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Research Article
Wenlin An
Beijing University of Chemical Technology
Corresponding Author
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Background: Small nuclear ribonucleoprotein polypeptide A (SNRPA1) is a splicing factor (SF) responsible for the processing of pre−mRNA into mRNA. The purpose of this study was to explore the clinicopathological characteristics and prognostic significance of SNRPA1 mRNA expression in liver cancer and its potential mechanism as an SF.
Methods: A total of 418 RNA−Seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Alternative splicing (AS) profiles were downloaded from TCGA SpliceSeq. Wilcoxon rank-sum tests were used to compare normal tissues with tumor tissues and analyze subgroups. We used the Kaplan−Meier analysis method to draw the survival curves. Univariate and multivariate Cox analyses were employed to estimate the prognostic value of SNRPA1. Gene set enrichment analysis (GSEA) was performed to identify the signaling pathways. Then we used univariate and Pearson's correlation tests to analyze the correlation between SFs and exon skip (ES) events. Wilcoxon rank-sum tests were applied to analyze the relationships between different spliceosome and cancers. We also analyzed the relationship between the expression of SCP2 (related to SNRPA1) and clinical symptoms. We then evaluated the expression levels of these genes with clinical samples and The Clinical Proteomic Tumor Analysis Consortium (CPTAC).
Results: The level of SNRPA1 mRNA expression in liver cancer was significantly up−regulated in tumor tissues compared with normal tissues (p = 1.411e−27) in liver cancer and was positively correlated with survival status (p = 0.035). In addition, we found that SNRPA1 mRNA levels can reflect the prognosis of liver cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 1.02–1.14, p = 0.005). The enriched KEGG pathway by GESA revealed a splicesome as the main pathway of SNRPA1. Alternative splicing events of SNRPA1 was related to the expression of SCP2. SNRPA1 exon 6 skip and SCP2 exon 12 skip correlated with many cancer types. Finally, SNRPA1 and SCP2 percent−spliced−in (PSI) values positively correlated with survival status (p = 3.022e−04 and p = 2.932e−03).
Conclusions: Splicing Factor SNRPA1 is superior to its mRNA expression in predicting the prognosis of liver cancer and correlates with the SCP2 spliceosome, which is consistent with that of SNRPA1 in clinical samples.
Keywords
SNRPA1, Liver cancer, Prognosis, Splicing factors, SCP2
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No competing interests reported.
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On 12 Oct, 2021
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Reviews received
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Reviewers agreed
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Reviewers invited
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This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Wenlin An
Beijing University of Chemical Technology
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 02 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 12 Oct, 2021
Reviews received
Received 03 Oct, 2021
Reviewers agreed
On 22 Sep, 2021
Reviews received
Received 23 Jun, 2021
Reviewers agreed
On 16 Jun, 2021
Reviewers invited
Invitations sent on 15 Jun, 2021
Editor assigned
On 15 Jun, 2021
Editor invited
On 31 May, 2021
Submission checks complete
On 31 May, 2021
First submitted
On 09 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Small nuclear ribonucleoprotein polypeptide A (SNRPA1) is a splicing factor (SF) responsible for the processing of pre−mRNA into mRNA. The purpose of this study was to explore the clinicopathological characteristics and prognostic significance of SNRPA1 mRNA expression in liver cancer and its potential mechanism as an SF.
Methods: A total of 418 RNA−Seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Alternative splicing (AS) profiles were downloaded from TCGA SpliceSeq. Wilcoxon rank-sum tests were used to compare normal tissues with tumor tissues and analyze subgroups. We used the Kaplan−Meier analysis method to draw the survival curves. Univariate and multivariate Cox analyses were employed to estimate the prognostic value of SNRPA1. Gene set enrichment analysis (GSEA) was performed to identify the signaling pathways. Then we used univariate and Pearson's correlation tests to analyze the correlation between SFs and exon skip (ES) events. Wilcoxon rank-sum tests were applied to analyze the relationships between different spliceosome and cancers. We also analyzed the relationship between the expression of SCP2 (related to SNRPA1) and clinical symptoms. We then evaluated the expression levels of these genes with clinical samples and The Clinical Proteomic Tumor Analysis Consortium (CPTAC).
Results: The level of SNRPA1 mRNA expression in liver cancer was significantly up−regulated in tumor tissues compared with normal tissues (p = 1.411e−27) in liver cancer and was positively correlated with survival status (p = 0.035). In addition, we found that SNRPA1 mRNA levels can reflect the prognosis of liver cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 1.02–1.14, p = 0.005). The enriched KEGG pathway by GESA revealed a splicesome as the main pathway of SNRPA1. Alternative splicing events of SNRPA1 was related to the expression of SCP2. SNRPA1 exon 6 skip and SCP2 exon 12 skip correlated with many cancer types. Finally, SNRPA1 and SCP2 percent−spliced−in (PSI) values positively correlated with survival status (p = 3.022e−04 and p = 2.932e−03).
Conclusions: Splicing Factor SNRPA1 is superior to its mRNA expression in predicting the prognosis of liver cancer and correlates with the SCP2 spliceosome, which is consistent with that of SNRPA1 in clinical samples.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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