MET Gene Amplification and Overexpression in Chinese Non–Small-Cell Lung Cancer Patients Without EGFR Mutations

Song, Zhengbo; Wang, Xuzhou; Zheng, Yuhui; Su, Hai‐Yan; Zhang, Yiping

doi:10.1016/j.cllc.2016.09.011

Cited by 14 publications

(21 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2007, Lutterbach et al first reported MET gene amplification and overexpression in non-small-cell lung cancer cell lines 27 and their association with poor overall survival. 28 , 29 In our present study, we found the MET expression rate to be 36.8% by using immunohistochemistry, which was in agreement with previous reports. 29 , 30 We found a positive correlation between MET protein expression and primary tumor SUV max , which was significantly higher in patients with positive expression of MET than in those with negative expression of MET.…”

Section: Discussionsupporting

confidence: 93%

“… 28 , 29 In our present study, we found the MET expression rate to be 36.8% by using immunohistochemistry, which was in agreement with previous reports. 29 , 30 We found a positive correlation between MET protein expression and primary tumor SUV max , which was significantly higher in patients with positive expression of MET than in those with negative expression of MET. Tian et al also reported similar observation in human colorectal carcinoma.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

<sup>18</sup>F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

An¹,

Zhou²,

Liu³

et al. 2017

OTT

View full text Add to dashboard Cite

ObjectiveMET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and 18F-FDG uptake has not been investigated yet. This study aimed to determine the correlation of MET expression with 18F-FDG uptake on PET-CT scan and whether or not 18F-FDG PET/CT can be used to predict the MET status of lung adenocarcinoma patients.Patients and methodsFifty-seven lung adenocarcinoma patients were analyzed in our study. Maximum standardized uptake value (SUVmax) was calculated in all PET/CT images. The expression levels of MET and two important glycolysis-related markers, glucose transporter 1 (GLUT1) and pyruvate kinase M2, were analyzed by immunohistochemistry of tissues. Spearman rank correlation was used to analyze the association between MET expression and SUVmax. In vitro MET knockdown in lung adenocarcinoma cells was used to examine the role of MET in tumor metabolism. The effect of MET on GLUT1 expression was investigated using Western blot assay and quantitative polymerase chain reaction.ResultsSUVmax was positively correlated with the expression levels of MET (r=0.458; P<0.001) and GLUT1 (r=0.551; P<0.001). SUVmax was significantly higher in patients with positive MET expression than in those with negative MET expression (9.92±6.62 vs 4.60±3.00; P=0.002). MET knockdown in lung adenocarcinoma cells led to a significant decrease in GLUT1 expression and 18F-FDG uptake.ConclusionMET could increase 18F-FDG uptake by upregulating GLUT1 expression. 18F-FDG PET/CT could be used to predict the MET status of lung adenocarcinoma patients and to supply valuable information to guide targeted therapy.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

<sup>18</sup>F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

An¹,

Zhou²,

Liu³

et al. 2017

OTT

View full text Add to dashboard Cite

show abstract

“…Similar discordance also has been observed in gastric-intestinal cancer studies by tissue microarray (unpublished data). In addition, the clinical impact of MET overexpression has been controversial, with some studies showing negative impact [ 33 ] and others showing the opposite results [ 32 ]. Our data did not show independent impact by MET overexpression alone assessed by IHC.…”

Section: Discussionmentioning

confidence: 99%

MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer

et al. 2018

View full text Add to dashboard Cite

To investigate the prognostic impact of MET copy number (MET-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for MET-CN using fluorescence in situ hybridization (FISH). We correlated MET-CN status with patient overall survival (OS) and optimized MET-FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.7% of patients had distant metastases. There were 170 patients with stages I-III and 214 patients with stage IV disease. Based on the MET-CN and MET/CEP7 ratio the patients were classified into 3 categories: MET-amplification (METamp): MET/CEP7 ≥ 2 or MET-CN ≥ 5; MET-CN-gain (METcng): MET-CN ≥ 4 to < 5; and MET-negative (METneg): MET-CN < 4. METamp was associated with high fatality (P=.036) and stage IV tumors (P=.038). In patients with stages I-III NSCLC, patients in the METamp category had the shortest OS (P=.015) and more often developed distant metastases within 1 year (P=.004). In patients with stage IV tumors, METamp did not further impact the OS. Patients in the METcng category had the longest OS (P=.053). Multivariate analysis confirmed METamp to be an independent high-risk factor (HR 3.26; P=.026) and predicted earlier progression to distant metastasis (HR 4.86; P=.001). In conclusion, we suggest that the MET-FISH criteria presented optimizes risk stratification by defining 3 categories of NSCLC patients. METamp is an independent risk factor predicting early distant metastasis and patients with METcng could represent a lower-risk group.

show abstract

“…However, CSE/B[α]P‐induced c‐MET activation was not observed in HCC827 or PC9 cells and did not cause EGFR TKI resistance. Consistent to our findings, c‐MET amplification was frequently detected in wtEGFR, but not in mutant EGFR‐expressing NSCLC patients, and is associated with a poor prognosis (Song et al ., ). Since HCC827 cells express EGFR activating mutant, which dominantly controls pro‐survival Akt signal, cigarette smoke may only switch the oncogene addition from the EGFR to MET pathway in wtEGFR‐expressing NSCLC cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke enhances oncogene addiction to c‐MET and desensitizes EGFR‐expressing non‐small cell lung cancer to EGFR TKIs

Cheng

Chen

et al. 2018

Molecular Oncology

View full text Add to dashboard Cite

Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non‐small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of EGFR TKIs. In this study, our data showed that chronic exposure to cigarette smoke extract (CSE) or tobacco smoke‐derived carcinogen benzo[α]pyrene, B[α]P, but not nicotine‐derived nitrosamine ketone (NNK), reduced the sensitivity of wild‐type EGFR‐expressing NSCLC cells to EGFR TKIs. Treatment with TKIs almost abolished EGFR tyrosine kinase activity but did not show an inhibitory effect on downstream Akt and ERK pathways in B[α]P‐treated NSCLC cells. CSE and B[α]P transcriptionally upregulate c‐MET and activate its downstream Akt pathway, which is not inhibited by EGFR TKIs. Silencing of c‐MET reduces B[α]P‐induced Akt activation. The CSE‐treated NSCLC cells are sensitive to the c‐MET inhibitor crizotinib. These findings suggest that cigarette smoke augments oncogene addiction to c‐MET in NSCLC cells and that MET inhibitors may show clinical benefits for lung cancer patients with a smoking history.

show abstract

MET Gene Amplification and Overexpression in Chinese Non–Small-Cell Lung Cancer Patients Without EGFR Mutations

Cited by 14 publications

References 22 publications

<sup>18</sup>F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

<sup>18</sup>F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma

MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer

Cigarette smoke enhances oncogene addiction to c‐MET and desensitizes EGFR‐expressing non‐small cell lung cancer to EGFR TKIs

Contact Info

Product

Resources

About