Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy

FNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients.MethodsWe determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III–IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis.ResultsThere were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5–49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2–100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71–22.06).ConclusionFNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival. (AU)

Correlation of the prognostic value of FNDC4 in glioblastoma with macrophage polarization.

BACKGROUND: Glioblastoma is among the most malignant tumors in the central nervous system and characterized by strong invasion and poor prognosis. Fibronectin type III domain-containing 4 (FNDC4) plays various important roles in the human body, including participating in cellular metabolism and inflammatory responses to cardiovascular diseases, influencing immune cells, and exerting anti-inflammatory effects; however, the role of FNDC4 in glioblastoma has not been reported. METHODS: In this study, bioinformatics databases, including TCGA, CGGA, GTEx, and TIMER, were used to analyze the differential expression of FNDC4 genes and cell survival, in addition to investigating its relationship with immune cell infiltration. Additionally, we overexpressed FNDC4 in glioblastoma cell lines U87 and U251 by lentiviral transfection and detected changes in proliferation, cell cycle progression, and apoptosis. Following collection of monocytes from the peripheral blood of healthy individuals and transformation into M0 macrophages, we performed flow cytometry to detect the polarizing effect of exogenous FNDC4, as well as the effect of FNDC4-overexpressing glioblastoma cells on macrophage polarization in a co-culture system. RESULTS: We identified that significantly higher FNDC4 expression in glioblastoma tissue relative to normal brain tissue was associated with worse prognosis. Moreover, we found that FNDC4 overexpression in U87 and U251 cells resulted in increased proliferation and affected the S phase of tumor cells, whereas cell apoptosis remained unchanged. Furthermore, exogenous FNDC4 inhibited the M1 polarization of M0 macrophages without affecting M2 polarization; this was also observed in glioblastoma cells overexpressing FNDC4. CONCLUSIONS: FNDC4 expression is elevated in glioblastoma, closely associated with poor prognosis, and promoted the proliferation of glioblastoma cells, affected the S phase of tumor cells while inhibiting macrophage polarization.

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy.

PURPOSE: FNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients. METHODS: We determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III-IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis. RESULTS: There were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5-49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2-100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71-22.06). CONCLUSION: FNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival.