| 1. |
- Hases, Linnea, et al.
(author)
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The importance of sex in colorectal cancer biomarker discovery
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Other publication (other academic/artistic)abstract
- Colorectal cancer (CRC) is the third leading cause for cancer deaths, indicating the needfor new diagnostic and prognostic biomarkers. The advances in omics technologies andbioinformatics can speed up and improve current biomarker discovery strategies.Machine learning has been integrated for analysis of transcriptomic data for severalcancers. However, in addition to improved data-analysis, there is a need to investigate theimpact of sex in the biomarker discovery since there are several sex-differences in theincidence, mortality, prognosis and tumor characteristics of CRC. First we investigated ifthere are any sex-differences in the transcriptome of normal colon and CRC andinvestigated if there are any sex-differences in the differentially expressed genes betweenpaired-normal and CRC. In an attempt to study sex-specific biomarkers we used TCGAdata and performed feature selection with Vita, Boruta and MRMR in combination withmachine learning to identify top CRC biomarkers. Interestingly, we found stronger sexdifferencesin the normal colon compared to in CRC. Although the sex-differences werestronger in normal colon, sex showed to have a significant impact of the prognostic valueof the biomarkers. 13 of the selected features showed a sex-specific prognostic value. Thepreviously proposed prognostic biomarkers ESM1 and GUCA2A showed a male-specificprognostic value whereas CLDN1 was specific for females. Additionally, we found somenovel prognostic biomarkers including TSPAN7 (females), SLC25A23 (females) andC2orf88 (males). In conclusion, our data show the importance of sex in the discovery ofCRC biomarkers and proposes 13 sex-specific CRC prognostic biomarkers.
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| 2. |
- Hases, Linnea, et al.
(author)
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The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:3
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is the third leading cause of cancer deaths. Advances within bioinformatics, such as machine learning, can improve biomarker discovery and ultimately improve CRC survival rates. There are clear sex differences in CRC characteristics, but the impact of sex has not been considered with regards to CRC biomarkers. Our aim here was to investigate sex differences in the transcriptome of a normal colon and CRC, and between paired normal and tumor tissue. Next, we attempted to identify CRC diagnostic and prognostic biomarkers and investigate if they are sex-specific. We collected paired normal and tumor tissue, performed RNA-seq, and applied feature selection in combination with machine learning to identify the top CRC diagnostic biomarkers. We used The Cancer Genome Atlas (TCGA) data to identify sex-specific CRC diagnostic biomarkers and performed an overall survival analysis to identify sex-specific prognostic biomarkers. We found transcriptomic sex differences in both the normal colon tissue and in CRC. Forty-four of the top-ranked biomarkers were sex-specific and 20 biomarkers showed a sex-specific prognostic value. Our data show the importance of sex in the discovery of CRC biomarkers. We propose 20 sex-specific CRC prognostic biomarkers, including ESM1, GUCA2A, and VWA2 for males and CLDN1 and FUT1 for females.
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