J Cancer 2020; 11(20):6101-6113. doi:10.7150/jca.46902 This issue

Research Paper

Carbonic Anhydrase 4 serves as a Clinicopathological Biomarker for Outcomes and Immune Infiltration in Renal Cell Carcinoma, Lower Grade Glioma, Lung Adenocarcinoma and Uveal Melanoma

Yue Xu1,2*, Wen-Hao Xu3,5*, Shen-Nan Shi4,5*, Xiao-Long Yang1,2, Ya-Ru Ren1,2, Xin-Yu Zhuang1,2, Yuan-Yuan Qu3,5, Hai-Liang Zhang3,5✉, Xiao-Feng Zhang1,2✉

1. Department of Ophthalmology, First Affiliated Hospital of Soochow University, Suzhou, 215000, China
2. Medical College, Soochow University, Suzhou, 215000, China
3. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
4. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China
5. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20032, China
*Equal contribution

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Citation:
Xu Y, Xu WH, Shi SN, Yang XL, Ren YR, Zhuang XY, Qu YY, Zhang HL, Zhang XF. Carbonic Anhydrase 4 serves as a Clinicopathological Biomarker for Outcomes and Immune Infiltration in Renal Cell Carcinoma, Lower Grade Glioma, Lung Adenocarcinoma and Uveal Melanoma. J Cancer 2020; 11(20):6101-6113. doi:10.7150/jca.46902. Available from https://www.jcancer.org/v11p6101.htm

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Abstract

Background: Carbonic anhydrase 4 (CA4) maintains homeostasis of carbon dioxide and bicarbonate. It is suggested to be a potential prognostic biomarker, while the correlations between CA4 and different cancers are indistinct.

Methods: Differential mRNA expression of CA4 among different cancers and corresponding normal tissues was compared based on datasets on the Cancer Genome Atlas (TCGA) platforms. Then, survival analysis was performed using Tumor-immune system interactionsplatform and TCGA cohort on the basis of distinct comparison expression of CA4 in five kinds of tumors. In addition, molecular penal analysis and functional annotations of CA4-related genes was elaborated. The correlation between CA4 mRNA expression and tumor immune microenvironment were analyzed in detail.

Results: Compared with adjacent normal tissues, CA4 mRNA expressions were found significantly lower in various tumors. Moreover, decreased expression of CA4 was significantly related to worse overall survival (OS) and progression-free survival (PFS) in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), lung adenocarcinoma (LUAD) and uveal melanoma (UVM), and worse OS of prostate adenocarcinoma (PRAD) (p<0.05). Cox regression analyses indicated that CA4 was a significant prognostic biomarker in KIRC, LGG, LUAD and UVM. Moreover, CA4 showed markedly relationship with tumor immune environment and diverse immune infiltration signatures in KIRC, LGG, LUAD and UVM.

Conclusions: Our study revealed that CA4 was a potential biomarker for aggressive progression and poor prognosis in KIRC, LGG, LUAD, PRAD and UVM, correlated with immune infiltration in various tumor environments. These results suggested that CA4 possibly served as a promising prognostic and immune infiltration biomarker in many cancers.

Keywords: carbonic anhydrase 4, tumor immune microenvironment, prognosis, immune infiltration, biomarker