Survival-associated alternative splicing signatures in non-small cell lung cancer

Zhao, Delong; Zhang, Chuantao; Jiang, Man; Wang, Yongjie; Yu, Liang; Wang, Li; Qin, Kang; Rehman, Faisal

doi:10.18632/aging.102983

Cited by 27 publications

(22 citation statements)

References 32 publications

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“…Alternative splicing (AS) took place in human genes quite commonly ( Wang et al, 2008 ) and was critically associated with the carcinogenic process ( Zhao et al, 2020 ) during which splicing factors (SFs) play key roles. Dysregulating the network built by SFs and alternative splicing events (ASEs), the aberrant AS for some genes and somatic mutations of SFs have been reported that they would cause epithelial–mesenchymal transition and might modulate malignant transformation of cells ( Sveen et al, 2016 ; Kouyama et al, 2019 ; Wu et al, 2019 ; Xing et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer

Huang

Guo

Yan

et al. 2020

Front. Cell Dev. Biol.

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Background Breast cancer (BRCA) ranks among the top most common female malignancies and was regarded as incurable when combined with bone and distant metastasis. Alternative splicing events (ASEs) together with splicing factors (SFs) were considered responsible for the development and progression of tumors. Methods Datasets including RNA sequencing and ASEs of BRCA samples were achieved from TCGA and TCGASpliceSeq databases. Then, a survival model was built including 15 overall-survival-associated splicing events (OS-SEs) by Cox regression and Lasso regression. The co-expressed SFs of each bone-and-distant-metastasis-related OS-SE were discovered by Pearson correlation analysis. Additionally, Gene Set Variation Analysis (GSVA) was performed to identify the downstream mechanisms of the key OS-SEs. Finally, the results were validated in different online platforms. Results A reliable survival model was established (the area under ROC = 0.856), and CIRBP was found co-expressed with FAM110B ( R = 0.320, P < 0.001) associated with the fatty acid metabolism pathway. Conclusion Aberrant SF, CIRBP, regulated a specific ASE, exon skip (ES) of FAM110B, during which the fatty acid metabolism pathway played an essential part in tumorigenesis and prognosis of BRCA.

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Section: Introductionmentioning

confidence: 99%

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer

Huang

Guo

Yan

et al. 2020

Front. Cell Dev. Biol.

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“…AS, as a post-transcriptional regulatory process that modifies more than 90% of human genes, plays a significant role in enhancing the diversity of transcription and protein (9,12,13). In recent years, the dysregulation of AS has been found to be associated with the occurrence and development of a variety of cancers including NSCLC (26)(27)(28)(29)(30)(31)(32). For instance, Li et al profiled the genome-wide AS events of NSCLC from TCGA and constructed prognostic predictors for LUAD, LUSC and merged NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Although these prediction models showed a high predictive performance, the potential mechanism of the relationship between AS events and NSCLC has not been deeply discussed (26). In addition, Zhao et al carried out an AS analysis in NSCLC from the perspective of different sexes and subtypes, and prognostic models and SF-AS network were constructed to reveal the mechanism of AS events affecting the prognosis of NSCLC (32). However, there are few systematic works have been devoted to investigate the role of AS events in LUSC specifically.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the prognostic model for LUSC constructed by Li et al included more than 30 AS events, though those predictors showed a high predictive performance (26). And in the AS analysis performed by Zhao et al, the LUAD and LUSC cohorts were divided into two groups by sex, but the 1 year AUC value of ROC curve in LUSC_MALE group was only 0.752 (32). Furthermore, the risk score in the present model was found to be an independent prognostic factor for LUSC patients, further confirming the accuracy and clinical applicability of the model.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, cancer-specific AS events have been identified by comparing cancer tissues with normal controls in several studies. And associations between AS signatures and overall survival (OS) time of patients have been systematically evaluated in a variety of cancers, such as colorectal cancer, ovarian cancer, breast cancer, kidney renal clear cell carcinoma, esophageal carcinoma as well as NSCLC (26)(27)(28)(29)(30)(31)(32). However, although systematic analysis and prognostic prediction models of AS events for NSCLC have been conducted in some studies, no comprehensive study specifically for LUSC has been performed.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Survival-Associated Alternative Splicing Signatures in Lung Squamous Cell Carcinoma

Liu

Jia

et al. 2020

Front. Oncol.

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Purpose: Alternative splicing (AS) is a post-transcriptional process that plays a significant role in enhancing the diversity of transcription and protein. Accumulating evidences have demonstrated that dysregulation of AS is associated with oncogenic processes. However, AS signature specifically in lung squamous cell carcinoma (LUSC) remains unknown. This study aimed to evaluate the prognostic values of AS events in LUSC patients. Methods: The RNA-seq data, AS events data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was performed to identify survival-related AS events and survival-related parent genes were subjected to Gene Ontology enrichment analysis and gene network analysis. The least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression analysis were used to construct prognostic prediction models, and their predictive values were assessed by Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. Then a nomogram was established to predict the survival of LUSC patients. And the interaction network of splicing factors (SFs) and survival-related AS events was constructed by Spearman correlation analysis and visualized by Cytoscape. Results: Totally, 467 LUSC patients were included in this study and 1,991 survival-related AS events within 1,433 genes were identified. SMAD4, FOS, POLR2L, and RNPS1 were the hub genes in the gene interaction network. Eight prognostic prediction models (seven types of AS and all AS) were constructed and all exhibited high efficiency in distinguishing good or poor survival of LUSC patients. The final integrated prediction model including all types of AS events exhibited the best prognostic power with the maximum AUC values of 0.778, 0.816, 0.814 in 1, 3, 5 years ROC curves, respectively. Meanwhile, the nomogram performed well in predicting the 1-, 3-, and 5-year survival of LUSC patients. In addition, the SF-AS regulatory network uncovered a significant correlation between SFs and survival-related AS events. Conclusion: This is the first comprehensive study to analyze the role of AS events in LUSC specifically, which improves our understanding of the prognostic value of survival-related AS events for LUSC. And these survival-related AS events might serve as novel prognostic biomarkers and drug therapeutic targets for LUSC.

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Novel prognostic alternative splicing events in colorectal Cancer: Impact on immune infiltration and therapy response

Xiao,

Gao,

Zhao

et al. 2024

International Immunopharmacology

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Survival-associated alternative splicing signatures in non-small cell lung cancer

Cited by 27 publications

References 32 publications

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer

The Construction of Bone Metastasis-Specific Prognostic Model and Co-expressed Network of Alternative Splicing in Breast Cancer

Identification of Survival-Associated Alternative Splicing Signatures in Lung Squamous Cell Carcinoma

Novel prognostic alternative splicing events in colorectal Cancer: Impact on immune infiltration and therapy response

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