Background The expression of Siglec-15, as a critical immune suppressor, in renal clear cell carcinoma (ccRCC) was few evaluated and remains unclear, especially in protein level. As previous studies reported, tumor fibrosis plays an essential role in assessing the prognosis of ccRCC, but the exact mechanism is not precise. This study evaluated the expression of Siglec-15, its role in prognosis, and the association with tumor fibrosis in ccRCC.
Methods: Immunohistochemistry was used to analyze the Siglec-15 expression in one tissue microarray (cohort A, tumor: n=134, adjacent normal tissues: n=29). Subsequently, the mRNA expression of Siglec-15 and its clinical significance in ccRCC were analyzed using The Cancer Genome Atlas database (TCGA, cohort B, n = 534) and samples. Spearman correlation coefficients were calculated for correlation analysis of correlated expression genes of Siglec-15, and then functional annotation analysis was obtained with correlated expression genes. We detected the tumor fibrosis grade in cohort C (n=32) via second harmonic generation/two-photon excitation fluorescence.
Results: Siglec-15 was overexpressed in tumor tissues compared with adjacent normal tissues in both cohort A (n=29, p<0.001) and cohort C (n=25, p<0.001). However, there was no significant difference in mRNA expression of Siglec-15 between tumor and adjacent normal tissues in cohort B (p>0.05). Moreover, over-expression of Siglec-15 is associated with higher Fuhrman grade in cohort A＆C (n=166, p=0.001, OR=3.132, 1.563-6.275), cohort B (n=534, p=0.008, OR=1.606, 1.138-2.267). Univariate Kaplan-Meir survival analysis showed that patients with high Siglec-15 mRNA expression had shorter survival periods without significance in cohort B (p=0.073). Multivariate analysis employing the Siglec-15 regression model revealed that AJCC and Fuhrman grade was the only significant independent prognostic indicators. Besides, an inverse correlation was found between Siglec-15 protein expression and the tumor's fibrosis level (p = 0.02).
Conclusions: Siglec-15 expression increases in ccRCC compared with adjacent normal tissues. Siglec-15 was frequently expressed and positively associated with pathology grade in ccRCC. This study indicated a significant role of Siglec-15 in the prognosis and immunotherapy target of ccRCC. This study also found an inverse correlation between Siglec-15 protein expression and the fibrosis level of the tumor.