High S100A8 and S100A12 protein expression is a favorable prognostic factor for survival of oropharyngeal squamous cell carcinoma

Abstract

S100/calgranulins (S100A8, S100A9 and S100A12) are key players of innate immune function and elevated levels are a characteristic feature of acute and chronic inflammation, and inflammation-associated carcinogenesis. However, reduced S100A8 and S100A9 expression has been detected for squamous cell carcinoma, including the head and neck region (HNSCC), which originate from mucosal epithelia with abundant expression of both proteins under physiological conditions. In contrast to S100A8 and S100A9, only sparse information is available for S100A12 and a comparative study of all three S100/calgranulins in HNSCC is still missing. We analyzed S100/calgranulin protein levels in a retrospective patient cohort (n 5 131) of oropharyngeal squamous cell carcinoma (OPSCC) by immunohistochemical staining of tissue microarrays. Common characteristics of all three S100/calgranulins were: (i) abundant expression in supra-basal keratinocytes of normal mucosa with predominant nuclear staining, (ii) low expression in 30.4-51.9% of primary OPSCCs and (iii) variable accumulation of S100/calgranulin-positive immune cells in the tumor stroma. These features were associated with histopathological characteristics, such as tumor grade, lymph node metastasis and tumor stage. Furthermore, univariate and multivariate analysis revealed worse overall survival of OPSCC patients with simultaneous reduction of S100A8 and S100A12 expression, while expression of S100A9 or presence of the S100A8/S100A9 heterodimer had no impact, suggesting distinct regulation and function of individual S100/ calgranulins in the pathogenesis of HNSCCs.Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent human malignancies worldwide characterized by high mortality and high morbidity.

Downregulation of S100 Calcium Binding Protein A12 inhibits the growth of glioma cells

“…The present study was in line with the earlier study on the expression of S100A12, which was highly correlated with the prognosis and high survival rates of oropharyngeal squamous cell carcinoma patients 10 . Huang et al has also demonstrated that S100A12 might be serve as a new prognostic target to examine the recurrence and progression of the early stage of hepatectomy 17 .…”

“…It has been reported that high levels of S100A12 has been correlated with good prognosis for patients with oropharyngeal squamous cell carcinoma 10 . In addition, S100A12 was significantly increased in colorectal cancer samples when compared adjacent normal colon tissues 11 .…”

S100A8+stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma

“…Tumor microenvironment plays critical roles in tumor cells malignance and patients survival. 27,28 Given the existing significance of tumor microenvironment, we sought to create a new scoring system, the SATB index, to better predict tumor progression and survival. In addition to the TB grade, which is a well-documented predictor of survival, [19][20][21] the Kaplan-Meier analysis indicated that the S100A8 C TIF was a protective factor for survival.…”

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis

“…Although no significant association was observed between the overall survival rate of patients with breast cancer and the expression of this protein (P=0.094), positive S100-A8 expression was revealed to potentially contribute to a longer overall survival time for patients with breast cancer. This protein has also been reported to be a survival-associated factor in oropharyngeal squamous cell carcinoma (34). However, protein S100-A8 was also demonstrated to be a marker of poor prognosis for invasive ductal carcinoma of the breast (35).…”