Dataset Information

Characterization of biomarkers in Colorectal Cancer Liver Metastases as a prognostic tool

ABSTRACT: In this study we aimed to explore the molecular landscape of hepatic metastases and adjacent tissue in order to delineate a potential molecular signature that may be predictive for clinical benefit of CRCLM resection. Consecutive patients who underwent CRCLM resection between 2008 and 2015 at RMC, and for whom pathological specimen was available were included in the study. Cases were divided into two cohorts based on the interval between resection of liver metastases and disease recurrence- patients with less than 12-month interval were defined as ×´poor prognosis×´ (PP) and patients with more than 12 months as ×´good prognosis×´ (GP). Clinical data was retrieved from the medical records. Proteomic analysis was performed on the pathological bio specimen and correlated to demographics and clinical outcomes. Fifty-eight patients were included in the study. 29 in the GP cohort and 29 in the PP cohort. Proteomic analysis of the two-cohort revealed 99 proteins that were 38 differentially expressed, about a third of them associate with the extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Tamar Ziv

LAB HEAD: Irit Ben-Aharon

PROVIDER: PXD022613 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

Characterization of Biomarkers in Colorectal Cancer Liver Metastases as a Prognostic Tool.

Michal Sternschuss S Tal Goshen-Lago GL Gali Perl P Miki Goldenfeld G Elana Brook B Baroch Brenner B Hanoch Kashtan K Irit Ben Aharon BA Riad Haddad H

Journal of personalized medicine 20211021 11

<h4>Background</h4>Unfortunately, the majority of patients with colorectal cancer liver metastases (CRCLM) experience disease recurrence following hepatic surgery. The key challenge is therefore optimal patient selection, which currently relies on anatomical and clinical parameters. Exploring a potential molecular signature may be predictive for seeing a clinical benefit from CRCLM resection.<h4>Methods</h4>Consecutive patients who underwent CRCLM resection at our medical center between 2006 and ...[more]

PMID: 34834411

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Project description:Using Human WG CodeLink microarrays, we established the expression profiling of 26 LARC without metastasis to gain insight into the molecular signatures associated with response to treatment after CRT. The study initially included a total of 35 consecutive patients with locally advanced rectal cancer (LARC) treated at Virgen de las Nieves Hospital from 2008 until 2010. Written informed consent was obtained from all the patients, and the study protocol was approved by the local Clinical Research (Ethics) Committee. They were distributed in two subgroups following a histological classification of response to treatment. Pretherapeutic staging was performed, including complete medical history and physical evaluation, digital rectal examination, endorectal ultrasound, rigid rectoscopy, colonoscopy, PET/TC and chest x-ray. Tumor samples were prospectively obtained during the rectoscopy. All patients subsequently received a total dose of 50.4Gy of radiatio (28 fractions of 1.8Gy) associated with capecitabine or capecitabine and oxaliplatine. Standardized surgery was performed, including total mesorectal excision, after an interval of 8 weeks after chemoradiotherapy. Tumor response was assessed in surgical specimen by semi-quantitative pathological examination (regression grade) including UICC stage. Histopathological tumor regression was graded based on the semiquantitative 5 point tumor regression grading (TRG) system: TRG1 or a TRG2 scores were considered Responders, whereas TRG3, TRG4, and TRG5 scores were classified as Non-Responders. In addition, the tumor regression or radiotherapy effects were assessed by positron emission tomography (18F-FDG PET). Tumor samples of LARC were collected from 35 patients. Nine patients were finally excluded due to the poor quality of the RNA or contradictory results of MandardM-BM-4s criteria and histopathological downstaging, resulting a total of 26 patients. Complete clinical data regarding, age, sex, stage of disease, response to therapy, and overall survival from 26 patients (10 responders and 16 non-responders) was provided in the sample characteristics field. CRT: Chemoradiation; Cap: Capecitabine; Capox: Capecitabine and Oxaliplatine; cTN: clinical stage; Surg: surgical technique; LAR: Low anterior resection; APR: Abdmino-perineal resection; HART: Hartmann, TRG: Tumor Regression Grade; Downst: Downstaging; Downs: downsizing, Resp: response, CPR: complete pathologic response

Project description:Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility. Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research. Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.

Dataset Information

Characterization of biomarkers in Colorectal Cancer Liver Metastases as a prognostic tool

Publications

Characterization of Biomarkers in Colorectal Cancer Liver Metastases as a Prognostic Tool.

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