Integrative computational biology and molecular determinants of rectal cancer resistance to chemoradiotherapies
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45404 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA193688
REPOSITORIES: GEO
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2020-08-01 | GSE119409 | GEO
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2022-12-23 | GSE216024 | GEO
Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen. 29 gastric adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control samples, 29 colorectal adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control, 27 small bowel adenocarcinomas done on 30K oligonucleotide arrays of which 2 samples are also done on 5K BAC arrays as control.
2011-06-13 | E-GEOD-23418 | biostudies-arrayexpress
Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen.
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2017-01-11 | GSE93375 | GEO
Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.
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Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. Colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures to predict response to bevacizumab, gene expression profiles were compared between Reponder and Non-responder.
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