Distinct prognostic value of dynactin subunit 4 (DCTN4) and diagnostic value of DCTN1, DCTN2, and DCTN4 in colon adenocarcinoma

Figures & data

Figure 1 (A) Study of enriched GO terminology and KEGG pathways for DCTN genes assessed by DAVID; (B) DCTN gene interaction networks among selected genes generated by GeneMANIA; (C) STRING physical and functional connections of DCTN genes.

Abbreviations: DAVID, Database for Explaining, Visualization, and Integrated Discovery; DCTN, dynactin; ER, endoplasmic reticulum; GeneMANIA, Gene Multiple Association Network Integration Algorithm; GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; MHC, major histocompatibility complex; STRING, Search Tool for the Retrieval of Interacting Genes/Proteins.

Figure 2 (A) Pearson’s correlation coefficients for DCTN gene expression levels, *P<0.001; (B) scatterplots for DCTN gene family expression levels in TCGA.

Abbreviations: DCTN, dynactin; TCGA, The Cancer Genome Atlas.

Figure 3 MERAV boxplots of expression of DCTN family in normal tissues and tumor-bearing tissues.

Note: Boxplots are shown for the expression levels of (A) DCTN1; (B) DCTN2; (C) DCTN3; (D) DCTN4; (E) DCTN5; and (F) DCTN6.

Abbreviations: DCTN, dynactin; MERAV, Metabolic gEne RApid Visualizer.

Figure 4 ROCs of six DCTN genes, showing differences between COAD tissue and adjacent normal colon tissue.

Note: ROCs of six prognostic differentially expressed miRNAs: (A) DCTN1; (B) DCTN2; (C) DCTN3; (D) DCTN4; (E) DCTN5; and (F) DCTN6.

Abbreviations: COAD, colon adenocarcinoma; DCTN, dynactin; ROC, receiver operating characteristics.

Table 1 Demographic and clinical data for 438 COAD patients

Variable	Patients (n=438)	No. of events (%)	MST (days)	HR (95% CI)	Log-rank P-value
Gender					0.545
Male	234	54 (23.1)	2,475	Ref.
Female	204	44 (22.6)	N/A	1.131 (0.759–1.686)
Age (years)					0.114
≥65	168	29 (17.3)	2,475	Ref.
<65	268	116 (25.4)	N/A	1.420 (0.919–2.194)
Tumor stage					<0.001
Advanced	187	62 (33.2)	1,711	Ref.
Early	240	31 (12.9)	3,042	0.323 (0.210–0.498)
Missing	11
Tumor stage					<0.001
IV	61	31 (51.8)	858	Ref.
I	73	4 (5.5)	N/A	0.089 (0.031–0.251)
II	167	27 (16.2)	2,821	0.198 (0.118–0.335)
III	126	31 (24.6)	N/A	0.360 (0.218–0.596)
Missing

Abbreviations: COAD, colon adenocarcinoma; MST, median survival time; N/A, not available.

Table 2 Prognostic survival analysis according to high or low expression of DCTN family genes

Gene	Patients (n=438)	No. of events (%)	MST (days)	Crude HR (95% CI)	Crude P-value	Adjusted HRa(95% CI)	Adjusted P valuea
DCTN1					0.131		0.446
Low	219	43 (19.6)	3,042	Ref.		Ref.
High	219	55 (25.1)	2,134	0.734 (0.492–1.096)		0.851 (0.563–1.288)
DCTN2					0.231		0.340
Low	219	56 (25.6)	2,475	Ref.		Ref.
High	219	42 (19.2)	N/A	0.783 (0.525–1.169)		1.222 (0.810–1.844)
DCTN3					0.649		0.594
Low	219	49 (22.4)	2,821	Ref.		Ref.
High	219	49 (22.4)	2,475	1.097 (0.737–1.632)		1.118 (0.741–1.686)
DCTN4					0.009		0.042
Low	219	61 (25.1)	1,910	Ref.		Ref.
High	219	37 (51.5)	N/A	0.581 (0.386–0.874)		0.650 (0.429–0.985)
DCTN5					0.958		0.701
Low	219	51 (23.3)	3,042	Ref.		Ref.
High	219	47 (21.5)	2,532	1.011 (0.677–1.508)		0.922 (0.611–1.393)
DCTN6					0.128		0.764
Low	219	54 (24.7)	1,910	Ref.		Ref.
High	219	44 (20.1)	2,821	0.733 (0.492–1.093)		0.938 (0.618–1.424)

Notes:

a Adjusted for tumor stage. Bold figures indicate statistically significance.

Abbreviations: DCTN, dynactin; MST, median survival time.

Figure 5 Prognostic graphs of DCTN expression for overall survival.

Note: Kaplan–Meier survival curves for complete COAD patients according to expression of (A) DCTN1; (B) DCTN2; (C) DCTN3; (D) DCTN4; (E) DCTN5; and (F) DCTN6 (n=438).

Abbreviations: COAD, colon adenocarcinoma; DCTN, dynactin.

Figure 6 Nomogram for the relations hip between medical data and risk score.

Abbreviation: DCTN, dynactin.

Figure 7 GSEA outcomes achieved for KEGG pathway analysis for higher and lower levels of expression of DCTN4, using gene set c2.

Note: (A) Metastasis; (B) cancer relapse tumor sample; (C) colon cancer recurrence; (D) metastasis; (E) EIF pathway; (F) metastasis; (G) inhibited invasion; (H) oncogenesis; (I) cell cycle S.

Abbreviations: DCTN, dynactin; EIF, eukaryotic initiation factor; ES, enrichment score; FDR, false discovery rate; GSEA, Gene Set Enrichment Analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes; NES, normalized enrichment score; NOM, nominal.

Figure 8 Pearson’s correlations among DCTN4 and possible associated COAD gene cohort of TCGA.

Note: An absolute value of the correlation coefficient >0.4 was considered to be highly correlated.

Abbreviations: COAD, colon adenocarcinoma; DCTN, dynactin; TCGA, The Cancer Genome Atlas.

Figure 9 Analysis of GO terms that are enriched and KEGG pathways for DCTN4 and the linked COAD gene cohort of TCGA obtained using DAVID.

Notes: Outcomes of GO analysis of functional enrichment: (A) BP outcomes; (B) CC outcomes; (C) MF outcomes; (D) KEGG outcomes. *P<0.001.

Abbreviations: BP, biological process; CC, cellular component; CDK, cyclin-dependent kinase; COAD, colon adenocarcinoma; DAVID, Database for Annotation, Visualization, and Integrated Discovery; DCTN, dynactin; GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAPK, mitogen-activated protein kinase; MF, molecular functionality; NAFLD, nonalcoholic fatty liver disease; NF, nuclear factor; RIG-I-like receptor, retinoic acid-inducible gene-I-like receptor; TCGA, The Cancer Genome Atlas.

Figure 10 GO analysis of functional enrichment by BiNGO for all the correlated genes.

Note: (A) BP outcomes; (B) CC outcomes; and (C) MF outcomes of GO analysis of functional enrichment by BiNGO.

Abbreviations: BiNGO, Biological Networks Gene Ontology; BP, biological process; CC, cellular component; DCTN, dynactin; ER, endoplasmic reticulum; GO, gene ontology; MF, molecular function; MLL, myeloid/lymphoid leukemia; SRP, signal recognition particle; TFIIH, transcription factor II H.

Figure 11 Gene contact networks between DCTN4 and potential-linked COAD gene cohort of TCGA generated by GeneMANIA.

Abbreviations: COAD, colon adenocarcinoma; DCTN, dynactin; GeneMANIA, Gene Multiple Connection Network Integration Algorithm; TCGA, The Cancer Genome Atlas.

Figure 12 STRING connections with functional and physical DCTN4 and correlated genes.

Abbreviations: DCTN, dynactin; STRING, The Search Tool for the Retrieval of Interacting Genes/Proteins.