c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head-and-Neck Squamous Cell Carcinoma Treated With Chemoradiation

Baschnagel, Andrew M.; Williams, Letitia; Hanna, Alaa; Chen, P.Y.; Krauss, Daniel; Pruetz, Barbara L.; Åkervall, Jan; Wilson, George

doi:10.1016/j.ijrobp.2013.11.030

Cited by 12 publications

(20 citation statements)

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“…After title and abstract checking, 36 studies remained for the further evaluating in details, in which 15 articles were excluded for there were no enough data to calculate the survival rate [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], one article was removed because of duplication [28]. So, a total of 20 publications were fulfilled the eligibility criteria [5][6][7][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Among them, one study was excluded by the poor data quality [45], so 19 publications were included in the final analysis.…”

Section: Literature Searching and Study Characteristicsmentioning

confidence: 99%

“…The details of the procedures of literature screening were shown in Figure 1. Among the 19 studies, 5 studies reported head and neck cancer without site information [7,33,36,39,43], 4 studies focused on oral and oropharyngeal cancer [30,32,40,44], 3 for tongue cancer [6,29,34], 3 for nasopharyngeal cancer [5,35,42], 2 for salivary gland cancer [37,38], 1 for hypopharyngeal cancer [41] and another one for tonsillar cancer [31]. The total number of patients included in the meta-analysis was 2,417, the mean sample size was 127 (ranges from 33 to 396).…”

Section: Literature Searching and Study Characteristicsmentioning

confidence: 99%

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WITHDRAWN: A meta-analysis of c-Met expression in head and neck cancer

Li¹,

Sun²,

Sun³

et al. 2017

Oncotarget

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Section: Literature Searching and Study Characteristicsmentioning

confidence: 99%

Section: Literature Searching and Study Characteristicsmentioning

confidence: 99%

WITHDRAWN: A meta-analysis of c-Met expression in head and neck cancer

Li¹,

Sun²,

Sun³

et al. 2017

Oncotarget

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“…The MET pathway has been shown to promote self-renewal and tumorigenicity in HNSCC stem-like cells (41) and pharmacologic selective inhibition of MET has been shown to lead to elimination of CSCs (42). Furthermore, MET was found to be associated with poor prognosis in patients with locally advanced p16-negative HNSCC who were treated with primary radiochemotherapy (43). In the current study, we have shown that MET overexpressing HPV16 DNA-negative HNSCC are associated with poor locoregional tumor control and increased distant metastases after PORT-C. Interestingly, Pennacchietti and colleagues showed that hypoxia activates the transcription of the MET proto-oncogene, that MET overexpression is associated with hypoxic areas of tumors and that MET inhibition prevents hypoxia-induced cell growth (44).…”

Section: Discussionmentioning

confidence: 99%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

117

143

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Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

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“…The description of the patients and creation of the tissue microarray have been previously described . Briefly, after approval from the William Beaumont Hospital Human Institutional Review Board (IRB# 2012‐013), 223 locally advanced HNSCC patients with long‐term follow‐up and treated with definitive chemoradiation were identified from our head and neck database.…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of MTOR expression in HPV positive and negative head and neck cancers treated by chemoradiation

et al. 2019

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Background: The mechanistic target of rapamycin (MTOR) plays a key role in regulating cell growth and metabolism and is commonly overexpressed in head and neck cancer (HNSCC). This study investigated the association of MTOR with clinical outcome in human papilloma virus (HPV) positive and negative HNSCC patients treated by chemoradiation. Methods: A tissue microarray (TMA) consisting of cores from 109 HNSCC patients treated by definitive chemoradiation was constructed and stained with antibodies against p16 and MTOR and expression correlated with clinicopathological features and clinical outcome. Results: MTOR varied widely between tumor cores and was not associated with HPV status or clinicopathological features. There was a positive correlation with pre-treatment FDG uptake.(P = .01). In HPV negative patients, MTOR predicted for shorter locoregional control (P = .02), diseases free survival (P = .02), and overall survival (P = .04).MTOR expression was not associated with outcome in HPV positive patients. Conclusions: Prognostic significance of MTOR expression depends on HPV status.

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c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head-and-Neck Squamous Cell Carcinoma Treated With Chemoradiation

Cited by 12 publications

References 0 publications

WITHDRAWN: A meta-analysis of c-Met expression in head and neck cancer

WITHDRAWN: A meta-analysis of c-Met expression in head and neck cancer

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Prognostic significance of MTOR expression in HPV positive and negative head and neck cancers treated by chemoradiation

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