See the published version of this preprint at BMC Gastroenterology.
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Research article
Hongtao Jia
Tianjia Genomes Tech CO., LTD.
Corresponding Author
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Background: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC.
Methods: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods.
Result: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC=1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology.
Conclusions: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.
Keywords
Alternative splicing (AS), colorectal cancer (CRC), metastasis, RNA-seq, TCGA
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CURRENT STATUS: Published
View the published article at BMC Gastroenterology.
Version 5
Posted 13 May, 2020
No community comments so far
Editorial decision: Accept
On 30 Apr, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
No comments provided
Submission checks complete
On 24 Apr, 2020
Editorial decision: Minor revision
On 24 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 22 Apr, 2020
Reviewers invited
Invitations sent on 10 Feb, 2020
Editor assigned
On 11 Dec, 2019
Submission checks complete
On 10 Dec, 2019
Editor invited
On 10 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 24 Nov, 2019
Review #1 received
Received 11 Nov, 2019
Reviewer #1 agreed
On 30 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Editor assigned
On 23 Oct, 2019
Submission checks complete
On 22 Oct, 2019
Editor invited
On 22 Oct, 2019
No comments provided
Editorial decision: Major revision
On 31 Aug, 2019
Review #2 received
Received 28 Aug, 2019
Reviewer #2 agreed
On 14 Aug, 2019
Reviewer #1 agreed
On 15 Jul, 2019
Review #1 received
Received 15 Jul, 2019
Editor assigned
On 14 Jul, 2019
Reviewers invited
Invitations sent on 14 Jul, 2019
Submission checks complete
On 25 Jun, 2019
Editor invited
On 25 Jun, 2019
First submitted
On 06 Jun, 2019
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See the published version of this preprint at BMC Gastroenterology.
This is a preprint, 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
Hongtao Jia
Tianjia Genomes Tech CO., LTD.
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: Published
View the published article at BMC Gastroenterology.
Version 5
Posted 13 May, 2020
No community comments so far
Editorial decision: Accept
On 30 Apr, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
No comments provided
Submission checks complete
On 24 Apr, 2020
Editorial decision: Minor revision
On 24 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 22 Apr, 2020
Reviewers invited
Invitations sent on 10 Feb, 2020
Editor assigned
On 11 Dec, 2019
Submission checks complete
On 10 Dec, 2019
Editor invited
On 10 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 24 Nov, 2019
Review #1 received
Received 11 Nov, 2019
Reviewer #1 agreed
On 30 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Editor assigned
On 23 Oct, 2019
Submission checks complete
On 22 Oct, 2019
Editor invited
On 22 Oct, 2019
No comments provided
Editorial decision: Major revision
On 31 Aug, 2019
Review #2 received
Received 28 Aug, 2019
Reviewer #2 agreed
On 14 Aug, 2019
Reviewer #1 agreed
On 15 Jul, 2019
Review #1 received
Received 15 Jul, 2019
Editor assigned
On 14 Jul, 2019
Reviewers invited
Invitations sent on 14 Jul, 2019
Submission checks complete
On 25 Jun, 2019
Editor invited
On 25 Jun, 2019
First submitted
On 06 Jun, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Gastroenterology.
Background: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC.
Methods: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods.
Result: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC=1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology.
Conclusions: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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