Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity
Purpose: Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stag...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.724889/full |
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| author | Zhizhong Xiong Zhizhong Xiong Xianzhe Li Xianzhe Li Shi Yin Shi Yin Minghao Xie Minghao Xie Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Lei Lian Lei Lian |
| author_facet | Zhizhong Xiong Zhizhong Xiong Xianzhe Li Xianzhe Li Shi Yin Shi Yin Minghao Xie Minghao Xie Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Lei Lian Lei Lian |
| author_sort | Zhizhong Xiong |
| collection | DOAJ |
| description | Purpose: Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stage (stages I and II) colorectal cancer (CRC).Methods: m6A-related lncRNA data were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen for prognostic m6A-related lncRNAs. Immune characteristics were analyzed in different subgroups created via unsupervised clustering analysis. Next, patients were randomly divided into training and test cohorts. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was performed to establish a prognostic model. The predictive value of the signature was evaluated in the training and test cohorts. Drug sensitivity was also examined.Results: A total of 1,478 m6A-related lncRNAs were identified. Two subgroups were created based on the expression of seven prognostic m6A-related lncRNAs. Prognosis was worse for cluster 1 than for cluster 2, and cluster 1 was characterized by increased numbers of M2 macrophages, decreased numbers of memory B cells, and higher expression of checkpoint genes when compared with cluster 2. Five m6A-related lncRNAs were selected to establish a risk prediction signature via LASSO regression. The 3 years overall survival (OS) was higher in the low-risk group than in the high-risk group. The area under the curve at 1, 2, and 3 years was 0.929, 0.954, and 0.841 in the training cohort and 0.664, 0.760, and 0.754 in the test cohort, respectively. Multivariate Cox regression analysis suggests that the risk score was an independent predictor of OS in both the training and test cohorts. A prognostic nomogram based on the five m6A-related lncRNAs and their clinical features was built and verified. The high-risk group was more sensitive to chemotherapeutic drugs (camptothecin and cisplatin) than the low-risk group.Conclusion: We identified two molecular subgroups of early-stage CRC with unique immune features based on seven prognostic m6A-related lncRNAs. Subsequent analyses demonstrated the usefulness of a five m6A-related lncRNA signature as a potential indicator of prognosis in patients with early-stage CRC. |
| first_indexed | 2024-12-22T08:29:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-22T08:29:58Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-86f6eb53ce404bcaaa66ee3a4535c6572022-12-21T18:32:31ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-10-01810.3389/fmolb.2021.724889724889Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug SensitivityZhizhong Xiong0Zhizhong Xiong1Xianzhe Li2Xianzhe Li3Shi Yin4Shi Yin5Minghao Xie6Minghao Xie7Chaobin Mao8Fengxiang Zhang9Huaxian Chen10Huaxian Chen11Longyang Jin12Lei Lian13Lei Lian14Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaPurpose: Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stage (stages I and II) colorectal cancer (CRC).Methods: m6A-related lncRNA data were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen for prognostic m6A-related lncRNAs. Immune characteristics were analyzed in different subgroups created via unsupervised clustering analysis. Next, patients were randomly divided into training and test cohorts. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was performed to establish a prognostic model. The predictive value of the signature was evaluated in the training and test cohorts. Drug sensitivity was also examined.Results: A total of 1,478 m6A-related lncRNAs were identified. Two subgroups were created based on the expression of seven prognostic m6A-related lncRNAs. Prognosis was worse for cluster 1 than for cluster 2, and cluster 1 was characterized by increased numbers of M2 macrophages, decreased numbers of memory B cells, and higher expression of checkpoint genes when compared with cluster 2. Five m6A-related lncRNAs were selected to establish a risk prediction signature via LASSO regression. The 3 years overall survival (OS) was higher in the low-risk group than in the high-risk group. The area under the curve at 1, 2, and 3 years was 0.929, 0.954, and 0.841 in the training cohort and 0.664, 0.760, and 0.754 in the test cohort, respectively. Multivariate Cox regression analysis suggests that the risk score was an independent predictor of OS in both the training and test cohorts. A prognostic nomogram based on the five m6A-related lncRNAs and their clinical features was built and verified. The high-risk group was more sensitive to chemotherapeutic drugs (camptothecin and cisplatin) than the low-risk group.Conclusion: We identified two molecular subgroups of early-stage CRC with unique immune features based on seven prognostic m6A-related lncRNAs. Subsequent analyses demonstrated the usefulness of a five m6A-related lncRNA signature as a potential indicator of prognosis in patients with early-stage CRC.https://www.frontiersin.org/articles/10.3389/fmolb.2021.724889/fullearly-stage colorectal cancerlong non-coding RNAN6-methyladenosinenomogramprognosis |
| spellingShingle | Zhizhong Xiong Zhizhong Xiong Xianzhe Li Xianzhe Li Shi Yin Shi Yin Minghao Xie Minghao Xie Chaobin Mao Fengxiang Zhang Huaxian Chen Huaxian Chen Longyang Jin Lei Lian Lei Lian Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity Frontiers in Molecular Biosciences early-stage colorectal cancer long non-coding RNA N6-methyladenosine nomogram prognosis |
| title | Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity |
| title_full | Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity |
| title_fullStr | Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity |
| title_full_unstemmed | Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity |
| title_short | Prognostic Value of N6-Methyladenosine-Related lncRNAs in Early-Stage Colorectal Cancer: Association With Immune Cell Infiltration and Chemotherapeutic Drug Sensitivity |
| title_sort | prognostic value of n6 methyladenosine related lncrnas in early stage colorectal cancer association with immune cell infiltration and chemotherapeutic drug sensitivity |
| topic | early-stage colorectal cancer long non-coding RNA N6-methyladenosine nomogram prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.724889/full |
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