FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma

Abstract

Objective: The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). Methods: FGFR4 immunohistochemistry and FGFR4/CEN5q FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. FGFR4 genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy. Results: The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The FGFR4 gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the FGFR4 Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, FGFR4 gene copy numbers and FGFR4 genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC. Conclusion: FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC.

Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104

“…FGFR4, the direct receptor of FGF19 and predominately expressed in liver tissues, was reported to be highly expressed in oral and oropharyngeal squamous cell carcinoma with a frequent Gly388Arg SNP [19]. Similar findings were reported in intrahepatic cholangiocarcinoma [20], colorectal cancer [21], and hepatocellular carcinoma [22].…”

Fibroblast Growth Factor 19–Mediated Up‐regulation of SYR‐Related High‐Mobility Group Box 18 Promotes Hepatocellular Carcinoma Metastasis by Transactivating Fibroblast Growth Factor Receptor 4 and Fms‐Related Tyrosine Kinase 4

“…Recently, FGF19‐FGFR4 has drawn increasing attention in carcinogenesis. Previous research has found that FGFR4 is overexpressed in multiple tumors, such as breast cancer, pancreatic carcinomas, and oral squamous cell carcinoma . The high levels of FGFR4 in nasopharyngeal carcinoma and CRC contributed to tumor cell proliferation and metastasis .…”

Dissecting the Role of the FGF19-FGFR4 Signaling Pathway in Cancer Development and Progression

“…Particularly, FGFR4 expression was significantly upregulated in most liver cancer cases, and enhanced FGF19-FGFR4 signaling is linked to HCC progression, metastasis, and poor survival (Sawey et al, 2011). Although high expression of FGFR4 was observed in OPSCC and pancreatic cancer, FGFR4 does not show prognostic significance in these cancers (Motoda et al, 2011;Koole et al, 2015).…”

“…FGF19 binds to FGFR4 and activates GSK3β-Nrf2 signaling cascade to exert cytoprotective role against ER stress in HCC . It has been reported that both rearranged distal enhancement regions and point mutations in the proximal promoter region might cause FGFR4 overexpression (Koole et al, 2015). Moreover, inhibition of miRNAs targeting FGFR4 or aberrant long noncoding RNA (lncRNA) expression leads to FGFR4 overexpression (Masaru, 2016).…”