34f0c812c4ef4a107b219 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-07T15:28:25Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-16fa3b92aed34f0c812c4ef4a107b2192024-03-05T16:32:51ZengBMCBMC Cancer1471-24072024-01-0124111510.1186/s12885-024-11885-8Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinomaXia-Qing Li0Shi-Qi Yin1Lin Chen2Aziguli Tulamaiti3Shu-Yu Xiao4Xue-Li Zhang5Lei Shi6Xiao-Cao Miao7Yan Yang8Xin Xing9Anhui University of Science and Technology Affiliated Fengxian HospitalAnhui University of Science and Technology Affiliated Fengxian HospitalShanghai University of Medicine and Health Sciences Affiliated Sixth People’s Hospital South CampusState Key Laboratory of Systems Medicine for Cancer, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Systems Medicine for Cancer, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Systems Medicine for Cancer, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong UniversitySchool of Public Health, Lanzhou UniversityState Key Laboratory of Systems Medicine for Cancer, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Systems Medicine for Cancer, Ren Ji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityAnhui University of Science and Technology Affiliated Fengxian HospitalAbstract Background Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC. Methods RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8). Results The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups. Conclusion The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer.https://doi.org/10.1186/s12885-024-11885-8m6A-related lncRNAsPDACImmunotherapyPrognostic values |
| spellingShingle | Xia-Qing Li Shi-Qi Yin Lin Chen Aziguli Tulamaiti Shu-Yu Xiao Xue-Li Zhang Lei Shi Xiao-Cao Miao Yan Yang Xin Xing Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma BMC Cancer m6A-related lncRNAs PDAC Immunotherapy Prognostic values |
| title | Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| title_full | Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| title_fullStr | Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| title_full_unstemmed | Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| title_short | Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| title_sort | identification of a novel m6a related lncrnas signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma |
| topic | m6A-related lncRNAs PDAC Immunotherapy Prognostic values |
| url | https://doi.org/10.1186/s12885-024-11885-8 |
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