High-Level S100A6 Promotes Metastasis and Predicts the Outcome of T1–T2 Stage in Clear Cell Renal Cell Carcinoma

Abstract

S100A6 (calcyclin), functions in cell cycle progression and differentiation, has been reported to promote the tumorigenesis and malignancy of many types of cancers. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, lacking both promising prognostic markers and effective therapeutic targets. In our previous study, we have found the elevated S100A6 in the ccRCC tumor tissues, and the differentially expressed genes determined by microarray analysis were found to be strongly related to tumor metastasis after S100A6 knockdown and overexpression in the ccRCC cell line 786-O. The mRNA expression of S100A6 detected by RT-PCR in 6 cell lines and 174 tumor tissues, including 58 metastatic ccRCC and 116 clinicopathological features paired non-metastatic ccRCC (1:2), indicated S100A6 was elevated in the metastatic cells and tumor tissues. The protein expression was consistent with mRNA expression. The biological function of S100A6 in promoting metastasis was determined through overexpression and knockdown of S100A6 in the ccRCC cell lines 786-O, caki-1, and ACHN. In the scratch wound migration assay as well as migration and invasion assays, S100A6 knockdown significantly suppressed the migratory and invasive abilities of tumor cells, whereas overexpression enhanced the malignancy. Further research with the follow-up data of 129 ccRCC patients were analyzed by the Cox regression and survival analysis. The expression of S100A6 was up-regulated in metastatic ccRCC cells. In the metastatic tumor tissues, the expression of S100A6 was also higher than in the non-metastatic tissues. High S100A6 expression might be crucial to promote metastasis in ccRCC by enhancing the ability of tumor cells migration and invasion. In addition, the quantitative mRNA expression of S100A6 in the tumor tissues was an independent risk factor and might be used as a prognostic marker for the metastatic risk of the localized T1-T2 stage ccRCC.

Serum levels of S100A6 are unaltered in patients with resectable cholangiocarcinoma

“…Similar observations were made for S100A2 as a negative prognostic biomarker in pancreatic cancer [53]. In line, S100 family members, including S100A6, have been demonstrated to regulate critical processes such as tumor growth, metastasis, angiogenesis and immune evasion [54–57].…”

Distinct prognostic values of S100 mRNA expression in breast cancer

“…Increased expression of S100A6 has been reported to be related to the progression and invasive process of several human carcinomas4243444546. Elevated expression of S100A6 protein is an independent prognostic marker in gastric cancer and pancreatic cancer patients4344.…”

Changes in Serum and Salivary Proteins in Canine Mammary Tumors

“…Higher tissue expression of S100A2 was significantly correlated with worse overall survival in ovarian cancer patients [15], and S100A2 protein expression in saliva was observed to be higher in oral squamous cell carcinoma patients in comparison to other oral potentially malignant disorders. S100A6 expression has been associated with worse prognosis or the progression of several cancers including oncogynecology [50], colorectal [51], gastric [52], and renal [53]. In contrast, a recent study suggests a relation between S100A6 expression and better prognosis in breast cancer [54].…”