Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer
Aberrant sialylation plays a key biological role in tumorigenesis and metastasis, including tumor cell survival and invasion, immune evasion, angiogenesis, and resistance to therapy. It has been proposed as a possible cancer biomarker and a potential therapeutic target of tumors. Nevertheless, the p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.994874/full |
| _version_ | 1811341385264005120 |
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| author | Mingxuan Zhou Silin Lv Yufang Hou Rixin Zhang Weiqi Wang Zheng Yan Tiegang Li Wenqiang Gan Zifan Zeng Fang Zhang Min Yang |
| author_facet | Mingxuan Zhou Silin Lv Yufang Hou Rixin Zhang Weiqi Wang Zheng Yan Tiegang Li Wenqiang Gan Zifan Zeng Fang Zhang Min Yang |
| author_sort | Mingxuan Zhou |
| collection | DOAJ |
| description | Aberrant sialylation plays a key biological role in tumorigenesis and metastasis, including tumor cell survival and invasion, immune evasion, angiogenesis, and resistance to therapy. It has been proposed as a possible cancer biomarker and a potential therapeutic target of tumors. Nevertheless, the prognostic significance and biological features of sialylation-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remain unclear. This study aimed to develop a novel sialylation-related lncRNA signature to accurately evaluate the prognosis of patients with CRC and explore the potential molecular mechanisms of the sialylation-related lncRNAs. Here, we identified sialylation-related lncRNAs using the Pearson correlation analysis on The Cancer Genome Atlas (TCGA) dataset. Univariate and stepwise multivariable Cox analysis were used to establish a signature based on seven sialylation-related lncRNAs in the TCGA dataset, and the risk model was validated in the Gene Expression Omnibus dataset. Kaplan-Meier curve analysis revealed that CRC patients in the low-risk subgroup had a better survival outcome than those in the high-risk subgroup in the training set, testing set, and overall set. Multivariate analysis demonstrated that the sialylation-related lncRNA signature was an independent prognostic factor for overall survival, progression-free survival, and disease-specific survival prediction. The sialylation lncRNA signature-based nomogram exhibited a robust prognostic performance. Furthermore, enrichment analysis showed that cancer hallmarks and oncogenic signaling were enriched in the high-risk group, while inflammatory responses and immune-related pathways were enriched in the low-risk group. The comprehensive analysis suggested that low-risk patients had higher activity of immune response pathways, greater immune cell infiltration, and higher expression of immune stimulators. In addition, we determined the sialylation level in normal colonic cells and CRC cell lines by flow cytometry combined with immunofluorescence, and verified the expression levels of seven lncRNAs using real-time quantitative polymerase chain reaction. Finally, combined drug sensitivity analysis using the Genomics of Drug Sensitivity in Cancer, Cancer Therapeutics Response Portal, and Profiling Relative Inhibition Simultaneously in Mixtures indicated that the sialylation-related lncRNA signature could serve as a potential predictor for chemosensitivity. Collectively, this is the first sialylation lncRNA-based signature for predicting the prognosis, immune landscape, and chemotherapeutic response in CRC, and may provide vital guidance to facilitate risk stratification and optimize individualized therapy for CRC patients. |
| first_indexed | 2024-04-13T18:55:38Z |
| format | Article |
| id | doaj.art-9ac585e963d040758bbe8f8717ed7722 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T18:55:38Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9ac585e963d040758bbe8f8717ed77222022-12-22T02:34:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.994874994874Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancerMingxuan ZhouSilin LvYufang HouRixin ZhangWeiqi WangZheng YanTiegang LiWenqiang GanZifan ZengFang ZhangMin YangAberrant sialylation plays a key biological role in tumorigenesis and metastasis, including tumor cell survival and invasion, immune evasion, angiogenesis, and resistance to therapy. It has been proposed as a possible cancer biomarker and a potential therapeutic target of tumors. Nevertheless, the prognostic significance and biological features of sialylation-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remain unclear. This study aimed to develop a novel sialylation-related lncRNA signature to accurately evaluate the prognosis of patients with CRC and explore the potential molecular mechanisms of the sialylation-related lncRNAs. Here, we identified sialylation-related lncRNAs using the Pearson correlation analysis on The Cancer Genome Atlas (TCGA) dataset. Univariate and stepwise multivariable Cox analysis were used to establish a signature based on seven sialylation-related lncRNAs in the TCGA dataset, and the risk model was validated in the Gene Expression Omnibus dataset. Kaplan-Meier curve analysis revealed that CRC patients in the low-risk subgroup had a better survival outcome than those in the high-risk subgroup in the training set, testing set, and overall set. Multivariate analysis demonstrated that the sialylation-related lncRNA signature was an independent prognostic factor for overall survival, progression-free survival, and disease-specific survival prediction. The sialylation lncRNA signature-based nomogram exhibited a robust prognostic performance. Furthermore, enrichment analysis showed that cancer hallmarks and oncogenic signaling were enriched in the high-risk group, while inflammatory responses and immune-related pathways were enriched in the low-risk group. The comprehensive analysis suggested that low-risk patients had higher activity of immune response pathways, greater immune cell infiltration, and higher expression of immune stimulators. In addition, we determined the sialylation level in normal colonic cells and CRC cell lines by flow cytometry combined with immunofluorescence, and verified the expression levels of seven lncRNAs using real-time quantitative polymerase chain reaction. Finally, combined drug sensitivity analysis using the Genomics of Drug Sensitivity in Cancer, Cancer Therapeutics Response Portal, and Profiling Relative Inhibition Simultaneously in Mixtures indicated that the sialylation-related lncRNA signature could serve as a potential predictor for chemosensitivity. Collectively, this is the first sialylation lncRNA-based signature for predicting the prognosis, immune landscape, and chemotherapeutic response in CRC, and may provide vital guidance to facilitate risk stratification and optimize individualized therapy for CRC patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.994874/fullsialylationlong noncoding RNAcolorectal cancerprognostic signatureimmune microenvironment |
| spellingShingle | Mingxuan Zhou Silin Lv Yufang Hou Rixin Zhang Weiqi Wang Zheng Yan Tiegang Li Wenqiang Gan Zifan Zeng Fang Zhang Min Yang Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer Frontiers in Immunology sialylation long noncoding RNA colorectal cancer prognostic signature immune microenvironment |
| title | Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer |
| title_full | Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer |
| title_fullStr | Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer |
| title_full_unstemmed | Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer |
| title_short | Characterization of sialylation-related long noncoding RNAs to develop a novel signature for predicting prognosis, immune landscape, and chemotherapy response in colorectal cancer |
| title_sort | characterization of sialylation related long noncoding rnas to develop a novel signature for predicting prognosis immune landscape and chemotherapy response in colorectal cancer |
| topic | sialylation long noncoding RNA colorectal cancer prognostic signature immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.994874/full |
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