Metastatic Spread Emerging From Liver Metastases of Colorectal Cancer

Rahbari, Nuh N.; Bork, Ulrich; Schölch, Sebastian; Reißfelder, Christoph; Thorlund, Kristian; Betzler, Alexander; Kahlert, Christoph; Schneider, Martin; Ulrich, Alexis; Büchler, Markus W.; Weitz, Jürgen; Koch, Moritz

doi:10.1097/sla.0000000000001341

Cited by 30 publications

(30 citation statements)

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“…CRC is among the most commonly investigated tumor entities [2, 17, 33, 34]. The most prominent signaling pathway in CRC is Wnt signaling, its activation (most frequently by inactivating APC mutations) usually initiates the adenoma-carcinoma sequence and thus colorectal tumorigenesis [35].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical data and samples are being collected continuously at the Department of Surgery of University Hospital Heidelberg; our management of patients with colorectal cancer has been published in detail before [16, 17]. Tumor and mucosa samples were collected from 59 CRC patients (of all UICC stages), which underwent tumor resection at the Department of General, Visceral and Transplantation Surgery at the University Hospital in Heidelberg between October 2006 and July 2012.…”

Section: Methodsmentioning

confidence: 99%

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LDB1overexpression is a negative prognostic factor in colorectal cancer

et al. 2016

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BackgroundColorectal cancer (CRC) is the third most common cancer in western countries and is driven by the Wnt signaling pathway. LIM-domain-binding protein 1 (LDB1) interacts with the Wnt signaling pathway and has been connected to malignant diseases. We therefore aimed to evaluate the role of LDB1 in CRC.ResultsOverexpression of LDB1 in CRC is associated with strikingly reduced overall and metastasis free survival in all three independent patient cohorts. The expression of LDB1 positively correlates with genes involved in the Wnt signaling pathway (CTNNB1, AXIN2, MYC and CCND1). Overexpression of LDB1 in CRC cell lines induced Wnt pathway upregulation as well as increased invasivity and proliferation. Upon separate analysis, the role of LDB1 proved to be more prominent in proximal CRC, whereas distal CRC seems to be less influenced by LDB1.Materials and MethodsThe expression of LDB1 was measured via RT-qPCR in 59 clinical tumor and normal mucosa samples and correlated to clinical end-points. The role of LDB1 was examined in two additional large patient cohorts from publicly available microarray and RNAseq datasets. Functional characterization was done by lentiviral overexpression of LDB1 in CRC cell lines and TOP/FOP, proliferation and scratch assays.ConclusionsLDB1 has a strong role in CRC progression, confirmed in three large, independent patient cohorts. The in vitro data confirm an influence of LDB1 on the Wnt signaling pathway and tumor cell proliferation. LDB1 seems to have a more prominent role in proximal CRC, which confirms the different biology of proximal and distal CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

LDB1overexpression is a negative prognostic factor in colorectal cancer

et al. 2016

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“…Also, metastases appear to shed new cells of an invasive type, thus giving further rise to the metastatic tumor phenotype[37]. Remaining challenges is the isolation and characterization of CTCs and the sensitivity and specificity in detection of ctDNA[38].…”

Section: Liquid Biopsies: Circulating Tumor Cells and Circulating Tummentioning

confidence: 99%

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

Veen

Søreide

2017

WJGO

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In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from “what is taken out” (e.g., how much liver has to be resected) to “what is left behind” (that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.

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“…Other studies have been done where intraoperative blood samples were taken such as portal venous blood or liver venous blood. These samples can be run as normal CellSearch CTC samples [132,133].…”

Section: Use Of Cellsearch For Other Body Fluidsmentioning

confidence: 99%

Improving the CellSearch® system

Swennenhuis

Dalum

Zeune

et al. 2016

Expert Review of Molecular Diagnostics

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Introduction:The CellSearch ® CTC test enumerates tumor cells present in 7.5 ml blood of cancer patients. improvements, extensions and different utilities of the cellsearch system are discussed in this paper. Areas covered: This paper describes work performed with the CellSearch system, which go beyond the normal scope of the test. All results from searches with the search term 'CellSearch' from Web of Science and PubMed were categorized and discussed. Expert commentary: The CellSearch Circulating Tumor Cell test captures and identifies tumor cells in blood that are associated with poor clinical outcome. How to best use CTC in clinical practice is being explored in many clinical trials. The ability to extract information from the CTC to guide therapy will expand the potential clinical utility of CTC. ARTICLE HISTORY

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Metastatic Spread Emerging From Liver Metastases of Colorectal Cancer

Abstract: Colorectal liver metastases shed intact tumor cells with an invasive phenotype. Metastasis size serves as a surrogate marker for metastatic activity of colorectal liver metastases.

Cited by 30 publications

References 53 publications

LDB1overexpression is a negative prognostic factor in colorectal cancer

LDB1overexpression is a negative prognostic factor in colorectal cancer

Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

Improving the CellSearch® system

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