Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case-Control Study.

Unlabelled: Current morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.

High expression of secretory leukocyte protease inhibitor (SLPI) in stage III micro-satellite stable colorectal cancer is associated with reduced disease recurrence.

Secretory leukocyte protease inhibitor (SLPI) is a pleiotropic protein produced by healthy intestinal epithelial cells. SLPI regulates NF-κB activation, inhibits neutrophil proteases and has broad antimicrobial activity. Recently, increased SLPI expression was found in various types of carcinomas and was suggested to increase their metastatic potential.

Genetic Profiling of Colorectal Carcinomas of Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal cancer (CRC) compared to patients with IBD only. The aim of this study was to perform an extensive screen of known carcinogenic genomic alterations in patients with PSC-IBD, and to investigate whether such changes occur already in nondysplastic mucosa.

Methods: Archival cancer tissue and nondysplastic mucosa from resection specimens of 19 patients with PSC-IBD-CRC were characterized, determining DNA copy-number variations, microsatellite instability (MSI), mutations on 48 cancer genes, and CpG island methylator phenotype (CIMP).

Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases.

Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS).

Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer.

Aim: Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometry-based proteomics.

Patient And Methods: CDX2 protein expression was evaluated in 386 stage II and III primary colon cancers by immunohistochemical staining of tissue microarrays and by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis using formalin-fixed paraffin-embedded tissue sections of a matched subset of 23 recurrent and 23 non-recurrent colon cancers.

Expression of the immune modulator secretory leukocyte protease inhibitor (SLPI) in colorectal cancer liver metastases and matched primary tumors is associated with a poorer prognosis.

Secretory leukocyte protease inhibitor (SLPI), a pleiotropic protein expressed by healthy intestinal epithelial cells, functions as an inhibitor of NF-κB and neutrophil proteases and exerts antimicrobial activity. We previously showed SLPI suppresses intestinal epithelial chemokine production in response to microbial contact. Increased SLPI expression was recently detected in various types of carcinoma.

Prognostic value of microvessel density in stage II and III colon cancer patients: a retrospective cohort study.

Background: Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA.

Methods: Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients.

Molecular characterization of colorectal adenomas reveals POFUT1 as a candidate driver of tumor progression.

Removal of colorectal adenomas is an effective strategy to reduce colorectal cancer (CRC) mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. The present study aimed to characterize adenomas by in-depth molecular profiling, to obtain insights into altered biology associated with the colorectal adenoma-to-carcinoma progression.

CD31-positive microvessel density within adenomas of Lynch Syndrome patients is similar compared to adenomas of non-Lynch patients.

 Microsatellite instability accelerates colorectal cancer development in patients with Lynch syndrome (LS). Previous research showed that virtual chromoendoscopy increases detection of adenomas during colonoscopy surveillance of patients with LS. Because previous research revealed that Lynch patients have an increased vascular network in the oral mucosa, we hypothesized that increased vascularization of LS-associated adenomas is the cause of better detection with virtual chromoendoscopy.

MACROD2 expression predicts response to 5-FU-based chemotherapy in stage III colon cancer.

Background: Colorectal cancer (CRC) is caused by genetic aberrations. is commonly involved in somatic focal DNA copy number losses, in more than one-third of CRCs. In this study, we aimed to investigate the association of MACROD2 protein expression with clinical outcome in stage II and stage III colon cancer.

Consensus molecular subtype classification of colorectal adenomas.

Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI).

Identification of Differentially Expressed Splice Variants by the Proteogenomic Pipeline Splicify.

Proteogenomics, comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers.

Lumican and versican protein expression are associated with colorectal adenoma-to-carcinoma progression.

Background: One prominent event associated with colorectal adenoma-to-carcinoma progression is genomic instability. Approximately 85% of colorectal cancer cases exhibit chromosomal instability characterized by accumulation of chromosome copy number aberrations (CNAs). Adenomas with gain of chromosome 8q, 13q, and/or 20q are at high risk of progression to cancer.

Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases.

A prognostic classifier for patients with colorectal cancer liver metastasis, based on AURKA, PTGS2 and MMP9.

Background: Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value.

Methods: Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers.

Molecular imaging of aurora kinase A (AURKA) expression: Synthesis and preclinical evaluation of radiolabeled alisertib (MLN8237).

Introduction: Survival of patients after resection of colorectal cancer liver metastasis (CRCLM) is 36%-58%. Positron emission tomography (PET) tracers, imaging the expression of prognostic biomarkers, may contribute to assign appropriate management to individual patients. Aurora kinase A (AURKA) expression is associated with survival of patients after CRCLM resection.

MGL ligand expression is correlated to BRAF mutation and associated with poor survival of stage III colon cancer patients.

Colorectal cancer (CRC) is the third most prevalent cancer type worldwide with a mortality rate of approximately 50%. Elevated cell-surface expression of truncated carbohydrate structures such as Tn antigen (GalNAcα-Ser/Thr) is frequently observed during tumor progression. We have previously demonstrated that the C-type lectin macrophage galactose-type lectin (MGL), expressed by human antigen presenting cells, can distinguish healthy tissue from CRC through its specific recognition of Tn antigen.

Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis.

Objective: To investigate the individual and combined prognostic value of HIF1α, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM).

Background: In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC).

Expression of apoptosis regulating proteins identifies stage II and III colon cancer patients with high risk of recurrence.

Background And Objectives: Deregulation of apoptosis related genes may be associated with poor outcome in cancer. Aim of the present study was to investigate the prognostic role of expression levels of apoptosis related proteins in stage II and III colon cancer.

Methods: From tumor samples of 386 stage II and III colon cancer patients, DNA was isolated and tissue microarrays were constructed.

CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression.

Background: Gain of chromosome 20q is an important factor in the progression from colorectal adenomas to carcinomas. Genes that drive 20q gain are expected to show correlation of mRNA and protein expression levels with 20q DNA copy number status while functionally influencing cancer processes. CSE1L, DIDO1 and RBM39 are located on the 20q amplicon and affect processes such as cell viability and anchorage-independent growth in colorectal cancer.

Lumican and versican are associated with good outcome in stage II and III colon cancer.

Background: Tumor stroma plays an important role in the progression and metastasis of colon cancer. The glycoproteins versican and lumican are overexpressed in colon carcinomas and are associated with the formation of tumor stroma. The aim of the present study was to investigate the potential prognostic value of versican and lumican expression in the epithelial and stromal compartment of Union for International Cancer Control (UICC) stage II and III colon cancer.

Proximal fluid proteome profiling of mouse colon tumors reveals biomarkers for early diagnosis of human colorectal cancer.

Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC.

Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins.

Cell cycle proteins predict recurrence in stage II and III colon cancer.

Purpose: To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers.

Methods: From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, β-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA).

TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression.

Background And Objective: Progression of a colorectal adenoma to invasive cancer occurs in a minority of adenomas and is the most crucial step in colorectal cancer pathogenesis. In the majority of cases, this is associated with gain of a substantial part of chromosome 20q, indicating that multiple genes on the 20q amplicon may drive carcinogenesis. The aim of this study was to identify genes located on the 20q amplicon that promote progression of colorectal adenoma to carcinoma.

BCL2L1 has a functional role in colorectal cancer and its protein expression is associated with chromosome 20q gain.

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. The majority of CRCs, which develop from adenoma precursor lesions, show gain of chromosome arm 20q, where BCL2L1 is located. BCL2L1 is an important apoptosis regulating gene that codes for both an anti-apoptotic (Bcl-x(L)) and a pro-apoptotic (Bcl-x(S)) splice variant.