Study Identifies FGFR3 as Biomarker for Superior Outcomes in NSCLC

New research has identified a potential new biomarker for overall survival (OS) in patients with non–small cell lung cancer (NSCLC).

The study, published in Journal of Thoracic Disease, found that the expression of fibroblast growth factor receptor 3 (FGFR3) was associated with patient outcomes.

Study authors noted that FGFR3 is involved in a variety of processes, including cell proliferation, differentiation, and migration. Previous studies have identified alterations in FGFR3 in cases of NSCLC, but they have come to varying conclusions about the frequency of the alterations.

“To date, no data are available on the distribution rates for FGFR3 expression and mutation, its relation to clinicopathological characteristics, and clinical outcomes in NSCLC,” they explained.

The authors decided to use immunohistochemistry to evaluate FGFR3 protein expression in 116 tissue samples from patients with NSCLC and then use Sanger sequencing to probe the mutation status of exons 7, 10, and 15. They then analyzed those results to see how they correlated with outcomes in the 86 patients for whom complete clinical data were available.

Among the 86 cases included in the analysis, FGFR3 was immunoreactive in 26 cases. FGFR3 was positively expressed in 84.6% of the 39 adenocarcinoma cases in the data set, but it was only positively expressed in 15.4% of the 47 squamous cell carcinoma cases.

In terms of mutations, the investigators found a low frequency rate. Mutations were present in just 2 of 72 cases—1 adenocarcinoma case and 1 squamous cell carcinoma case—and both had the T450M mutation. Further, both were novel mutations in exon 10; no mutations were found in exons 7 or 15.

When investigators compared their findings to patient outcomes, they found high FGFR3 expression was associated with better OS and better disease-free survival (DFS). Patients in the high-FGFR3 group were also more likely to be female, nonsmokers, and at an earlier T stage.

“The results of the survival analysis revealed the patients with high FGFR3 expression levels had better OS, which suggests that lower or reduced FGFR3 expression levels may enhance NSCLC progression, while FGFR3 overexpression may attenuate NSCLC progression,” they wrote.

The investigators noted that FGFR3 expression has been linked with a poorer prognosis in other types of cancer, including muscle-invasive bladder carcinoma and breast cancer, and that there are a number of potential reasons for the apparent contradiction.

“In the present study, we only included the patients with surgically resectable NSCLC at the I-IIIA stage, and the favorable prognostic role of FGFR3 may only occur in patients with early-stage NSCLC,” they said.

The authors added that their rate of FGFR3 expression was significantly higher among patients with adenocarcinoma, and patients with high FGFR3 expression tended to have higher epidermal growth factor receptor (EGFR) mutation rates. Thus, patients with high FGFR3 expression were more likely to be treated with EGFR tyrosine kinase inhibitors.

“Therefore, it is speculated that patients with high FGFR3 expression have longer OS and DFS and are closely associated with higher EGFR mutations,” they said. “However, the mechanistic actions still need to be further investigated.”

The authors cautioned that their study is preliminary in nature and is based on a single center in a single country, and thus may not be generalizable to the entire NSCLC population. Still, they said their initial findings suggest FGFR3 may be a useful biomarker in this cancer type.

Reference

Lin YE, Long HD, Chen CC, et al. High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population. J Thorac Dis. 2023;15(1):101-111. doi:10.21037/jtd-22-1523