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Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer

  • Authors:
    • Wenqi Zhang
    • Rongrong Zhang
    • Mengxuan Jia
    • Shuting Lan
    • Fangyuan Liu
    • Qin Jin
    • Liya Su
    • Gang Liu
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, Clinical Medicine Research Centre, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 145
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    Published online on: February 25, 2026
       https://doi.org/10.3892/ol.2026.15498
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Abstract

Colorectal cancer (CRC) remains one of the most common and lethal malignancies worldwide, with limited effective biomarkers for predicting prognosis and guiding immunotherapy response. The present study aimed to investigate the potential of DDB1‑ and CUL4‑associated factor 13 (DCAF13) as a biomarker for CRC. Bioinformatics analyses were performed using public datasets from The Cancer Genome Atlas and Gene Expression Omnibus; ESTIMATE, CIBERSORT, immune checkpoint, TIDE score and Kaplan‑Meier survival analyses were performed to assess the prognostic value and implications of DCAF13 expression in CRC. In silico findings were validated through immunohistochemistry (IHC), in vitro cell‑based assays and transcriptomic analysis. Increased DCAF13 expression levels were associated with reduced overall survival in patients with CRC based on the bioinformatics analysis, and this was validated using samples from patients using IHC. Immune profiling demonstrated an increased infiltration of M0 and M1 macrophages, activation of mast cells, neutrophils and CD4+ memory T cells in the DCAF13‑high expression group compared with the DCAF13‑low expression group. DCAF13 expression was correlated with immune modulators and checkpoint genes. High DCAF13 expression was associated with lower TIDE scores. In vitro assays and transcriptomic analyses confirmed the pro‑tumourigenic effects of DCAF13, which demonstrated roles in regulating cell proliferation, migration, clonogenicity, adhesion, metastasis, epithelial‑to‑mesenchymal transition and homologous recombination in CRC cells. The present study demonstrated that DCAF13 was upregulated in CRC and served a role in tumour progression, thus providing novel insights into the pro‑tumourigenic functions of DCAF13 and its potential as a critical regulator in CRC.
View Figures

Figure 1

DCAF13 is upregulated in pan-cancer
dataset and involved in multiple biological processes. (A)
Functional states of DCAF13 and association with 15 different
cancer types, as analysed using the CancerSEA database. (B)
Expression levels of DCAF13 across various cancer types, based on
data from the TCGA database and analysed using the Tumour Immune
Estimation Resource tool. (C) Differential expression of DCAF13
between CRC and NC tissues in the TCGA cohort. (D) Differential
expression of DCAF13 between CRC and NC tissues in the GSE40967
validation dataset. (E) KM survival analysis comparing high- and
low-expression groups of DCAF13 in the TCGA cohort. (F) KM survival
analysis comparing high- and low-expression groups of DCAF13 in the
GSE40967 validation dataset. *P<0.05, **P<0.01 and
***P<0.001. For box plots, the centre line indicates the median,
the box represents the interquartile range and the whiskers
represent data dispersion. CRC, colorectal cancer; DACF13, DDB1 And
CUL4 Associated Factor 13; TCGA, The Cancer Genome Atlas; KM,
Kaplan-Meier; HR, hazard ratio; NC, normal control.

Figure 2

Distribution of ESTIMATE scores and
analysis of TIICs by CIBERSORT. (A) The stromal scores of DCAF13
were calculated using the ESTIMATE method in the TCGA cohort. (B)
The immune scores of DCAF13 were calculated using the ESTIMATE
method in the TCGA cohort. (C) Bar chart depicting the proportion
of 22 TIIC types in the TME of CRC. (D) Boxplot comparing the
distribution of 22 TIICs in the TME of CRC between high- and
low-DCAF13 expression groups. Red labels indicate immune cell
subtypes showing statistically significant differences between the
high and low DCAF13 expression groups. *P<0.05, **P<0.01,
***P<0.001 and ****P<0.0001. CRC, colorectal cancer; DACF13,
DDB1- and CUL4-associated factor 13; TCGA, The Cancer Genome Atlas;
TIIC, tumour-infiltrating immune cells; TME, tumour
microenvironment.

Figure 3

Correlation between DCAF13 and immune
checkpoints and immune checkpoint gene analysis. (A) Correlation
between DCAF13 expression and BTLA. (B) Correlation between DCAF13
expression and LAG-3. (C) Correlation between DCAF13 expression and
SIRPα. (D) Correlation between DCAF13 expression and VISTA. (E)
Correlation analysis between different types of cancer, including
CRC, and 122 immunomodulators, including chemokines, receptors, MHC
molecules and immunostimulators. *P<0.05. DACF13, DDB1- and
CUL4-associated factor 13; BTLA, B and T lymphocyte attenuator;
LAG-3, lymphocyte-activating 3; SIRPα, signal regulatory protein α;
VISTA, V-domain Ig suppressor of T-cell activation.

Figure 4

Correlation between DCAF13 expression
and TIDE Scores. (A) TIDE score in high- vs. low-DCAF13 expression
groups. (B) T-cell dysfunction score in high- vs. low-DCAF13
expression groups. (C) T-cell exclusion score in high- vs.
low-DCAF13 expression groups. (D) MSI score in high- vs. low-DCAF13
expression groups ****P<0.0001. ns, not significant; DACF13,
DDB1- and CUL4-associated factor 13; MSI, microsatellite
instability.

Figure 5

Expression of DCAF13 in CRC
tissues/cells and survival analysis of patients with CRC. (A)
Representative immunohistochemical staining results of DCAF13 in
normal colon and CRC tissues. Scale bar, 100 mm. (B) Overall
survival rates in patients with CRC included in the present study.
Patients without the event of interest at the last follow-up or
lost to follow-up were treated as censored. (C) Representative
result of DCAF13 expression levels in normal colon and CRC cells.
(D) Relative expression levels of DCAF13 protein expression levels
in normal colon and CRC cells. **P<0.01, ***P<0.001 and
****P<0.0001. CRC, colorectal cancer; DACF13, DDB1- and
CUL4-associated factor 13; Cum, cumulative.

Figure 6

Effects of DCAF13 knockdown on
inhibiting the malignant behaviour of RKO cells. (A) Detection of
DCAF13 knockdown efficiency using quantitative reverse
transcription-quantitative PCR. (B) Detection of DCAF13 knockdown
efficiency using western blot. (C) Quantitative DCAF13 expression
levels. (D) Cell growth curve. (E) Representative PCNA expression
results. (F) Quantitative PCNA expression levels. (G)
Representative result of cell migration. Scale bar, 500 µm (H)
Quantitative result of cell migration. (I) Representative result of
cell migration by Transwell assay. Scale bar, 100 µm. (J)
Quantitative result of the cell migration assay by Transwell assay.
(K) Representative result of the clonogenicity assay. (L)
Quantitative result of clonogenicity assay. (M) Representative
result of cell adhesion. Scale bar, 100 µm. (N) Quantitative result
of the cell adhesion assay. (O) Cell cycle distribution. (P)
Percentage of cells in each cell cycle phase. (Q) Representative
expression result of EMT-related proteins. (R) Relative expression
levels of ETM-related proteins. *P<0.05, **P<0.01,
***P<0.001. CRC, colorectal cancer; DACF13, DDB1- and
CUL4-associated factor 13; PCNA, proliferating cell nuclear
antigen; sh, short hairpin; EMT, epithelial-to-mesenchymal
transition.

Figure 7

Effects of DCAF13 knockdown on
triggering transcriptome alterations of RKO cells. (A) Volcano
plots of DEGs. (B) Heat map of DEGs. (C) Biological process of GO
enrichment analysis. (D) KEGG pathway enrichment analysis. (E) TNF
signalling pathway enriched based on KEGG of GSEA. (F) Homologous
recombination enriched based on KEGG of GSEA. DACF13, DDB1- and
CUL4-associated factor 13; GO. Gene Ontology; KEGG, Kyoto
Encyclopaedia of Genes and Genomes; GSEA, Gene Set Enrichment
Analysis; FC, fold change; FDR, false discovery rate.

Figure 8

Effects of DCAF13 knockdown the
expression of homologous recombination-related proteins in RKO
cells. (A) Representative expression of homologous
recombination-related proteins. (B) Relative expression levels of
homologous recombination-related proteins. ***P<0.001. DACF13,
DDB1- and CUL4-associated factor 13.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Zhang R, Jia M, Lan S, Liu F, Jin Q, Su L and Liu G: Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer. Oncol Lett 31: 145, 2026.
APA
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q. ... Liu, G. (2026). Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer. Oncology Letters, 31, 145. https://doi.org/10.3892/ol.2026.15498
MLA
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q., Su, L., Liu, G."Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer". Oncology Letters 31.4 (2026): 145.
Chicago
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q., Su, L., Liu, G."Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer". Oncology Letters 31, no. 4 (2026): 145. https://doi.org/10.3892/ol.2026.15498
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Zhang R, Jia M, Lan S, Liu F, Jin Q, Su L and Liu G: Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer. Oncol Lett 31: 145, 2026.
APA
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q. ... Liu, G. (2026). Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer. Oncology Letters, 31, 145. https://doi.org/10.3892/ol.2026.15498
MLA
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q., Su, L., Liu, G."Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer". Oncology Letters 31.4 (2026): 145.
Chicago
Zhang, W., Zhang, R., Jia, M., Lan, S., Liu, F., Jin, Q., Su, L., Liu, G."Pro‑tumourigenic effects of DCAF13 on the progression of colorectal cancer". Oncology Letters 31, no. 4 (2026): 145. https://doi.org/10.3892/ol.2026.15498
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