World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 14, Number 3, June 2023, pages 205-223

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

Figures

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. 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. 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. 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. The heatmap shows TFDP1 methylation levels at different CpG sites in LUAD patients (MethSurv). TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma.

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. 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. 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. 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.

Tables

**Table 1.** Univariate and multivariate Cox regression analysis in LUAD
Variables	Univariate analysis			Multivariate analysis
Variables	N	Hazard ratio	P value	Hazard ratio	P value
*P < 0.05. TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma; AJCC: American Joint Committee on Cancer.
TFDP1
Low	377	Reference
High	142	1.43 (1.05 - 1.94)	0.023*	1.29 (0.94 - 1.76)	0.117
AJCC pathologic stage			< 0.001*
I	289	Reference
II	124	2.25 (1.58 - 3.21)	< 0.001*	1.16 (0.63 - 2.14)	0.625
III	80	3.52 (2.42 - 5.11)	< 0.001*	1.62 (0.68 - 3.86)	0.274
IV	26	3.72 (2.16 - 6.43)	< 0.001*	2.32 (1.16 - 4.65)	0.017*
AJCC stage T			< 0.001*
T1	172	Reference
T2	280	1.50 (1.05 - 2.13)	0.025*	1.23 (0.84 - 1.77)	0.268
T3	46	2.94 (1.75 - 4.94)	< 0.001*	2.30 (1.24 - 4.28)	0.008*
Other	21	3.49 (1.91 - 6.39)	< 0.001*	1.67 (0.81 - 3.43)	0.162
AJCC stage N			< 0.001*
N0	340	Reference
N1	95	2.26 (1.60 - 3.18)	< 0.001*	1.87 (1.06 - 3.30)	0.032*
N2	70	3.11 (2.14 - 4.53)	< 0.001*	1.82 (0.82 - 4.03)	0.138
Other	14	1.23 (0.45 - 3.34)	0.690	0.88 (0.31 - 2.55)	0.818

**Table 2.** The Significant Correlation of TFDP1 Methylation at Different CpG Sites With the Prognosis in LUAD
CpG sites	HR	CI	P value	UCSC_RefGene_Group	Relation_to_UCSC_CpG_Island
TFDP1: transcription factor Dp-1; LUAD: lung adenocarcinoma; HR: hazard ratio; CI: confidence interval.
cg10439691	1.525	(1.104; 2.105)	0.010365787	Body	Island
cg11976193	1.435	(1.045; 1.97)	0.025736416	Body	N_Shelf
cg01595804	0.678	(0.475; 0.969)	0.032998214	Body	Island
cg26355737	0.699	(0.499; 0.978)	0.03671796	Body	N_Shore