Prognostic Significance of MET Amplification and Expression in Gastric Cancer: A Systematic Review with Meta-Analysis

Peng, Zhi; Zhu, Yan; Wang, Qianqian; Gao, Jing; Li, Yilin; Li, Yanyan; Ge, Shaohua; Shen, Lin

doi:10.1371/journal.pone.0084502

Cited by 85 publications

(89 citation statements)

References 39 publications

(59 reference statements)

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“…Currently, there is no globally recognized standard testing platform for MET. Interpretation of IHC results across studies is hindered by lack of uniform scoring criteria for the different IHC testing methods or MET FISH (14). Recent studies have evaluated MET expression by the Ventana assay (12,14,16,(26)(27)(28)(29), with METpositive expression defined as IHC 3þ or 2þ staining in variable percentages of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Interpretation of IHC results across studies is hindered by lack of uniform scoring criteria for the different IHC testing methods or MET FISH (14). Recent studies have evaluated MET expression by the Ventana assay (12,14,16,(26)(27)(28)(29), with METpositive expression defined as IHC 3þ or 2þ staining in variable percentages of tumor cells. Our study showed a MET-positive expression prevalence rate of 39% by IHC in biopsy samples from Chinese advanced gastric or gastroesophageal junction patients when MET-positive expression was defined as !25% tumor cells with membrane protein staining at any intensity using the MET4 antibody.…”

Section: Discussionmentioning

confidence: 99%

“…For example, overexpression of HER2 has been shown to be predictive of outcomes in patients with advanced gastric cancer treated with trastuzumab (2). Furthermore, MET gene amplification and increased MET protein expression have been associated with advanced disease and poor prognosis in metastatic gastric cancer (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

“…Although others have explored the relationship between MET expression or MET amplification and prognosis in gastric cancer, most of these studies evaluated early-stage patients or mixedstage populations (13)(14)(15)(16)(17)(18)(19)(20), so the prognostic effect of MET in latestage disease remains unclear. Cancer stage may be an important factor when studying the prognostic effect of MET, as MET is associated with tumor invasion (11).…”

Section: Introductionmentioning

confidence: 99%

“…Cancer stage may be an important factor when studying the prognostic effect of MET, as MET is associated with tumor invasion (11). Moreover, prior studies primarily evaluated samples from resected tissue (13)(14)(15)(16)(17)(18)(19)(20). Biopsy samples are more relevant in advanced disease, and limited data about MET status in biopsy samples were available in these studies.…”

Section: Introductionmentioning

confidence: 99%

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Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or MET gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and MET amplification by FISH. MET-positive expression was defined as membrane protein staining in !25% of tumor cells. MET amplification was defined as MET:centromere 7 ratio >2.0. We tested the association of MET status with clinical characteristics and OS, and also evaluated the association between expression and amplification. One hundred sixty-eight patients were eligible. Of the evaluable samples, 53 of 137 (39%) were MET positive, eight of 134 (6%) were p-MET positive, and eight of 113 (7%) were MET amplified. Neither MET expression nor MET amplification were associated with clinical characteristics, except Lauren classification (P ¼ 0.04); MET amplification was associated with diffuse type. No significant OS difference was observed between MET-positive and MET-negative populations, regardless of first-line chemotherapy received. In 95 evaluable patients, MET expression was significantly associated with MET amplification (P < 0.001); all MET-amplified tumor samples showed some MET expression. In 96 evaluable patients, p-MET positivity was significantly associated with MET amplification (P < 0.001). Further evaluation in larger and independent sample sets is warranted to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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Effects of trastuzumab and afatinib on kinase activity in gastric cancer cell lines

et al. 2018

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The molecular mechanism of action of the HER2‐targeted antibody trastuzumab is only partially understood, and the direct effects of trastuzumab on the gastric cancer signaling network are unknown. In this study, we compared the molecular effect of trastuzumab and the HER kinase inhibitor afatinib on the receptor tyrosine kinase (RTK) network and the downstream‐acting intracellular kinases in gastric cancer cell lines. The molecular effects of trastuzumab and afatinib on the phosphorylation of 49 RTKs and 43 intracellular kinase phosphorylation sites were investigated in three gastric cancer cell lines (NCI‐N87, MKN1, and MKN7) using proteome profiling. To evaluate these effects, data were analyzed using mixed models and clustering. Moreover, proliferation assays were performed. Our comprehensive quantitative analysis of kinase activity in gastric cancer cell lines indicates that trastuzumab and afatinib selectively influenced the HER family RTKs. The effects of trastuzumab differed between cell lines, depending on the presence of activated HER2. The effects of trastuzumab monotherapy were not transduced to the intracellular kinase network. Afatinib alone or in combination with trastuzumab influenced HER kinases in all cell lines; that is, the effects of monotherapy and combination therapy were transduced to the intracellular kinase network. These results were confirmed by proliferation analysis. Additionally, the MET‐amplified cell line Hs746T was identified as afatinib nonresponder. The dependence of the effect of trastuzumab on the presence of activated HER2 might explain the clinical nonresponse of some patients who are routinely tested for HER2 expression and gene amplification in the clinic but not for HER2 activation. The consistent effects of afatinib on HER RTKs and downstream kinase activation suggest that afatinib might be an effective candidate in the future treatment of patients with gastric cancer irrespective of the presence of activated HER2. However, MET amplification should be taken into account as potential resistance factor.

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A genome‐wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns

Koike,

Osakabe,

Sugimoto

et al. 2024

The Journal of Pathology CR

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We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array‐based methods in 97 intestinal‐type IMNs, including 39 low‐grade dysplasias (LGDs), 37 high‐grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.

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Prognostic Significance of MET Amplification and Expression in Gastric Cancer: A Systematic Review with Meta-Analysis

Cited by 85 publications

References 39 publications

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Effects of trastuzumab and afatinib on kinase activity in gastric cancer cell lines

A genome‐wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns

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