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. 2023 Feb;14(1):84-93.
doi: 10.14740/wjon1571. Epub 2023 Feb 26.

The Impact of DTYMK as a Prognostic Marker in Colorectal Cancer

Abdulaziz A Aloliqi  1   2 , Abdul-Fattah Fararjeh  3   2 , Ali Al-Khader  4   5 , Ezidin Kaddumi  6 , Alaa Abdulaziz Eisa  7 , Weam Jaradat  8
Affiliations

The Impact of DTYMK as a Prognostic Marker in Colorectal Cancer

Abdulaziz A Aloliqi et al. World J Oncol. 2023 Feb.

Abstract

Background: Overexpression of deoxythymidylate kinase (DTYMK) has been associated with more aggressiveness and pathological behaviors in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC). However, the expression of DTYMK and its prognostic significance in colorectal cancer (CRC) patients are yet unknown. The goal of this study was to investigate the DTYMK immunohistochemistry reactivity in CRC tissues and to see how it correlated with various histological and clinical features as well as survival.

Methods: Several bioinformatics databases and two tissue microarrays (TMAs) of 227 cases were used in this study. Immunohistochemistry assay was used to study the protein expression of DTYMK.

Results: Based on the GEPIA, UALCAN, and Oncomine databases, DTYMK expression has increased in tumor tissues at both RNA and protein levels in colorectal adenocarcinoma (COAD) compared to normal tissues. A high DTYMK H-score was found in 122/227 (53%) of the cases, whereas a low DTYMK H-score was found in 105/227. The age at diagnosis (P = 0.036), stage of the disease (P = 0.038), and site of origin (P = 0.032) were all linked to a high DTYMK H-score. Patients with high level of DTYMK had bad overall survival. Interestingly, high DTYMK protein level was associated with PSM2 (P = 0.002) and MSH2 (P = 0.003), but not with MLH2 or MSH6.

Conclusion: This is the first study to cover the expression and prognostic significance of DTYMK in CRC. DTYMK was upregulated in CRC and could be considered as a prognostic biomarker.

Keywords: Colorectal cancer; DTYMK; H-score; Prognosis.

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Conflict of interest statement

The authors have nothing to disclose related to this work.

Figures

Figure 1
Figure 1
High expression level of DTYMK in colorectal cancer (COAD). (a) DTYMK gene expression was upregulated in several types of human malignancies especially in COAD. (b) Using GEO dataset, analysis of DTYMK expression in three pairs of tumors vs. normal of CRC patients. (c, d) Using UALCAN website, analysis of DTYMK at mRNA and protein levels. (e, f) Using Oncomine database, analysis of DTYMK in several COAD study cohorts. *P value < 0.05 was considered to be significant [16]. CRC: colorectal cancer; DTYMK: deoxythymidylate kinase; COAD: colorectal adenocarcinoma.
Figure 2
Figure 2
DTYMK protein expression by IHC. (a) These images show the DTYMK IHC grading system (original magnification × 20). Negative (0), weak (1+), moderate (2+), and strong (3+) grading systems were constructed based on DTYMK staining intensity. (b) In four cases, illustrative photographs depict examples of high DTYMK H-score and low DTYMK low H-score (original magnification was × 10 and × 20). DTYMK: deoxythymidylate kinase; IHC: immunohistochemistry.
Figure 3
Figure 3
Correlation between DTYMK and MMR proteins. (a-d) Analysis of the association between DTYMK IHC and PMS2, MLH1, MSH6 and MSH2 IHC results, respectively. P value < 0.05 was considered to be significant. (e) The overall survival (OS) and progression-free interval (PFI) analysis for high DTYMK vs. low DTYMK mRNA levels. Log rank P value < 0.05 was considered to be significant. DTYMK: deoxythymidylate kinase; IHC: immunohistochemistry; MMR: mismatch repair.
See this image and copyright information in PMC

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