Expression and prognosis analyses of the fibronectin type-III domain-containing (FNDC) protein family in human cancers: A Review

Abstract

Despite advancements in early detection and treatment, cancer continues to pose a threat to human health and is the leading cause of death worldwide. According to recent research, the fibronectin type-III domain-containing (FNDC) protein family has been implicated in several different human disorders. However, little is known regarding their expression and prognostic significance in most human malignancies. We carried out a thorough cancer vs. normal expression study using the Oncomine and Tumor Immune Estimation Resource (TIMER) databases, as well as a prognostic evaluation using the Kaplan-Meier (KM) plotter and PrognoScan databases. Oncomine revealed that the mRNA expression levels of FNDC1, FNDC3A, and FNDC3B were higher in most malignancies than in normal tissues, but the mRNA expression levels of FNDC4, FNDC5, FNDC7, and FNDC8 were downregulated in most cancers when compared with normal tissues. In survival analyses based on KM Plotter and PrognoScan, all members of the FNDC family displayed significant correlations with survival outcomes in breast, gastric, and ovarian cancers. Furthermore, the whole FNDC family, except for FNDC7 and FNDC8, was found to have substantial predictive effects in lung adenocarcinoma, but not in squamous cell lung cancer. In addition, potential connections between several FNDC family members and survival results in liver and colorectal malignancies were discovered in this study. One or more members of the FNDC family demonstrated statistically significant differences in expression between cancer and normal tissues, suggesting that they could be used as prognostic biomarkers for specific cancers.

Figure 1.

The mRNA expression levels of the FNDC family in human cancers. The number of analyses that meet the thresholds was shown in the colored cells. The gene rank determines the cell color, which represents the importance of genes in cancer. The red and blue indicate over-expressed and under-expressed respectively, and the brighter red or blue implies a gene with a higher or lower level of expression that is more statistically significant. FNDC = fibronectin type-III domain-containing, KM = Kaplan-Meier.

Figure 2.

Survival curves of the FNDC family in breast cancer. (a-h): prognosis analysis of the FNDC family obtained from the KM plotter database. (i-j): prognosis analysis of FNDC4, FNDC7 and FNDC8 obtained from the KM plotter database, respectively. DMFS = distant metastasis free survival, DSS = disease specific survival, FNDC = fibronectin type-III domain-containing, KM = Kaplan-Meier, OS = overall survival, RFS = relapse free survival.

Figure 3.

Survival curves of the FNDC family in lung adenocarcinoma. Survival analyses of FNDC3A (a, d), FNDC3B (e, f), FNDC4 (g, h), FNDC5 (i, j) and FNDC6 (k, l) were downloaded from the KM plotter database. Survival analyses of FNDC1 (b, c) were downloaded from the PrognoScan database. FNDC = fibronectin type-III domain-containing, FP = first progression, KM = Kaplan-Meier, OS = overall survival, RFS = relapse free survival.

Figure 4.

Survival curves of the FNDC family in gastric cancer. Survival analyses of FNDC1 (a), FNDC3A (b), FNDC3B (c), FNDC4 (d), FNDC5 (e), FNDC6 (f), FNDC7 (g) and FNDC8 (h) were obtained from the KM plotter database. FNDC = fibronectin type-III domain-containing, KM = Kaplan-Meier, OS = overall survival.

Figure 5.

Survival curves of the FNDC family in liver cancer. Survival analyses of FNDC1 (a, b), FNDC3A (c, d), FNDC3B (e), FNDC5 (g, h), FNDC6 (i), FNDC7 (j) and FNDC8 (k) were obtained from the KM plotter database. DSS = disease specific survival, FNDC = fibronectin type-III domain-containing, KM = Kaplan-Meier, OS = overall survival, PFS = progression free survival, RFS = relapse free survival.

Figure 6.

Survival curves of the FNDC family in ovarian cancer. Survival analyses of FNDC1 (a, b), FNDC3A (c, d), FNDC3B (e), FNDC5 (g, h), FNDC6 (i, j), FNDC7 (k, l) and FNDC8 (m, n) were obtained from the KM plotter database. Survival analysis of FNDC4 (f) was obtained from the PrognoScan database. FNDC = fibronectin type-III domain-containing, KM = Kaplan-Meier, OS = overall survival, PFS, progression free survival.

Figure 7.

Survival curves of the FNDC family in colorectal cancer. Survival analyses of FNDC1 (a, b, c), FNDC3B (d), FNDC5 (e, f), FNDC7 (g, h) and FNDC8 (i) were obtained from the KM plotter database. DFS = disease free survival, DSS = disease specific survival, FNDC = fibronectin type-III domain-containing, OS = overall survival.