FAM72 serves as a biomarker of poor prognosis in human lung adenocarcinoma

Abstract

FAM72A-D promote the self-renewal of neural progenitor cells. There is accumulating evidence that FAM72 promotes tumorigenicity. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of FAM72A-D in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between FAM72 and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, GEPIA, Metascape, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, FAM72 expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high FAM72 expression levels were correlated with a poor OS in LUAD. Additionally, FAM72 expression was independently associated with OS through a multivariate Cox analysis. GO and GSEA revealed enrichment in mitotic nuclear division and cell cycle. Moreover, high FAM72 expression was associated with poor survival. An analysis of immune infiltration showed that FAM72 is correlated with immune cell infiltration. Finally, we found that the methylation level was associated with prognosis in patients with LUAD. In summary, these results indicate that FAM72 is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.

Keywords: FAM72 family; The Cancer Genome Atlas; immune infiltration; lung adenocarcinoma; prognosis.

Figure 1

FAM72A-D expression levels in LUAD from TCGA data. (A–D) The expression levels of FAM72A-D in LUAD and normal tissue; (E) The correlation between FAM72A-D members; (F) Receiver operating characteristic analysis (ROC) of FAM72A-D in LUAD. (*P < 0.05, **P < 0.01, ***P < 0.001).

Figure 2

The prognostic value of FAM72A-D expression in LUAD. (A–D) Survival curves of OS from TCGA data (n = 497); (E–H) Survival curves of OS from GSE 13213, GSE30219, GSE41271 and GSE50081 data (n = 117, 85, 181, and 127, respectively).

Figure 3

Nomogram for predicting the probability of 1-, 3- and 5-year OS for LUAD patients. (A–D) A nomogram that integrates FAM72A-D and other prognostic factors in LUAD from TCGA data.

Figure 4

Calibration curve for predicting the probability of 1-, 3- and 5-year OS for LUAD patients. (A–D) The calibration curve of the nomogram in LUAD from TCGA data.

Figure 5

Functional enrichment of FAM72A-D in LUAD. (A–D) Gene ontology (GO) enrichment analysis of FAM72A-D and its co-expression genes in Metascape. The GO enriched terms are colored by p-value, where terms containing more genes tend to have more significant p-value.

Figure 6

An interactive network of the top enrichment terms. (A–D) It is colored by cluster-ID. Distinct colors are various enrichment pathways of FAM72A-D correlated genes.

Figure 7

The top 20 pathways were differentially enriched according to the level of NES in FAM72A-D related LUAD. (A–D) The enrichment plot was obtained from the gene set enrichment analysis (GSEA).

Figure 8

The functional pathways and gene alteration of FAM72A-D in LUAD. (A) Several pathways were enriched in FAM72A-D related LUAD, including the proliferation, EGFR signaling, undifferentiated cancer, lung cancer poor survival and cell cycle; (B, C) Genetic alteration in FAM72A-D and its association with OS of LUAD patients.

Figure 9

The methylation of FAM72A/B/D in LUAD. (A–C) The visualization between the methylation level and the FAM72A/B/D expression; (D) The Kaplan-Meier survival of the promoter methylation of FAM72B.