Clinical impact of c‐<scp>MET</scp> expression and genetic mutational status in colorectal cancer patients after liver resection

Shoji, Hirokazu; Yamada, Yasuhide; Taniguchi, Hirokazu; Nagashima, Kengo; Okita, Natsuko; Takashima, Atsuo; Honma, Yoshitaka; Iwasa, Satoru; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro

doi:10.1111/cas.12453

Cited by 24 publications

(21 citation statements)

References 28 publications

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“…Therefore, it would be reasonable to expect that the frequency of cases with MET overexpression would be higher in the later (73% versus 22%). Similar effect occurred in CRC comparing Voutsina et al 54 , Ma et al 49 and Shoji et al 56 studies. In NSCLC, MET overexpression was reported by Spigel et al 61 in 52% and by Masuya et al 32 in 41% of the patients.…”

Section: Molecular Mechanisms Of Met Activation In Carcinogenesissupporting

confidence: 69%

“…IHC was the common technique used to determine MET expression. Overexpression of the MET protein has been more commonly investigated in various solid tumors as seen in Table 2 , with studies in bladder 45 , breast 37 - 39 , 46 - 51 , colorectal 49 , 52 - 56 , gastric 57 , hepatobiliary 58 , head and neck 42 , 43 , lung 32 , 49 , 59 - 61 , ovarian 49 and renal 49 , 62 cancers.…”

Section: Molecular Mechanisms Of Met Activation In Carcinogenesismentioning

confidence: 99%

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Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

2016

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The MET signaling pathway plays an important role in normal physiology and its deregulation has proved critical for development of numerous solid tumors. Different technologies have been used to investigate the genomic and proteomic status of MET in cancer patients and its association with disease prognosis. Moreover, with the development of targeted therapeutic drugs, there is an urgent need to identify potential biomarkers for selection of patients who are more likely to derive benefit from these agents. Unfortunately, the variety of technical platforms and analysis criteria for diagnosis has brought confusion to the field and a lack of agreement in the evaluation of MET status as a prognostic or predictive marker for targeted therapy agents. We review the molecular mechanisms involved in the deregulation of the MET signaling pathway in solid tumors, the different technologies used for diagnosis, and the main factors that affect the outcome, emphasizing the urge for completing analytical and clinical validation of these tests. We also review the current clinical studies with MET targeted agents, which mostly focus on lung cancer.

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Section: Molecular Mechanisms Of Met Activation In Carcinogenesissupporting

confidence: 69%

Section: Molecular Mechanisms Of Met Activation In Carcinogenesismentioning

confidence: 99%

Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

2016

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“…Seven of the 14 studies included in the systematic literature review reported RFS. Multivariable Cox regression analysis was performed for all seven studies, and the HR data were pooled in a separate meta‐analysis ( Fig .…”

Section: Resultsmentioning

confidence: 99%

“…3). The seven studies reported a total of 906 patients undergoing resection of CLM; in these patients the KRAS Petrowsky et al 19 Nash et al 16 Stremitzer et al 13 Huang et al 20 Umeda et al 23 Vauthey et al 14 Karagkounis et al 12 Kemeny et al 24 Overall (I 2 = 0·0%, P = 0·965) Cejas et al 18 Isella et al 21 Stremitzer et al 13 Shoji et al 25 Vauthey et al 14 Karagkounis et al 12 Kemeny et al 24 Overall (I 2 = 0·0%, P = 0·997)…”

Section: Kras Mutation and Recurrence-free Survivalmentioning

confidence: 99%

Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases

Brudvik

Kopetz

et al. 2015

British Journal of Surgery

177

126

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Background: In patients with advanced colorectal cancer, KRAS mutation status predicts response to treatment with monoclonal antibody targeting the epithelial growth factor receptor (EGFR). Recent reports have provided evidence that KRAS mutation status has prognostic value in patients with resectable colorectal liver metastases (CLM) irrespective of treatment with chemotherapy or anti-EGFR therapy. A meta-analysis was undertaken to clarify the impact of KRAS mutation on outcomes in patients with resectable CLM.Methods: PubMed, Embase and Cochrane Library databases were searched systematically to identify full-text articles reporting KRAS-stratified overall (OS) or recurrence-free (RFS) survival after resection of CLM. Hazard ratios (HRs) and 95 per cent c.i. from multivariable analyses were pooled in meta-analyses, and a random-effects model was used to calculate weight and overall results. Results:The search returned 355 articles, of which 14, including 1809 patients, met the inclusion criteria. Eight studies reported OS after resection of CLM in 1181 patients. The mutation rate was 27⋅6 per cent, and KRAS mutation was negatively associated with OS (HR 2⋅24, 95 per cent c.i. 1⋅76 to 2⋅85). Seven studies reported RFS after resection of CLM in 906 patients. The mutation rate was 28⋅0 per cent, and KRAS mutation was negatively associated with RFS (HR 1⋅89, 1⋅54 to 2⋅32).Conclusion: KRAS mutation status is a prognostic factor in patients undergoing resection of colorectal liver metastases and should be considered in the evaluation of patients having liver resection.

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“…(9)(10)(11) Previous reports showed that HGF could induce EMT in PDAC cells; moreover, the HGF receptor, c-Met, was identified as a dominant pancreatic CSC marker. (14) Therefore, it was expected that c-Met expression of PDAC can be a prognostic marker despite no report assuming that, and actually, c-Met expression was previously identified as an indicator of poor prognosis in various cancers, (32,33) and a c-Met inhibitor was developed as a candidate drug for treating advanced hepatocellular carcinoma. (34) Our results firstly elucidated the role of c-Met expression in PDAC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐181b‐5p, ETS1, and the c‐Met pathway exacerbate the prognosis of pancreatic ductal adenocarcinoma after radiation therapy

et al. 2017

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Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens show remnant tumor cells, which indicate that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the EMT and the presence of CSCs, were reported to be associated with resistance in various cancers. Previous reports showed that HGF could induce EMT in PDAC cells; moreover, the HGF receptor, c‐Met, was identified as a dominant pancreatic CSC marker. However, the clinical significance of c‐Met expression remains unclear. So, we hypothesized that remnant PDAC tissue after CRT might harbor cells with high c‐Met expression, and these cells may exacerbate patients’ prognosis. In the immunohistochemical analysis, we showed that preoperative CRT was significantly associated with high c‐Met expression; moreover, high c‐Met expression was a significant marker of a dismal prognosis. Next, we investigated mechanisms of c‐Met upregulation in PDAC cells. We established GEM‐resistant and radioresistant PDAC cells to analyze the transcriptome involved in c‐Met expression. The microarray data for the established radiation‐resistant PDAC cells indicated miR‐181b‐5p downregulation, which targets ETS1, one of the transcription factors for c‐Met, and it was shown that radiation exposure induced c‐Met expression through ETS1 increase by the suppression of miR‐181b‐5p. These results suggested that targeting these mechanisms may promote the development of a novel multidisciplinary treatment strategy for improving preoperative CRT efficiency.

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Clinical impact of c‐MET expression and genetic mutational status in colorectal cancer patients after liver resection

Cited by 24 publications

References 28 publications

Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?

Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases

MicroRNA‐181b‐5p, ETS1, and the c‐Met pathway exacerbate the prognosis of pancreatic ductal adenocarcinoma after radiation therapy

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