Project description:Purpose: MicroRNAs play a prominent role in a variety of physiological and pathological biological processes, including cancer. For rectal cancers, only limited data are available on microRNA expression profiles, while the underlying genomic and transcriptomic aberrations have been firmly established. We therefore aimed to comprehensively map the microRNA expression patterns of this disease. Experimental design: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 72 patients (68 tumors and 70 normal mucosa) with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa microRNA expression profiles were subsequently established for all patients. The expression of selected microRNAs was validated using semi-quantitative real-time PCR. Results: Forty-nine microRNAs were significantly differentially expressed (log2-fold difference >0.5 and P<0.001) between rectal cancer and normal rectal mucosa. The predicted targets for the identified microRNAs were enriched for the following KEGG pathways: Wnt, TGF-beta, mTOR, insulin, MAPK, and ErbB signaling. Between rectal tumor and normal tissue, miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652*, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p were found to be differentially expressed. Of clinical impact, miR-135b expression correlated significantly with overall survival that could be validated in a larger multicenter patient set (n=94). Conclusion: The comprehensive analysis of the rectal cancer microRNAome uncovered novel microRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of rectal cancer. The identification and validation of miR-135b will help to identify novel molecular targets and pathways for therapeutic exploitation.
Project description:Purpose: MicroRNAs play a prominent role in a variety of physiological and pathological biological processes, including cancer. For rectal cancers, only limited data are available on microRNA expression profiles, while the underlying genomic and transcriptomic aberrations have been firmly established. We therefore aimed to comprehensively map the microRNA expression patterns of this disease. Experimental design: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 72 patients (68 tumors and 70 normal mucosa) with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa microRNA expression profiles were subsequently established for all patients. The expression of selected microRNAs was validated using semi-quantitative real-time PCR. Results: Forty-nine microRNAs were significantly differentially expressed (log2-fold difference >0.5 and P<0.001) between rectal cancer and normal rectal mucosa. The predicted targets for the identified microRNAs were enriched for the following KEGG pathways: Wnt, TGF-beta, mTOR, insulin, MAPK, and ErbB signaling. Between rectal tumor and normal tissue, miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652*, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p were found to be differentially expressed. Of clinical impact, miR-135b expression correlated significantly with overall survival that could be validated in a larger multicenter patient set (n=94). Conclusion: The comprehensive analysis of the rectal cancer microRNAome uncovered novel microRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of rectal cancer. The identification and validation of miR-135b will help to identify novel molecular targets and pathways for therapeutic exploitation. Paired samples from rectal tumor and matched normal samples. Included are also 2 technical replicates.
Project description:Stromal and extracellular matrix related genes are downregulated in KRAS mutant rectal adenocarcinoma We used Affymetrix U133 platform to profile the differences in the transcriptome of KRAS-wild-type and KRAS-mutant rectal cancer specimens
Project description:Biopsy specimens were collected from rectal cancer before starting preoperative radiotherapy.The expression profiles were determined using Affymetrix Human Genome U95 version 2 arrays.Comparison between the sample groups allow to identify a set of discriminating genes that can be used for characterization of responders and nonresponders to preoperative radiotherapy in rectal cancer. Keywords: repeat
Project description:Unique sub-clones within rectal tumors may harbor mutations which contribute to inter-patient variation in response to neoadjuvant chemoradiotherapy (nCRT). Analysis of the influence of nCRT on the extent and nature of intra-tumoral genetic heterogeneity in rectal cancer may provide insights into mechanisms of resistance. Ten locally advanced rectal cancer patients underwent pre-treatment biopsies. At the time of surgery, tissue from the treated tumor was obtained and analyzed. Pre- and post-treatment specimens were subjected to whole exome and confirmatory deep sequencing for somatic mutations. Copy number variation was assessed using OncoScan SNP arrays. In total, data from 32 pre/post-treatment samples are provided. The provided data include the pre/post tumor samples and the Affymetrix OncoScan SNP arrays.
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.
Project description:DNA methylation was suggested as the promising biomarker for rectal cancer diagnosis. However, it remains a great challenge to search for the optimal methylation biomarkers to obtain ideal diagnostic performance. We aimed to identify new molecular markers for rectal cancer by evaluating their epigenomic and transcriptomic profiles. Genome-wide methylation analysis revealed 18568 probes with significant methylation differences between the six rectal cancer and paired normal samples. Transcriptome profiling presented 773 low-expressed and 1,161 over-expressed genes. After merging the DNA methylation with gene expression data, we identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels. A genome-wide DNA methylation approach merged with array-based gene expression profiles allowed identifying a number of novel, epigenetically regulated candidate tumor-related genes in rectal carcinogenesis, which can be a good strategy to discover optimal DNA methylation diagnostic panels.