Prognostic effects of the expression of inhibitor of DNA-binding family members on patients with lung adenocarcinoma

Abstract

The basic helix-loop-helix (bHLH) transcription factors are negatively regulated by inhibitor of DNA-binding (ID) proteins. Several studies have demonstrated that ID family proteins are dysregulated in a variety of cancer types, including in lung adenocarcinoma (LUAD). In current study, the prognostic value of ID family members was evaluated by investigating publicly accessible databases, including Oncomine, Kaplan-Meier plotter, UALCAN and the Human Protein Atlas. It was observed that the mRNA expression of all ID members was downregulated in LUAD tumor tissues compared with those in normal tissues according to the Oncomine and UALCAN databases. Additionally, increased mRNA expression levels of ID2 and ID1 were associated with improved and poorer survival time, respectively. Notably, ID3 and ID4 expression was not associated with survival in patients with LUAD. At the protein level, high ID2 significantly predicted an improved survival outcome while high ID1 is associated with shorter survival time. Thus, the results indicate that the ID proteins, particularly ID2, exhibit significant prognostic value in LUAD. More studies are required to elucidate the underlying molecular mechanisms behind the role of the ID family in the development of LUAD.

Keywords: inhibitor of DNA binding protein family members; lung adenocarcinoma; prognosis.

Figure 1.

mRNA expression patterns of IDs in different types of human malignancy. mRNA expression of ID family members (cancer vs. normal tissue) was analyzed with the Oncomine database. Red indicates high expression and blue indicates low expression of the target gene. The P-value threshold was maintained to be 0.01. The number in each cell represents the number of analyses that meets this threshold. Gene rank was analyzed by the percentile of the target gene in the top of all genes measured in each study. The cell color was determined by the gene rank percentile for the analyses within the cell. P<0.01 and fold-change >2 were used to establish the threshold. ID, inhibitor of DNA binding; CNS, central nervous system.

Figure 2.

mRNA expression of the ID family members in LUAD and normal tissues from the TCGA database. mRNA expression levels of (A) ID1, (B) ID2, (C) ID3 and (D) ID4 in LUAD compared with those in normal tissues. Significant difference between groups was assessed using the unpaired two-sample Student's t-test. The two comparison groups are normal vs. primary tumor. All data are presented as the mean ± standard deviation (SD). All groups are different groups of patients or normal controls. *P<0.05. ID, inhibitor of DNA binding; TCGA, The Cancer Genome Atlas; LUAD, lung adenocarcinoma.

Figure 3.

Association between the gene expression levels of ID family proteins with cancer stage or smoking status, using data from TCGA. mRNA expression levels of (A) ID1, (B) ID2, (C) ID3 and (D) ID4 in normal tissues compared with those in tissues at various different cancer stages. (E) ID1, (F) ID2, (G) ID3 and (H) ID4 mRNA expression levels in normal tissues normalized to patient status. Data are presented as the mean ± standard deviation (SD). One-way ANOVA was used to test differences among groups. If statistical significance was obtained through ANOVA (P<0.05), Tukey's post-hoc test was used to make multiple comparisons. P<0.05 was considered to indicate a statistically significant difference. ID, inhibitor of DNA binding; TCGA, The Cancer Genome Atlas; LUAD, lung adenocarcinoma.

Figure 4.

Genetic analysis of the prognostic values of the ID family members in patients with LUAD. Kaplan-Meier overall survival time estimates for (A) ID1, (B) ID2, (C) ID3 and (D) ID4 mRNA levels. P<0.05 was considered to indicate a statistically significant difference. ID, inhibitor of DNA binding; LUAD, lung adenocarcinoma; HR, hazard ratio.

Figure 5.

Proteomic analysis of the prognostic values of the ID family members in LUAD. Kaplan-Meier overall survival estimates for (A) ID1, (B) ID2, (C) ID3 and (D) ID4 protein levels. The Log-rank was used to compare the difference between survival time. P<0.05 was considered to indicate a statistically significant difference. ID, inhibitor of DNA binding; TCGA, The Cancer Genome Atlas; LUAD, lung adenocarcinoma.