Fibroblast Growth Factor 9 Correlation with Lymphatic and Vascular Invasion in Colorectal Cancer

Abstract

Background: Fibroblast growth factor 9 (FGF9) or Glia activating factor (GAF) is categorized in the paracrine class of the FGF family, which is involved in various cancer development and progressions. Interestingly, the invasion role of FGF9 in colorectal cancer (CRC) was not clarified up to now. Objectives: In the present investigation, the lymphatic and vascular invasion characteristic of FGF9 was figured out in fresh frozen (FF) tissue samples and paired Formalin-fixed, paraffin-embedded (FFPE) tissues. Methods: The present invasion study according to FGF9 expression evaluation was performed on 80 cancerous resected fresh tissues and 40 paired paraffined block specimens parallel with 80 adjacent non-tumoral tissue samples. RNA extraction and cDNA synthesis were performed; qRT-PCR at mRNA level was applied. FGF9 expression correlation with clinical parameters was defined by the Mann-Whitney U-test. ROC curve and Kaplan-Meier analyses were designed to show the value of prognostic biomarker of FGF9. Results: Accordingly, 52% of fresh tissue samples and 51% of FFPE specimens were upregulated in comparison with corresponding normal tissues. A significant correlation was seen between FGF9 expression level and tumor stage (P < 0.0017, P < 0.03), lymph node metastasis (P < 0.001, P < 0.047), and vascular invasion (P < 0.004, P < 0.047) in fresh tissue samples and paraffined blocks, respectively. ROC was created to distinguish stage I and II from III and IV in FF and FFPE samples, respectively (P < 0.002, P < 0.031). Likewise, the AUC evaluation in both fresh and paraffined samples was similar. The overall survival was lower in 3 years of follow-up in patients with CRC with overexpression of FGF9 (P < 0.02). Conclusions: Altogether, it can be deduced that lymphatic and vascular invasion correlated with FGF9 upregulation since FGF9 can be used as an effective prognostic biomarker according to pathologic results even in paraffined block samples or FF tissue specimens in CRC.