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. 2024 Jan 11:14:1289548.
doi: 10.3389/fimmu.2023.1289548. eCollection 2023.

DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma

Zhibo Zhang #  1 , Mingxiu Ju #  1 , Zhongming Tang  1 , Zhen He  1 , Shengni Hua  1
Affiliations

DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma

Zhibo Zhang et al. Front Immunol. .

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for ~90% of the total cases. DnaJ heat shock protein family member C8 (DNAJC8), belonging to the heat shock protein 40 (HSP40) family, is known to regulate cancer biology function. However, the role of DNAJC8 on HCC development remains unknown.

Methods: The Cancer Genome Atlas, GTEx, cBioPortal, and Human Protein Atlas were used to analyze the expression and clinical significance of DNAJC8 in HCC. Two HCC cell lines, MHCC-97H and Huh-7, were utilized to determine the biological function of DNAJC8.

Results: DNAJC8 expression was upregulated in HCC tissues and correlated with poor clinical prognosis. It was closely related to spliceosome, nucleocytoplasmic transport, and cell cycle and might be involved in the formation of tumor immunosuppressive microenvironment. Knockdown of DNAJC8 severely inhibited HCC cell proliferation and induced apoptosis.

Conclusion: Our study demonstrate that DNAJC8 functions as an oncogene in HCC and hence may be used as a potential therapeutic target and prognostic marker for HCC.

Keywords: DNAJC8; apoptosis; bioinformatics analysis; hepatocellular carcinoma; tumor immune microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
DNAJC8 expression is upregulated in HCC. (A) mRNA expression of DNAJC8 in paired samples from TCGA. (B) Protein expression of DNAJC8 between normal and tumor tissue from UALCAN. (C) Expression difference of DNAJC8 in Human Protein Atlas database. (D) The respective relationship between DNAJC8 expression and methylation (left), copy number (right). (E) Relationship between gene mutation and DNAJC8 expression (left: high; right: low). ***: p<0.001.
Figure 2
Figure 2
DNAJC8 expression is closely associated with HCC prognosis. (A) Survival analysis of DNAJC8 expression (left: overall survival; middle: progression-free survival; right: disease-specific survival) in TCGA. (B) The ROC curve of DNAJC8. (C) Survival analysis of DNAJC8 expression in GEPIA. (D) Relationship between DNAJC8 expression and clinical characteristics. (E) Logistics regression analysis between DNAJC8 and clinical characteristics. *: p<0.05; **: p<0.01.
Figure 3
Figure 3
Enrichment analysis of DNAJC8-related genes. (A) The heat map of DNAJC8-related genes (left: positive correlation; right: negative correlation). (B) GO and KEGG analysis about DNAJC8-related genes. (C) GSVA analysis of DNAJC8-related genes. (D) PPI analysis of DNAJC8.
Figure 4
Figure 4
Abnormal expression of DNAJC8 affects tumor immune microenvironment. (A) Immune infiltration analysis using GSE datasets. (B) Immune infiltration analysis using TCGA datasets. (C) Relationship between DNAJC8 and immune checkpoints.
Figure 5
Figure 5
DNAJC8 expression in patients and cell lines. (A) Expression of DNAJC8 in paired samples from HCC patients. (B) Expression of DNAJC8 in HCC cell lines. (C) Immunohistochemical staining of HCC patient tissues (n=11). *: p<0.05; **: p<0.01; ***: p<0.001.
Figure 6
Figure 6
DNAJC8 knockdown inhibits HCC cell proliferation and induces apoptosis. (A) Growth curve of Huh-7 and MHCC-97H. (B) Colony formation assay of Huh-7 and MHCC-97H. (C) EDU assay of Huh-7 and MHCC-97H. (D) Apoptosis analysis of Huh-7 and MHCC-97H. (E) The up-regulation of Bax caused by the knock down of DNAJC8. *: p<0.05; **: p<0.01; ***: p<0.001.
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