The tumour–stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients

Masuya, Daiki; Huang, Cheng-long; Liu, D; Nakashima, Takashi; Kameyama, Kotaro; Haba, Reiji; Ueno, Masaki; Yokomise, Hiroyasu

doi:10.1038/sj.bjc.6601718

Cited by 129 publications

(116 citation statements)

References 33 publications

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“…Here, we also show that high expression of pCMET is related to poor prognosis and high expression of E-cadherin is related to improved outcome (Bremnes et al, 2002;Masuya et al, 2004b). We found KRAS mutations to be related to favourable prognosis, which contrasts the existing literature that indicates these mutations to be a negative prognostic factor (Van Zandwijk et al, 1995;Miyake et al, 1999).…”

Section: Discussioncontrasting

confidence: 54%

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Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

et al. 2008

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The purpose of this study is to evaluate the prognostic value of the combined assessment of multiple molecular markers related to the epidermal growth factor receptor (EGFR) pathway in resected non-small cell lung cancer (NSCLC) patients. Tumour specimens of 178 NSCLC patients were collected and analysed for EGFR and KRAS mutation status by DNA sequencing, and for EGFR copy number by fluorescent in situ hybridisation. Tissue microarrays were generated and used to determine the expression of multiple EGFR pathway-related proteins by immunohistochemistry. We analysed the association between each marker and patient prognosis. Univariate analyses for each clinical variable and each molecular marker were performed using Kaplan -Meier curves and log-rank tests. From these results, we selected the variables KRAS mutations and expression of cytoplasmic EGFR, granular pERK, nuclear pSTAT3, cytoplasmic E-cadherin and cytoplasmic pCMET to enter into a Cox proportional hazards model, along with stage as the strongest clinical variable related with prognosis. Of the EGFR-related markers evaluated here, the markers EGFR, pERK, pSTAT3, E-cadherin, pCMET and mutations in KRAS were associated with survival when analysed in combination in our patient cohort, with P ¼ 0.00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary.

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Section: Discussioncontrasting

confidence: 54%

“…Several other markers have also been associated with poor prognosis in NSCLC (EGFR, CMET, E-cadherin, pAKT (Takanami et al, 1996;Bremnes et al, 2002;David et al, 2004;Deeb et al, 2004;Masuya et al, 2004a)), but at present there is no single marker that can be used to guide therapy or predict prognosis of NSCLC patients.…”

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confidence: 99%

Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

et al. 2008

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“…In striking contrast to our results, expression of MET/HGF in solid malignancies has been associated with unfavorable clinical outcomes, 16,17,19,20,22,25 although a few studies identified a favorable prognostic impact of MET. 36,37 Expression of MST1R is also associated with unfavorable clinical outcomes [38][39][40] or not associated with prognosis.…”

Section: Discussioncontrasting

confidence: 99%

“…24 Previous studies also report that MET/HGF has prognostic significance in many malignant tumors. 19,20,25 MST1R (RON), an RTK with homology to MET, is involved in tumor progression and metastasis. 26,27 MST1R is overexpressed in human epithelial malignancies.…”

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confidence: 99%

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

et al. 2013

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MST1R (RON) and MET are receptor tyrosine kinase gene family members that form a noncovalent complex on the cell surface, a critical step in tumor progression. A recent study suggested a prognostic role of MET expression in Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL). The purpose of this study was to examine the prognostic significance of MET and MST1R expression in cHL. The prognostic impact of MET and MST1R was examined in 100 patients with cHL (median age: 32 years) by immunohistochemistry and mRNA in situ hybridization. The median follow-up time was 95 months (interquartile range: 42-126 months). MET or MST1R protein expression was associated with high MET or MST1R mRNA expression, respectively. Thirty-eight patients (38%) expressed MET protein in HRS cell, which was associated with better overall survival (P ¼ 0.004). Twenty-six patients (26%) expressed MST1R protein, which was associated with better overall survival (P ¼ 0.022) and event-free survival (P ¼ 0.021). Multivariate analysis identified MET protein as an independent prognostic factor for overall survival and MST1R protein as an independent prognostic factor for event-free survival. Subgroup analysis according to Ann Arbor stage showed that expressions of MET and MST1R protein have prognostic impact in the advanced stage only. In particular, coexpression of MST1R and MET protein was associated with a better survival outcome than MET or MST1R expression alone or no expression. This study suggests that MET and MST1R are independent prognostic factors in classical cHL, and may allow the identification of a subgroup of cHL patients who require more intensive therapy.

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“…4 Modern literature accordingly emphasizes the search for new biological prognostic markers in order to refine the prognostic value contributed by tumor staging and histopathological analyses. [4][5][6][7][8][9] Among the biological markers whose diagnostic and prognostic values have already been demonstrated in various types of cancers are galectins in general, [10][11][12] and galectin-3 in particular. 13,14 In all, 14 galectins have been identified to date 10,11 which function as cell receptors for the N-acetyl-lactosamine (LacNAC) moieties present on most of the extracellular matrix components.…”

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confidence: 99%

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

et al. 2005

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The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers.In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity Â Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P ¼ 0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P ¼ 0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P ¼ 0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P ¼ 0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.

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The tumour–stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients

Cited by 129 publications

References 33 publications

Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

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