Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA343887 | ENA |
REPOSITORIES: ENA
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Project description:To understand the molecular mechanism of rectal cancer and develop markers for disease prognostication, we generated and explored a dataset from 243 rectal cancer patients by gene expression microarray analysis of cancer samples and matched controls, and SNP-arrays of germline DNA. We found that two of the loci most strongly linked with colorectal cancer (CRC) risk, 8q24 (upstream of MYC) and 18q21 (in the intron of SMAD7), as well as 20q13 (in the intron of LAMA5), are tightly associated with the prognosis of rectal cancer patients. For SNPs on 18q21 (rs12953717 and rs4464148) and 20q13 (rs4925386), alleles that correlate with higher risk for the development of CRC are associated with shorter disease free survival (DFS). However, for rs6983267 on 8q24, the low risk allele is associated with a higher risk for recurrence and metastasis after surgery, and importantly, is strongly correlated with the resistance of CRC cell lines to chemoradiotherapy (CRT). We also found that although MYC expression is dramatically increased in cancer, patients with higher levels of MYC have a better prognosis. The expression of SMAD7 is weakly correlated with DFS. Notably, the presence of the 8q24 and 18q21 SNP alleles is not correlated with expression levels of MYC and SMAD7. rs4464148, and probably rs6983267 and rs4925386, are linked with overall survival time of patients. In conclusion, we show that several CRC risk SNPs detect subpopulations of rectal cancer patients with poor prognosis, and that rs6983267 probably affects prognosis through interfering with the resistance of cancer cells to CRT.
2017-11-28 | GSE87211 | GEO
Project description:Unsupervised classification of gene expression profiles has resulted in the identification of biologically and clinically distinct colon cancer subtypes (CCSs). The subtype that associates with poor clinical outcome displays a mesenchymal gene expression profile. No driver mutation has been identified for this category and patients are heterogeneous with regard to commonly used clinical markers. Here we report a regulatory network consisting of the miR-200 family members that tunes the majority of genes differentially expressed in the poor prognosis CCS, including genes involved in the epithelial-mesenchymal transition (EMT) process. Our data indicate that the epigenetic silencing of the miR-200 family by promoter methylation is identifying the mesenchymal CCS and is predictive of disease-free survival in this malignancy. We demonstrate that the molecular features of poor prognosis colon cancer - expression of EMT-associated genes and miR-200 promoter methylation - can already be installed at the premalignant stage, suggesting a highly malignant potential of specific colon cancer precursor lesions. Four colorectal cancer cell lines that display methylated miR-200 loci have been used to overexpress miR-200 family members from both loci separatedly or simultaneously.
2015-09-01 | E-GEOD-65551 | biostudies-arrayexpress
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
Project description:We noticed that a recently identified poor prognosis stem/serrated molecular subtype of colorectal cancer (CRC) is characterized by up-regulation of transcripts known to be also expressed by stromal cells. To better define the origin of such transcripts, we analyzed RNAseq and microarray datasets from CRC mouse xenografts, where human cancer cells are supported by murine stroma. The analysis revealed that mRNA levels of stem/serrated subtype genes are mostly due to stromal expression, even when the stromal fraction is below 5%. Indeed, a classifier based on genes exclusively expressed by cancer-associated fibroblasts was significantly associated, in multiple datasets, to poor prognosis of CRC and to radioresistance of rectal cancer. Molecular Characterization of 72 primary rectal cancer formalin-fixed, paraffin-embedded (FFPE) specimens including 58 pretreatment specimens, 14 surgical specimens.
2014-05-01 | E-GEOD-56699 | biostudies-arrayexpress
Project description:BORIS expresses abnormally in colorectal cancer cells. Both the expression and the copy number of BORIS are remarkably higher in colorectal cancer cells than in normal colon or rectal cells. BORIS is potential diagnosis, prognosis or therapeutic target for colorectal cancer. To expand our view of the signaling pathway related with BORIS, altered gene expression by BORIS knockdown was assessed by microarray assay. To study the gene regulation by BORIS knockdown, microarray assay was applied to screen the gene expression regulated by BORIS siRNA in colorectal cancer cells HCT116 and Caco-2
2018-07-01 | GSE86172 | GEO
Project description:Neoadjuvant chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, there are no good predictive methods. This study investigated whether specific lncRNA expression is associated with response to CRT. Tissue biopsies were obtained from patients before CRT. LncRNA expression was analyzed using one-color microarrays technique comparing signatures between good respondersand poor responders, as measured by tumour regression grade (TRG).
2020-02-22 | GSE145666 | GEO
Project description:We noticed that a recently identified poor prognosis stem/serrated molecular subtype of colorectal cancer (CRC) is characterized by up-regulation of transcripts known to be also expressed by stromal cells. To better define the origin of such transcripts, we analyzed RNAseq and microarray datasets from CRC mouse xenografts, where human cancer cells are supported by murine stroma. The analysis revealed that mRNA levels of stem/serrated subtype genes are mostly due to stromal expression, even when the stromal fraction is below 5%. Indeed, a classifier based on genes exclusively expressed by cancer-associated fibroblasts was significantly associated, in multiple datasets, to poor prognosis of CRC and to radioresistance of rectal cancer. Tumor Matched with Corresponding PDX
2014-05-01 | E-GEOD-56695 | biostudies-arrayexpress
Project description:The rectal cancer patient data set consists of 10 patients from a clinical study at the Surgery department of the University Medical Center Göttingen collected over a longer time. Patients were chosen based on the follow-up time and development of a distant metastasis. First a balanced sample size of five versus five patients with and without a metastatic event was chosen. This needed to be changed to six versus four. Two conditions of rectal cancer patient data separates by the event of distant metastasis: 1. good prognosis, no event (4 samples), 2. bad prognosis, event (6 samples) Single-end sequencing on a Illumina HiSeq 200 machine with the standard total_RNA protocol with 50 base pairs read length was used
2018-05-23 | GSE99897 | GEO
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific “signature” associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer.
2012-04-25 | GSE29298 | 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.
2017-05-17 | GSE98959 | GEO