Project description:The treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified.
Project description:The treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified. Total RNAs were isolated from primary rectal tumor tissues of 69 patients who underwent chemoradiation therapy (CRT). These patients are classified into four different CRT responses: minimal response (MI), moderate response (MO), near total response (NT) and total response (TO). All the RNAs were subjected to microarray analysis using Affymetrix GenChip arrays.
Project description:To measure global gene expression in primary locally advanced rectal cancer patients who have undergone CRT and screen valuable biomarkers to predict the effects of CRT.Samples fromprimary locally advanced rectal cancer patients were collected. The effects of chemoradiotherapy were evaluated.
Project description:The purpose of this project was to find key long non-coding RNAs and mRNAs in rectal adenocarcinoma. RNA-sequencing was performed to identify the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in rectal adenocarcinoma compared to normal tissue.
Project description:Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. Here, we performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies carefully selected and collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between cases with complete (pCR) and incomplete response to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome Database and Plasma and Proteome Database). Seventeen potentially secreted candidates (pCR=1, pIR=13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC. The potential secreted biomarkers were also confirmed as associated with the nCRT response (GSE68204). These putative proteins are candidates to be assessed in liquid biopsies aiming a personalized treatment in LARC patients.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses.
Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patients’ survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify miRNA markers for ESCC CRT-response prediction through miRNA expression analyses. MiRNA expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery using Agilent human miRNA microarrays based on miRBase (release 18.0) GeneChip®.
Project description:Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. Specimens from 46 rectal cancer patients who approved to receive preoperative chemoradiotherapy were studied. We prospectively collected biopsy specimens during colonoscopic examination from rectal cancer before starting preoperative chemoradiotherapy. Specimens from tumors were snap-frozen in liquid nitrogen and stored at -80 C until use. Paralleled tumor specimens were formalin fixed and paraffin embedded for histologic examination and other specimens were used for RNA extraction. RNA was extracted from tumor tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. All patients received a total dose of 50.4 Gy of radiation, UFT(300-500mg/day) and LV (75mg/day) and underwent standardized curative resection, following an interval of 4 weeks after chemoradiotherapy.
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.