Prognostic value of MET copy number gain in non-small-cell lung cancer: an updated meta-analysis

Kim, Jung Han; Kim, Hyeong Su; Kim, Bum Joon

doi:10.7150/jca.24980

Cited by 24 publications

(18 citation statements)

References 63 publications

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Section: Ii-b-met Gene Amplificationmentioning

confidence: 99%

“…There are a few meta-analyses in the literature on the prognostic role of MET CNG in NSCLC [64,67,118]. A recent meta-analysis combined the results from 21 studies that involved 7647 patients and showed the association between MET CNG and inferior OS (HR 1.45, 95% CI 1.16-1.80) [64]. Subgroup analyses based on histology and ethnicity indicated that MET CNG significantly correlated with shorter survival, especially in patients with adenocarcinoma (HR 1.41, 95% CI 1.11-1.79) and in Asian populations (HR 1.58, 95% CI 1.32-1.88).…”

Section: Ii-b-met Gene Amplificationmentioning

confidence: 99%

“…For example, high MET expression detected by IHC in gastric cancer ranged from 20-80% [73]. Similarly, MET amplification detected by FISH in NSCLC varied from 1-40% [64].…”

Section: Iii-met Aberrant Activation In Tumor Tissue As a Predictive mentioning

confidence: 99%

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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

125

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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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Section: Ii-b-met Gene Amplificationmentioning

confidence: 99%

Section: Ii-b-met Gene Amplificationmentioning

confidence: 99%

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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

125

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“…Alterations on transcription level of MET gene, which includes MET amplification and MET exon 14 skipping mutation could be the potential mechanisms (21). Additionally, high gene copy number (GCN) of MET was also found be an adverse survival indicator in several studies (59)(60)(61). Nevertheless, MET positivity was notably higher, with a prevalence ranged up-till 70% among NSCLC, compared with MET mutations (around 4%) (58).…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Role of MET Protein Expression Among Surgically Resected Non-small Cell Lung Cancer Patients: A Meta-Analysis

Deng

Chen

et al. 2019

Front. Oncol.

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Objectives: MET protein expression has been reported to be in relevance with the survival of NSCLC patients in various studies, yet the results were inconsistent. The purpose of our study set out to determine the prognostic role of both c-MET and p-MET expression among NSCLC that underwent surgical resection. Methods: Data were obtained from retrospective cohort studies by searching on PubMed, Cochrane Library, EMBASE and Web of Science, and a meta-analysis was performed to assess the prognostic role of MET expression among NSCLC. Results: Totally 18 literatures including 5,572 surgically resected NSCLC cases staged I-IV were included for data synthesis. The positive rate of c-MET and p-MET was 1,753/4,315 and 135/1,257. The pooled hazard ratios (HRs) regarding c-MET and p-MET expression for overall survival (OS) was 1.623 (95% CI: 1.176-2.240, p = 0.003) and 1.710 (95% CI: 0.823-3.533, p = 0.15), respectively. Subgroup analysis results on Asian (HR = 2.115, p < 0.001), adenocarcinoma (HR = 2.220, p < 0.001) and rabbit polyclonal antibodies (HR = 2.107, p < 0.001) etc. were also indicative. Conclusion: C-MET over-expression among NSCLC patients that underwent surgical resection is a prognostic factor that indicated adverse survival on OS. Whereas, p-met didn't appear to have an impact on the prognosis of NSCLC. The studies are need and the topic could be re-valued by then.

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“…The frequencies of METex14 mutations was 1.7-4.3% in metastatic lung adenocarcinomas, according to NGS analyses. [46][47][48]55,58 METex14-skipping mutations tend to be more frequent in relatively elderly populations and mutually exclusive of other lung cancer-driver mutations. 71,72 METex14-skipping mutations have been identified across different major histological subtypes of lung cancers, eg adenosquamous (8.2%) or sarcomatoid subtypes (7.7%), adenocarcinomas (2.9%) and squamous-cell carcinomas (2.1%).…”

Section: Mutationsmentioning

confidence: 99%

<p>Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date</p>

Bylicki¹,

Paleiron²,

Assié³

et al. 2020

OTT

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The c-MET proto-oncogene (MET) plays an important role in lung oncogenesis, affecting cancer-cell survival, growth and invasiveness. The MET receptor in non-small-cell lung cancer (NSCLC) is a potential therapeutic target. The development of high-output nextgeneration sequencing techniques has enabled better identification of anomalies in the MET pathway, like the MET exon-14 (METex14) mutation. Moreover, analyses of epidermal growth factor-receptor (EGFR) and mechanisms of resistance to tyrosine-kinase inhibitors (TKIs) demonstrated the importance of MET amplification as an escape mechanism in patients with TKI-treated EGFR-mutated NSCLCs. This review summarizes the laboratory findings on MET and its anomalies, trial results on METex14 alterations and MET amplification in non-EGFR mutated NSCLCs, and acquired resistance to TKI in EGFR-mutated NSCLCs. The outcomes of the first trials with anti-MET agents on non-selected NSCLC patients or those selected for MET overexpression were disappointing. Two situations seem the most promising today for the use of anti-MET agents to treat these patients: tumors harboring METex14 and those EGFR-sensitive mutation mutated under TKI-EGFR with a MET-amplification mechanism of resistance or EGFR-resistance mutation.

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Prognostic value of MET copy number gain in non-small-cell lung cancer: an updated meta-analysis

Cited by 24 publications

References 63 publications

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

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

The Prognostic Role of MET Protein Expression Among Surgically Resected Non-small Cell Lung Cancer Patients: A Meta-Analysis

<p>Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date</p>

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