The identification of novel independent prognostic markers is of paramount importance for the advancement of research, accuracy of preoperative diagnosis and improvement of survival rate in patients with laryngeal cancer.
Chromogranins are commonly used as markers of neuroendocrine tumors, including laryngeal tumors. A member of this family, the Secretogranin VGF (non-acronymic), a nerve growth factor inducible gene, has been shown to trigger epithelial-to-mesenchymal transition in lung adenocarcinoma, suggesting its potential utility as a marker for acquirement of tumor invasiveness. However, no data exist about the presence and role of VGF in laryngeal cancer.
Considering the role exerted by VGF in the regulation of cell survival and proliferation, the presence of this polypeptide in laryngeal tumors may represent a relevant factor to identify patients with poor prognosis in tumors of both neuroendocrine and, conceivably, epithelial origin.
The aim of this study is to potentially identify the Secretogranin VGF as a new marker of the active/proliferating status of the tumor, thus detecting neoplastic lesions with higher risk of tumor invasiveness also in non-neuroendocrine tumors.
Thirty patients with laryngeal cancer will be included in the study. Primary tumor tissue and healthy laryngeal tissue from the same patient will be collected during surgery. In addition, a blood sample will be collected pre- and post-operatively during follow up at 6 and 9 months and analyzed by Western blotting. The presence of VGF expression in patients samples will be evaluated by Real-time PCR analysis and the presence of the corresponding protein by immunohistochemistry/immunofluorescence and Western blot analysis.
The innovation of this research project is to address whether VGF can be considered an independent prognostic factor in laryngeal carcinomas, with the aim to achieve an appropriate diagnosis, a better management of follow-up and a potential target therapy.
This research project aims to obtain scientific evidence that in laryngeal carcinoma VGF might be useful to detect neoplastic lesions with higher risk of tumor invasiveness, thus helping in predicting the tumor malignancy and the risk to generate metastasis. While the presence of VGF in laryngeal tumors of neuroendocrine origin is quite foregone, the presence of this polypeptide in laryngeal non-endocrine tumors may represent a prognostic factor to identify high-risk patients, in view of the proliferative functions of VGF and the stringent correlation between its appearance and a poor survival in patients with endocrine and non-endocrine carcinomas.
The working plan is to investigate the expression of VGF as a tumor marker, additionally to the well-defined markers used to identify high grade squamous cell carcinoma and neuroendocrine laryngeal carcinomas, as vimentin and Chromogranin A, respectively.
Real-time PCR, immunohistochemistry/immunofluorescence and Western blot analysis will be applied to analyze the potential presence and the distribution of VGF positive cells in the neoplastic tissue and in peripheral blood samples to identify subpopulations of VGF-positive cells potentially contributing to the environmental changes associated with tumor aggressiveness and disease-free survival. In support to our hypothesis, literature data indicate that, at least in lung adenocarcinoma cells, VGF expression facilitates the resistance to the antitumor therapy, as well as cancer dissemination, the growth of which is dependent on VGF expression.
To confirm the deleterious role exerted by VGF in neuroendocrine tumors, it has been demonstrated that VGF silencing resensitized the lung adenocarcinoma mutated cells to a therapy-sensible phenotype, thus suggesting its potential utility as a biomarker and therapeutic target in lung adenocarcinoma (Hwang et al., 2017).
Interestingly, although either VGF, Chromogranin A or Chromogranin B are highly expressed in neuroendocrine tumors, only VGF levels correlate with resistance and with a poor survival in patients with endocrine and non-endocrine lung carcinomas.
The innovation of this research project is to address whether VGF can be considered an independent prognostic factor in laryngeal carcinomas, with the aim to achieve an appropriate diagnosis and a potential target therapy.