ZC3H12D is a prognostic biomarker associated with immune cell infiltration in lung adenocarcinoma

Wangang Gong; Wumin Dai; Haibin Wei; Yongyi Chen; Zhiguo Zheng

doi:10.21037/tcr-20-1465

ZC3H12D is a prognostic biomarker associated with immune cell infiltration in lung adenocarcinoma

Transl Cancer Res. 2020 Oct;9(10):6128-6142. doi: 10.21037/tcr-20-1465.

Authors

Wangang Gong^{1

2

3}, Wumin Dai^{1

2

3}, Haibin Wei^{1

2

3}, Yongyi Chen^{1

2

3}, Zhiguo Zheng^{1

2

3}

Affiliations

¹ Institute of Cancer and Basic Medical (ICBM), Chinese Academy of Sciences, Hangzhou, China.
² Zhejiang Cancer Research Institute, Cancer Hospital of University of Chinese Academy of Sciences, Hangzhou, China.
³ Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, China.

Abstract

Background: ZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear.

Methods: The expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan-Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining.

Results: The combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues.

Conclusions: These findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD.

Keywords: Bioinformatics analysis; ZC3H12D; infiltration of immune cells; lung adenocarcinoma (LUAD).