Project description:In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC).
Project description:To measure global gene expression in primary metastatic colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. Samples from primary metastatic colorectal cancer patients were collected. The effects of chemotherapy were evaluated.
Project description:Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumour infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T cell infiltration in CLM using T cell receptor (TCR) repertoire sequencing. Eighty-five resected CLM from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T cell fractions were calculated, repertoire clonality was analysed based on Hill evenness curves, and TCR sequential convergence was assessed using network analysis.
Increased T cell fractions (10.6% vs 6.3%) were detected in CLM exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT exposed tumours independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence.
TCR repertoire sequencing can be used to quantify T cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T cell clonal expansion in CLM in a clinical context.
Project description:The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 39 patients with metastatic colorectal carcinoma
Project description:We carried out comprehensive analysis for the miRNA profiling of primary tumor and metastatic lesion which seems to be source of circulating miRNA. We picked up two patients who treated with primary tumor resection initially and received chemotherapy followed by surgical resection of liver metastasis. The total miRNA was isolated from frozen tissue specimens. SurePrint G3 Human miRNA microarray kit Rel.21.0 (Agilent Technologies) contains 2549 human microRNA probes. As previously reported, hsa-miR200c revealed specifically high expression in metastatic sites at both two cases. In two colorectal cancer patients, the frozen primary tumor, normal mucosa and liver-metastatic lesion were analyzed by microRNA microarray.
Project description:Using whole genome tumor gene expression profiling in patients treated for metastatic colorectal cancer, we attempted to define a signature able to discriminate between responders and non-responders to first-line chemotherapy.
Project description:To characterize metastatic progression of colorectal cancer, we performed mass spectrometry-based proteome analysis using large clinical cohort samples.
Project description:The objective is to generate a robust and validated predictor profile for chemotherapy response in patients with mCRC using microarray gene expression profiles of primary colorectal cancer tissue. To define a gene signature of response to chemotherapy in metastatic colorectal cancer, samples were obtained from 40 patients from Marques de Valdecilla Hospital who underwent primary surgery. Gene expression was detected and quantified using the Human Whole Genome U133 Plus 2.0 array (Affymetrix), containing 54675 human gene probes. Adequate RNA and microarray analysis were obtained from only 37 patients.
Project description:we aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild type colorectal cancer cells for suggesting novel treatment targets.