Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis

Abstract

BackgroundMore accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis.MethodsAn observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases. Long-term outcomes will be cancer-specific survival, recurrence-free survival and overall survival at 5 years from diagnosis. Beyond routine clinicopathological and anthropometric characteristics and laboratory and biochemistry results, the project allows for additional blood samples and fresh-frozen tumour and normal tissue for investigation of circulating tumour cells (CTCs) and novel biomarkers (e.g. immune cells, microRNAs etc.). Tumour specimens will be investigated by immunohistochemistry in full slides. Extracted DNA/RNA will be analysed for genomic markers using specific PCR techniques and next-generation sequencing (NGS) panels. Flow cytometry will be used to characterise biomarkers in blood. Collaboration is open and welcomed, with particular interest in mutual opportunities for validation studies.Status and perspectivesThe project is ongoing and recruiting at an expected rate of 120–150 patients per year, since January 2013. A project on circulating tumour cells (CTCs) has commenced, with analysis being prepared. Investigating molecular classes beyond the TNM staging is under way, including characteristics of microsatellite instability (MSI) and elevated microsatellite alterations in selected tetranucleotides (EMAST). Hot spot panels for known mutations in CRC are being investigated using NGS. Immune-cell characteristics are being performed by IHC and flow cytometry in tumour and peripheral blood samples. The project has ethical approval (REK Helse Vest, #2012/742), is financially supported with a Ph.D.-Grant (EMAST project; Folke Hermansen Cancer Fund) and a CTC-project (Norwegian Research Council; O. Nordgård). The ACROBATICC clinical and molecular biobank repository will serve as a long-term source for novel exploratory analysis and invite collaborators for mutual validation of promising biomarker results. The project aims to generate results that can help better discern prognostic groups in stage II/III cancers; explore prognostic and predictive biomarkers, and help detail the biology of colorectal liver metastasis for better patient selection and tailored treatment. The project is registered at http://www.ClinicalTrials.gov NCT01762813.

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

“…Patients with non-metastatic primary CRC were recruited from an ongoing prospective, clinical and molecular biomarker outcomes project for translational cancer research in resectable primary CRC and liver metastasis (19). All included patients provided written informed consent.…”

Discovery of core gene families associated with liver metastasis in colorectal cancer and regulatory roles in tumor cell immune infiltration

“…Nowadays, with the development of ‘big data’ and advancements in bioinformatics, analyzing large datasets has become faster, more thorough, and convenient. Large datasets such as screening of genomic markers of colorectal liver metastasis using next-generation sequencing (NGS) platforms are available publicly [26] . Differential expression analysis is effective in detecting the differentially expressed genes (DEGs) in various pathological groups.…”

Identification of Candidate Biomarkers in Malignant Ascites from Patients with Hepatocellular Carcinoma by iTRAQ-Based Quantitative Proteomic Analysis

“…Other than the widely used genomic analyses such as microarrays and NGS sequencing technologies in molecular biomarker discovery, proteomic-based approaches have shown many advantages in protein biomarkers screening [ 9 – 11 ]. Moreover, protein based studies can assist in systems biology research which could lead to identification of new drug targets [ 12 ].…”