DTYMK Expression Predicts Prognosis and Chemotherapeutic Response and Correlates with Immune Infiltration in Hepatocellular Carcinoma

Yiwen Guo; Weixin Luo; Shanzhou Huang; Wenting Zhao; Huadi Chen; Yihao Ma; Maodong Ye; Yu Nie; Yixi Zhang; Changjun Huang; Qi Zhou; Xiaoshun He; Maogen Chen

doi:10.2147/JHC.S312604

DTYMK Expression Predicts Prognosis and Chemotherapeutic Response and Correlates with Immune Infiltration in Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2021 Aug 3:8:871-885. doi: 10.2147/JHC.S312604. eCollection 2021.

Authors

Yiwen Guo^#^{1

2

3}, Weixin Luo^#^{1

2

3}, Shanzhou Huang^#⁴, Wenting Zhao⁵, Huadi Chen^{1

2

3}, Yihao Ma^{1

2

3}, Maodong Ye^{1

2

3}, Yu Nie^{1

2

3}, Yixi Zhang⁶, Changjun Huang^{1

2

3}, Qi Zhou^{7

8}, Xiaoshun He^{1

2

3}, Maogen Chen^{1

2

3}

Affiliations

¹ Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
² Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, People's Republic of China.
³ Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, People's Republic of China.
⁴ Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
⁵ School of Traditional Chinese Medicine, Southern Medical University, Guangdong, Guangzhou, 510515, People's Republic of China.
⁶ Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100005, People's Republic of China.
⁷ Department of General Surgery, Hui Ya Hospital of The First Affiliated Hospital, Sun Yat-sen University, Huizhou, Guangdong, 516081, People's Republic of China.
⁸ Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified.

Methods: Samples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment.

Results: We found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis.

Discussion: We found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.

Keywords: DTYMK; TCGA; cell cycle; hepatocellular carcinoma; immune infiltration.