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. 2023 Jun;14(3):205-223.
doi: 10.14740/wjon1595. Epub 2023 Jun 11.

Comprehensive Analysis Reveals the Potential Roles of Transcription Factor Dp-1 in Lung Adenocarcinoma

Yipeng Song  1 , Rongna Ma  2
Affiliations

Comprehensive Analysis Reveals the Potential Roles of Transcription Factor Dp-1 in Lung Adenocarcinoma

Yipeng Song et al. World J Oncol. 2023 Jun.

Abstract

Background: Transcription factor Dp-1 (TFDP1) was overexpressed and interacted with other genes to impact multiple signaling pathways in various human cancers. However, there is less research about the TFDP1 specific roles in lung adenocarcinoma (LUAD).

Methods: We first explored TFDP1 expression levels and relative diseases from a pan-cancer perspective using the ONCOMINE, TIMER, and Open Targets Platform databases. Then, we used UALCAN, GEPIA 2, TCGA-LUAD data, and Kaplan-Meier plotter to examine TFDP1 clinicopathological features and prognosis in LUAD patients. Genomic alterations and DNA methylation analysis were performed by cBioPortal and MethSurv, respectively. Then, we used a cancer single-cell state atlas (CancerSEA) to find TFDP1 functions at a single-cell resolution. LinkedOmics was used to find TFDP1 coexpressed genes, biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Then, Gene Set Cancer Analysis (GSCA) was used to examine the drug resistence of TFDP1 in LUAD.

Results: We found that TFDP1 was overexpressed in most human cancers and related to various diseases, including LUAD. Moreover, LUAD patients with high TFDP1 expression levels might be significantly associated with individual cancer stages and have a poor prognosis. Multivariate analysis revealed that the American Joint Committee on Cancer (AJCC) pathologic stage, AJCC stage T, and AJCC stage N were the independent prognostic factors. LUAD patients with TFDP1 alterations suggested poor overall survival (OS), and disease-free survival (DFS), while hypermethylation might lead to a good prognosis. TFDP1 and its coexpressed genes were enriched in multiple signaling pathways and biological processes involved in the cell cycle, spliceosome, and DNA replication. Furthermore, TFDP1 was strongly positively related to the half-maximal inhibitory concentration (IC50) values of multiple drugs.

Conclusions: In summary, TFDP1 was a possible biomarker and potential therapeutic target for LUAD patients.

Keywords: Lung adenocarcinoma; Omics analysis; Prognostic biomarker; TFDP1; Therapeutic target.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
TFDP1 expression in various types of human cancer and its relative diseases. (a) The difference of TFDP1 mRNA levels in cancer tissues and normal tissues (ONCOMINE). (b) The TFDP1 expression difference from the TIMER database. (c) The TFDP1 protein expression differences in the CPTAC database (UALCAN). (d) TFDP1-associated diseases obtained by Open Targets Platform. (***P < 0.001). TFDP1: transcription factor Dp-1; CPTAC: Clinical Proteomics Tumor Analysis Consortium.
Figure 2
Figure 2
Relationship of TFDP1 with the pathological stages of LUAD patients analyzed by UALCAN (a) and GEPIA 2 (b). (c) TFDP1 expression differences in the LUAD histological subtypes. (*P < 0.05, **P < 0.01, ***P < 0.001). TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 3
Figure 3
The TFDP1 prognosis in LUAD patients using the Kaplan-Meier plotter. (a)The OS curve of TFDP1 in LUAD. (b) The first progression (FP) curve of TFDP1 in LUAD. (c) The PPS curve of TFDP1 in LUAD. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma; OS: overall survival; PPS: post progression survival.
Figure 4
Figure 4
TFDP1 alterations in LUAD patients analyzed by cBioPortal and GeneMANIA. (a) Alteration frequencies of TFDP1 across various human cancers. (b) Alteration frequencies of RYR2, MUC16, TTN, ZFHX4, TP53, GRK1, LAMP1, RASA3, CSMD3, and ATP4B cooccurred with TFDP1 alterations in LUAD. (c) Summary of genetic alterations of TFDP1, ATP4B, RASA3, LAMP1, and GRK1 in LUAD. (d) The OS and (e) the DFS between TFDP1-altered and TFDP1-unaltered groups in LUAD patients. (f) Gene-gene interaction network of TFDP1 and its cooccurred genes. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma; OS: overall survival;DFS: disease-free survival.
Figure 5
Figure 5
The heatmap shows TFDP1 methylation levels at different CpG sites in LUAD patients (MethSurv). TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 6
Figure 6
Single-cell functional analysis of TFDP1 in LUAD (CancerSEA). (a) Relevance of TFDP1 across 14 functions in multiple human cancers. (b-f) The various functions were markedly associated with TFDP1 in LUAD. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 7
Figure 7
TFDP1 coexpressed genes in LUAD (LinkedOmics). (a) The volcano plot shows the TFDP1-related significantly coexpressed genes (Pearson test) in LUAD. (b) The heat map shows the top 50 positively TFDP1-correlated genes. (c) The heat map shows the top 50 negatively TFDP1-correlated genes. (d) Survival maps show the top 50 genes positively and negatively related to TFDP1, respectively. (e) Correlations between the top five positively TFDP1-correlated genes and TFDP1. (f) Correlations between the top five negatively TFDP1-correlated genes and TFDP1. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 7
Figure 7
TFDP1 coexpressed genes in LUAD (LinkedOmics). (a) The volcano plot shows the TFDP1-related significantly coexpressed genes (Pearson test) in LUAD. (b) The heat map shows the top 50 positively TFDP1-correlated genes. (c) The heat map shows the top 50 negatively TFDP1-correlated genes. (d) Survival maps show the top 50 genes positively and negatively related to TFDP1, respectively. (e) Correlations between the top five positively TFDP1-correlated genes and TFDP1. (f) Correlations between the top five negatively TFDP1-correlated genes and TFDP1. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 7
Figure 7
TFDP1 coexpressed genes in LUAD (LinkedOmics). (a) The volcano plot shows the TFDP1-related significantly coexpressed genes (Pearson test) in LUAD. (b) The heat map shows the top 50 positively TFDP1-correlated genes. (c) The heat map shows the top 50 negatively TFDP1-correlated genes. (d) Survival maps show the top 50 genes positively and negatively related to TFDP1, respectively. (e) Correlations between the top five positively TFDP1-correlated genes and TFDP1. (f) Correlations between the top five negatively TFDP1-correlated genes and TFDP1. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.
Figure 8
Figure 8
Gene set enrichment analysis of the genes coexpressed with TFDP1 in LUAD (LinkedOmics). (a) Biological process and (b) KEGG pathway analyses of TFDP1 in the TCGA cohort. (c) Chromosome segregation (normalized enrichment score (NES) = 2.4230, P < 0.001). (d) DNA replication (NES = 2.3660, P < 0.001). (e) Spindle organization (NES = 2.3299, P < 0.001). (f) Cell cycle checkpoint (NES = 2.2625, P < 0.001). (g) Negative regulation of cell cycle process (NES = 2.2039, P < 0.001). (h) Cell cycle (NES = 2.3389, P < 0.001). (i) DNA replication (NES = 2.1674, P < 0.001). (j) Fanconi anemia pathway (NES = 2.1372, P < 0.001). (k) Spliceosome (NES = 2.0545, P < 0.001). (l) Homologous recombination (NES = 2.0336, P < 0.001). TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma KEGG: Kyoto Encyclopedia of Genes and Genomes; FDR: false discovery rate.
Figure 8
Figure 8
Gene set enrichment analysis of the genes coexpressed with TFDP1 in LUAD (LinkedOmics). (a) Biological process and (b) KEGG pathway analyses of TFDP1 in the TCGA cohort. (c) Chromosome segregation (normalized enrichment score (NES) = 2.4230, P < 0.001). (d) DNA replication (NES = 2.3660, P < 0.001). (e) Spindle organization (NES = 2.3299, P < 0.001). (f) Cell cycle checkpoint (NES = 2.2625, P < 0.001). (g) Negative regulation of cell cycle process (NES = 2.2039, P < 0.001). (h) Cell cycle (NES = 2.3389, P < 0.001). (i) DNA replication (NES = 2.1674, P < 0.001). (j) Fanconi anemia pathway (NES = 2.1372, P < 0.001). (k) Spliceosome (NES = 2.0545, P < 0.001). (l) Homologous recombination (NES = 2.0336, P < 0.001). TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma KEGG: Kyoto Encyclopedia of Genes and Genomes; FDR: false discovery rate.
Figure 9
Figure 9
Drug sensitivity analysis. (a) The lollipop plot showing the TFDP1-drug pairs sensitivity in the GDSC database. (b) The lollipop plot showing the TFDP1-drug pairs sensitivity in the CTRP database. TFDP1: transcription factor Dp-1; GDSC: Genomics of Drug Sensitivity in Cancer; CTRP: Cancer Therapeutics Response Portal.
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