Combined Assessment of ERO1A Expression and CD163+ Tumor-Associated Macrophage Infiltration is Superior to Traditional Assessment Methods in Predicting Clear Cell Renal Cell Carcinoma Prognosis

Tianyu Hong¹Changjie Ren¹Hao Xiang²Yongwei Yu³Mierxiati Abudurexiti⁴Zhong Wang^4*Chao Wang^1*

• ¹Shanghai Pudong New Area Public Interest Hospital, Pudong, China
• ²Zunyi Medical University, Zunyi, China
• ³Changhai Hospital Changhai Clinical Research Center, Shanghai, China
• ⁴Shanghai Pudong New Area Gongli Hospital, Shanghai, China

Purpose: The interplay between cancer cells and tumor-infiltrating immune cells (TIICs) facilitates the development of clear cell renal cell carcinoma (ccRCC). However, it remains unclear whether the combined assessment of tumor biomarkers and TIIC density increases the accuracy of ccRCC prognosis prediction. Methods: ERO1A expression was detected in ccRCC tissue samples and cell lines. ccRCC patients from two hospitals were recruited to investigate the value of ERO1A and other TIIC biomarkers in determining ccRCC prognosis via immunohistochemistry (IHC) and statistical analyses. Results: Compared with that in the corresponding controls, ERO1A expression in ccRCC cell lines and tissues was increased and closely correlated with ccRCC progression. ERO1A expression was positively correlated with the density of infiltrating CD163+ tumor-associated macrophages (TAMs) in ccRCC. Among all groups of patients, ccRCC patients with high expression of both ERO1A and CD163 presented the highest TNM stage or Mayo Clinic stage, size, grade, and necrosis (SSIGN) score, as well as the shortest survival period. Moreover, the independent risk factors for the survival of ccRCC patients included ERO1A expression, CD163+ TAM density, TNM stage, and the SSIGN score. Time-dependent C-index analysis revealed that the combination of ERO1A expression and CD163+ TAM density was superior to either factor alone in predicting ccRCC patient survival. Furthermore, the combination of ERO1A expression and CD163+ TAM density with TNM stage or the SSIGN score had the greatest ability to predict the survival of ccRCC patients. Conclusions: Combining ERO1A expression, CD163+ TAM density, and TNM stage or SSIGN score increases the accuracy of postoperative survival prediction for ccRCC patients.