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pmid:35885025

Integrated Bioinformatics Analysis of the Hub Genes Involved in Irinotecan Resistance in Colorectal Cancer.

Jakub Kryczka · Joanna Boncela

Biomedicines · 2022 doi:10.3390/biomedicines10071720

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Integrated Bioinformatics Analysis of the Hub Genes Involved in Irinotecan Resistance in Colorectal Cancer.
doi
10.3390/biomedicines10071720
pmid
35885025
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[0]
Jakub Kryczka
[1]
Joanna Boncela
journal
Biomedicines
year
2022
abstract
Different drug combinations including irinotecan remain some of the most important therapeutic modalities in treating colorectal cancer (CRC). However, chemotherapy often leads to the acquisition of cancer drug resistance. To bridge the gap between in vitro and in vivo models, we compared the mRNA expression profiles of CRC cell lines (HT29, HTC116, and LoVo and their respective irinotecan-resistant variants) with patient samples to select new candidate genes for the validation of irinotecan resistance. Data were downloaded from the Gene Expression Omnibus (GEO) (GSE42387, GSE62080, and GSE18105) and the Human Protein Atlas databases and were subjected to an integrated bioinformatics analysis. The protein-protein interaction (PPI) network of differently expressed genes (DEGs) between FOLFIRI-resistant and -sensitive CRC patients delivered several potential irinotecan resistance markers: NDUFA2, SDHD, LSM5, DCAF4, COX10 RBM8A, TIMP1, QKI, TGOLN2, and PTGS2. The chosen DEGs were used to validate irinotecan-resistant cell line models, proving their substantial phylogenetic heterogeneity. These results indicated that in vitro models are highly limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly utilized to analyze specific mechanisms on their molecular levels but cannot mirror the complicated drug resistance network observed in patients.
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Differently expressed genes (DEGs) were further calculated and visualized with JASP 0.14.1.0 software (https://jasp-stats.org/ (accessed on 18 May 2022)) using a normality test (Shapiro–Wilk’s), followed by a Mann–Whitney U test (for not normally distributed data) or T-test (for normally distributed data).
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sections[3] "2.1. Microarray Data Processing and Analysis" paragraph 2
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Differently expressed genes (DEGs) were further calculated and visualized with JASP 0.14.1.0 software (https://jasp-stats.org/ (accessed on 18 May 2022)) using a normality test (Shapiro–Wilk’s), followed by a Mann–Whitney U test (for not normally distributed data) or T-test (for normally distributed data).
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Stage II and stage III colorectal cancer
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Differently expressed genes (DEGs) were further calculated and visualized with JASP 0.14.1.0 software (https://jasp-stats.org/ (accessed on 18 May 2022)) using a normality test (Shapiro–Wilk’s), followed by a Mann–Whitney U test (for not normally distributed data) or T-test (for normally distributed data).
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ance. To bridge the gap between in vitro and in vivo models, we compared the mRNA expression prof
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limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can
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and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly util
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version). The GSE62080 database comprised 21 patients with advanced colorectal cancer treated using the
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2. Materials and Methods 2.1. Microarray Data Processing and Analysis Gene Expression
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a GPL16297 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F platform (Agilent Systematic Na
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rom different stages. One hundred and eleven microarray datasets (77 for LCM samples and 17 pairs fo
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Complete file
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To bridge the gap between in vitro and in vivo models, we compared the mRNA expression profiles of CRC cell lines (HT29, HTC116, and LoVo and their respective irinotecan-resistant variants) with patient samples to select new candidate genes for the validation of irinotecan resistance. Data were downloaded from the Gene Expression Omnibus (GEO) (GSE42387, GSE62080, and GSE18105) and the Human Protein Atlas databases and were subjected to an integrated bioinformatics analysis. The protein-protein interaction (PPI) network of differently expressed genes (DEGs) between FOLFIRI-resistant and -sensitive CRC patients delivered several potential irinotecan resistance markers: NDUFA2, SDHD, LSM5, DCAF4, COX10 RBM8A, TIMP1, QKI, TGOLN2, and PTGS2. The chosen DEGs were used to validate irinotecan-resistant cell line models, proving their substantial phylogenetic heterogeneity. These results indicated that in vitro models are highly limited and favor different mechanisms than in vivo, patient-derived ones. Thus, cell lines can be perfectly utilized to analyze specific mechanisms on their molecular levels but cannot mirror the complicated drug resistance network observed in patients.", "claims": [{"id": "claim-method", "statement": "Differently expressed genes (DEGs) were further calculated and visualized with JASP 0.14.1.0 software (https://jasp-stats.org/ (accessed on 18 May 2022)) using a normality test (Shapiro–Wilk’s), followed by a Mann–Whitney U test (for not normally distributed data) or T-test (for normally distributed data).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35885025", "locator": "sections[3] \"2.1. 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"sample_accessions": ["GSM1519418", "GSM1519419", "GSM1519420", "GSM1519421", "GSM1519422", "GSM1519423", "GSM1519424", "GSM1519425", "GSM1519426", "GSM1519427", "GSM1519428", "GSM1519429", "GSM1519430", "GSM1519431", "GSM1519432", "GSM1519433", "GSM1519434", "GSM1519435", "GSM1519436", "GSM1519437", "GSM1519438"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE18105 not downloaded", "asset:data:geo:GSE18105 licence not read", "asset:data:geo:GSE42387 not downloaded", "asset:data:geo:GSE42387 licence not read", "asset:data:geo:GSE62080 not downloaded", 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