SULF2 Expression Is a Potential Diagnostic and Prognostic Marker in Lung Cancer

Abstract

AimsLung cancer is one of the most deadly cancers; median survival from diagnosis is less than one year in those with advanced disease. Novel lung cancer biomarkers are desperately needed. In this study, we evaluated SULF2 expression by immunohistochemistry and its association with overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). We also looked for the presence of SULF2 protein in plasma to evaluate its potential as an early detection biomarker for NSCLC.MethodsWe identified patients who underwent surgical resection for pulmonary adenocarcinoma or squamous cell carcinoma at our institution. A section from each paraffin-embedded specimen was stained with a SULF2 antibody. A pathologist determined the percentage and intensity of tumor cell staining. Survival analysis was performed using a multivariate Cox proportional hazards model. Using a novel SULF2 ELISA assay, we analyzed plasma levels of SULF2 in a small cohort of healthy donors and patients with early stage NSCLC.ResultsSULF2 staining was present in 82% of the lung cancer samples. Squamous cell carcinomas had a higher mean percentage of staining than adenocarcinomas (100% vs. 60%; p<0.0005). After adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was a non-significant (31%; p = 0.65) increase in the risk of death for patients with adenocarcinoma with SULF2 staining in tumor cells. In contrast, there was a significant decrease in the risk of death (89%; p = 0.02) for patients with squamous cell carcinoma with SULF2 staining in tumor cells. SULF2 protein was present in plasma of patients with early stage NSCLC, and soluble SULF2 levels increased with age. Finally, plasma SULF2 levels were significantly elevated in early stage NSCLC patients, compared to healthy controls.ConclusionsTumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease.

Retracted: LncRNA ATB promotes proliferation and metastasis in A549 cells by down‐regulation of microRNA‐494

“…Lung cancer is a leading cause of cancer-associated death and epigenetic dysregulation of numerous signaling pathways are involved in. 31 Abnormal activation of AKT has been considered as a frequent event in lung cancer cells. 32 Likewise, the activation of the JAK/STAT3 pathway, which is required for TGF-β-induced EMT, is also frequently observed in human lung cancer.…”

TRF2 positively regulates SULF2 expression increasing VEGF-A release and activity in tumor microenvironment

“…Interestingly, by using biochemical and imaging approaches, we found that TRF2 regulates the extracellular release of VEGF-A, altering the equilibrium between cell-free and cell-associated amount of VEGF-A. This property of TRF2 is dependent on the expression of SULF2, a sulfotransferase with a potential oncogenic role that has been found overexpressed in subsets of multiple tumors (56). This enzyme, indeed, inducing post-synthetic modification of HSPGs, is capable of modulating the extracellular release of a number of growth factors containing an heparin-binding domain, including VEGF-A.…”

SULF2 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells through the ERK/AKT signaling pathway

“…Evidence from an investigation on liver cancer suggested that overexpressed SULF2 predicted a worse prognosis (25). In addition, SULF2 expression might be credited as a valuable diagnostic and prognostic biomarker in non-small cell lung cancer (26). Furthermore, Flowers et al (27) found that increased SULF2 expression was positively related to the clinical stage of head and neck squamous carcinoma.…”