Soluble c‐Met protein as a susceptible biomarker for gastric cancer risk: A nested case‐control study within the Korean Multicenter Cancer Cohort

Yang, Jae Jeong; Yang, Ji Hyun; Kim, Jungkon; Hyun, Sangwon; Cho, Lisa Y.; Ko, Kwang Pil; Shin, Aesun; Choi, Bo Youl; Kim, Hyun Ja; Han, Dong Soo; Eun, Chang Soo; Song, Kyu Sang; Kim, Yong‐Sung; Chang, Soo-Ho; Shin, Hai Rim; Kang, Daehee; Yoo, Keun Young; Park, Sung Sup

doi:10.1002/ijc.27861

Cited by 16 publications

(16 citation statements)

References 18 publications

(44 reference statements)

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“…These phenomena were similar to those shown in a breast cancer study in which MET shedding correlated with malignancy in cultured cells and tumor burden in tumor xenograft mouse models (48). Conversely, Yang et al demonstrated the beneficial effects of high sMET concentrations in human plasma, showing that the overall median plasma concentration of sMET in patients with gastric cancer was lower than in controls, and sMET levels decreased as the onset of cancer drew nearer (49). This study also investigated the interactions between CagA-related genes and sMET protein concentration in the development of gastric cancer, suggesting that the genetic background of different cancer types may influence the application of MET concentration in the diagnosis/prognosis of human cancers.…”

Section: Discussionsupporting

confidence: 79%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers. Molecular & Cellular Proteomics

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Section: Discussionsupporting

confidence: 79%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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“…In contrast to the above studies, in a case-control set of 290 subjects, the sMET level was significantly decreased among gastric cancer patients compared to controls (p < .0001) [176]. Intriguingly, this longitudinal cohort study showed that soluble MET levels appeared to decrease before the onset of gastric cancer [176].…”

Section: Iv-circulating Met Levels As Diagnostic and Prognostic Biomacontrasting

confidence: 78%

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Moosavi

Giovannetti

Saso³

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

123

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Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.

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“…(a) Positions of missense and deletion mutations in each domain of MET . The deletion mutations in extracellular immunoglobulin‐like fold–plexin–transcription factor ( IPT ) domains and the intracellular juxtamembrane ( JM ) domain are caused by exon skipping . (b) Crystal structures of MET tyrosine kinase ( TK ) domain and positions of missense activating mutations found in patients with papillary renal cell carcinoma.…”

Section: Met Mutationsmentioning

confidence: 99%

Hepatocyte growth factor/MET in cancer progression and biomarker discovery

et al. 2017

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Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3‐D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases for invasion–metastasis and resistance, respectively, against targeted drugs in cancers. Recent studies indicated that MET in tumor‐derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification‐induced MET activation and ligand‐dependent MET activation in an autocrine/paracrine manner are causes for resistance to epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors. Hepatocyte growth factor secreted in the tumor microenvironment contributes to the innate and acquired resistance to RAF inhibitors. Changes in serum/plasma HGF, soluble MET (sMET), and phospho‐MET have been confirmed to be associated with disease progression, metastasis, therapy response, and survival. Higher serum/plasma HGF levels are associated with therapy resistance and/or metastasis, while lower HGF levels are associated with progression‐free survival and overall survival after treatment with targeted drugs in lung cancer, gastric cancer, colon cancer, and malignant melanoma. Urinary sMET levels in patients with bladder cancer are higher than those in patients without bladder cancer and associated with disease progression. Some of the multi‐kinase inhibitors that target MET have received regulatory approval, whereas none of the selective HGF‐MET inhibitors have shown efficacy in phase III clinical trials. Validation of the HGF‐MET pathway as a critical driver in cancer development/progression and utilization of appropriate biomarkers are key to development and approval of HGF‐MET inhibitors for clinical use.

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Soluble c‐Met protein as a susceptible biomarker for gastric cancer risk: A nested case‐control study within the Korean Multicenter Cancer Cohort

Cited by 16 publications

References 18 publications

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Hepatocyte growth factor/MET in cancer progression and biomarker discovery

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