Project description:There are ~1.4 million cases of colorectal cancer (CRC) annually worldwide. Due to recent implementation of bowel cancer screening (BCS), incidence of diagnosis with stage I (T1/2, N0, M0) CRC has increased nearly four-fold; from approximately 12% pre-screening to approximately 42-45%. While survival rates for patients diagnosed with stage I CRC remains above 95%, and identification of patients at this early stage provides the best opportunity to improve in cancer survival rates, recent data has provided quantitative evidence that metastatic seeding can occur from disseminated cells at the very earliest stage of CRC development. The aim of study was to give an insight into aggressive “born-to-be-bad” biology through generation and transcriptional profiling of a novel case-controlled retrospective T1 CRC discovery cohort. We performed transcriptional and histological profiling to identify molecular pathology features of the high-risk metastatic phenotypes, discriminating between relapse and non-relapse T1 lesions and found that a cohort of aggressive early disseminating stage 1 CRC is associated with high cell intrinsic TGFB signalling and not stromal signalling.
Project description:If we can more accurately predict the likelihood of regional lymph node metastasis (LNM) for endoscopically resected T1-stage colorectal cancers (CRC), the number of unnecessary additional surgeries can be reduced. We aimed of identify miRNA markers that can predict LNM-positive tumors among T1-stage CRCs and we also developed a miRNA classifier set for facilitating the accuracy and applicability.
Project description:Characterization of gene expression profiles of primary human patient-derived T1 colorectal cancer-associated fibroblasts (T1CAFs) and patient-matched normal fibroblasts (NFs) by bulk RNA sequencing
Project description:Expression data derived from this analysis was used for transcriptional subtyping and to compare expression features of genomic subgroups In this dataset, we include the expression data obtained from 113 stage Ta and 104 stage T1 bladder tumours
Project description:Surgical resection of colorectal cancers (CRC) that have not invaded beyond the bowel wall (i.e. Stage I) can achieve 5-year patient survival rates exceeding 90%. In the majority of Stage I cases with T1 (submucosal) or T2 (not beyond the muscularis propria) depth of tumour invasion, surgery alone is curative. However, for approximately 10% of resected T1/2 CRC, even though histopathology inspection of the tumour deems it to be restricted to the bowel wall, malignant cells are identified in draining lymph nodes, signifying local metastasis. These patients are classified with Stage IIIA disease and are at greater risk than Stage I patients whose tumours show similar invasive depth, but lack lymph node involvement. To counter the risk of distant malignant dissemination, Stage IIIA patients require more extensive treatment with adjuvant chemotherapy, while Stage I patients do not. In this study we aim to get a better understanding of the underlying biological pathways linked to lymph node metastasis (LNM) using discovery based MS (DIA) and RNASeq as well as IHC and PRM to verify possible protein marker. All of this was done on archival tissue samples (FFPE).
Project description:In this study, we validated 992 previously identified differentially methylated regions (DMRs) in colorectal precancerous lesions compared to adjacent normal mucosa in a new series of 59 prospectively collected lesions and matched normal tissue using targeted bisulfite sequencing. Strong differences in methylation level were observed across the full set of validated DMRs. Based on the mean methylation levels of a panel of 30 selected DMRs tumors could be accurately classified. We thus provide a large list of validated DNA markers to be exploited in the development of noninvasive, colorectal tumor screening assays.
Project description:The introduction of bowel cancer screening has led to a significant increase in the proportion of patients being diagnosed with asymptomatic, early-stage colorectal cancer (CRC). Although the majority of these patients are successfully treated with surgery alone, a small proportion of patients have ‘born-to-be-bad’ aggressive lesions with early dissemination leading to distant metastases. Current standard of care histological assessment is unable to distinguish between these aggressive versus non-aggressive early lesions which is essential to provide appropriate clinical management decisions. This study aims to carry out molecular and histological profiling of approximately 300 T1 CRCs in order to develop a molecular stratifier based on the risk of relapse in early-invasive CRC. This novel T1 cohort will represent the world’s largest molecularly characterised T1 cohort of samples, with digital pathology assessment alongside whole exome sequencing, copy number variation analysis and 3’ RNA-seq. This data will be used to generate a robust panel of molecular and/or histological markers applicable to formalin-fixed paraffin embedded (FFPE) archival tissue which discriminates between T1 lesions based on risk of relapse, which will ultimately be used to inform clinical management of CRC at the earliest stages of the disease.