Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

Lopez, Gianluca; Boggio, Francesca; Ferrero, Stefano; Fusco, Nicola; Gobbo, Alessandro Del

doi:10.3390/ijms19103014

Cited by 10 publications

(14 citation statements)

References 107 publications

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“…More data are available from expression-profiling analyses of clinical samples and/or animal models with CRC liver metastasis. In these studies, various gene signatures for colon-to-liver metastasis were suggested [ 131 , 132 ]. Although many identified signatures or molecular markers have been validated by other groups, yet none of them has been used as a diagnostic or prognostic tool applicable to clinical practice as reviewed [ 133 , 134 ].…”

Section: Experience In Predicting Markersmentioning

confidence: 99%

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Filip

Vymetalková

Petera

et al. 2020

IJMS

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Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.

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Section: Experience In Predicting Markersmentioning

confidence: 99%

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Filip

Vymetalková

Petera

et al. 2020

IJMS

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“…Colorectal adenoma-carcinoma sequence observed in most of the CRC cases in humans (CIN tumors, 84%) is associated with high frequency of DNA somatic copy number alterations (SCNA), with common mutations in APC , TP53 , KRAS , SMAD4 , and PIK3CA [7,10,18,19,20]. On the other hand, serrated neoplastic pathways associated with BRAF mutations, hMLH1 promoter hypermethylation, as well as MSI constitute 14–30% of CRC cases [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…A modulating influence of genetic variants of IGF2 receptor ( IGF2R) ( IGF2R c.5002 G > A and IGF2R c.901 C > G variants) on higher circulating IGF2 levels was also proven [59]. Based on TCGA data, it was proven that, among mutated genes typical for CRC (e.g., APC, TP53, SMAD4, PIK3CA , and KRAS ) [5,19,20], there were also copy-number changes including amplifications of ERBB2 and IGF2 [6,29]. Recent data also describes the CRIS-D subtype, which includes Wingless/Integrated (WNT) pathway activation as well as IGF2 overexpression and amplification.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer—From Basic Research to Potential Clinical Applications

Kasprzak

Adamek

2019

IJMS

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Colorectal cancer (CRC) is one of the most common cancers in men and women worldwide as well as is the leading cause of death in the western world. Almost a third of the patients has or will develop liver metastases. While genetic as well as epigenetic mechanisms are important in CRC pathogenesis, the basis of the most cases of cancer is unknown. High spatial and inter-patient variability of the molecular alterations qualifies this cancer in the group of highly heterogeneous tumors, which makes it harder to elucidate the mechanisms underlying CRC progression. Determination of highly sensitive and specific early diagnosis markers and understanding the cellular and molecular mechanism(s) of cancer progression are still a challenge of the current era in oncology of solid tumors. One of the accepted risk factors for CRC development is overexpression of insulin-like growth factor 2 (IGF2), a 7.5-kDa peptide produced by liver and many other tissues. IGF2 is the first gene discovered to be parentally imprinted. Loss of imprinting (LOI) or aberrant imprinting of IGF2 could lead to IGF2 overexpression, increased cell proliferation, and CRC development. IGF2 as a mitogen is associated with increased risk of developing colorectal neoplasia. Higher serum IGF2 concentration as well as its tissue overexpression in CRC compared to control are associated with metastasis. IGF2 protein was one of the three candidates for a selective marker of CRC progression and staging. Recent research indicates dysregulation of different micro- and long non-coding RNAs (miRNAs and lncRNAs, respectively) embedded within the IGF2 gene in CRC carcinogenesis, with some of them indicated as potential diagnostic and prognostic CRC biomarkers. This review systematises the knowledge on the role of genetic and epigenetic instabilities of IGF2 gene, free (active form of IGF2) and IGF-binding protein (IGFBP) bound (inactive form), paracrine/autocrine secretion of IGF2, as well as mechanisms of inducing dysplasia in vitro and tumorigenicity in vivo. We have tried to answer which molecular changes of the IGF2 gene and its regulatory mechanisms have the most significance in initiation, progression (including liver metastasis), prognosis, and potential anti-IGF2 therapy in CRC patients.

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“…Molecular alterations can be used for diagnostic [1], prognostic [2,3,4,5,6,7] and predictive [7] purposes. Furthermore, the use of bioinformatics and machine learning could help to define and validate novel “omics-based” markers with important diagnostic and prognostic implications [1].…”

mentioning

confidence: 99%

“…miRNAs are released into exosomes, a process thought to mediate liver metastasis through the preparation of the pre-metastatic niche [10]. Although several other biomarkers have been linked to liver metastasis, none have provided sufficiently robust results to confirm their involvement [7]. Long non-coding RNAs (lncRNAs) also play an important role in different biological processes involved in cancer.…”

mentioning

confidence: 99%

Special Issue on Basic and Translational Research in Colorectal Cancer

Ulivi

Scarpi

Passardi

2019

IJMS

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Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

Cited by 10 publications

References 107 publications

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer—From Basic Research to Potential Clinical Applications

Special Issue on Basic and Translational Research in Colorectal Cancer

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