Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer
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.
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Posted 13 May, 2020
On 29 Apr, 2020
On 28 Apr, 2020
On 24 Apr, 2020
On 24 Apr, 2020
On 22 Apr, 2020
Invitations sent on 10 Feb, 2020
On 11 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
On 24 Nov, 2019
Received 11 Nov, 2019
On 30 Oct, 2019
Invitations sent on 29 Oct, 2019
On 23 Oct, 2019
On 22 Oct, 2019
On 22 Oct, 2019
On 31 Aug, 2019
Received 28 Aug, 2019
On 14 Aug, 2019
On 15 Jul, 2019
Received 15 Jul, 2019
On 14 Jul, 2019
Invitations sent on 14 Jul, 2019
On 25 Jun, 2019
On 25 Jun, 2019
On 06 Jun, 2019
Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer
Posted 13 May, 2020
On 29 Apr, 2020
On 28 Apr, 2020
On 24 Apr, 2020
On 24 Apr, 2020
On 22 Apr, 2020
Invitations sent on 10 Feb, 2020
On 11 Dec, 2019
On 10 Dec, 2019
On 10 Dec, 2019
On 24 Nov, 2019
Received 11 Nov, 2019
On 30 Oct, 2019
Invitations sent on 29 Oct, 2019
On 23 Oct, 2019
On 22 Oct, 2019
On 22 Oct, 2019
On 31 Aug, 2019
Received 28 Aug, 2019
On 14 Aug, 2019
On 15 Jul, 2019
Received 15 Jul, 2019
On 14 Jul, 2019
Invitations sent on 14 Jul, 2019
On 25 Jun, 2019
On 25 Jun, 2019
On 06 Jun, 2019
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