High expression of SEZ6L2 as an independent prognostic Indicator in thyroid carcinoma

Abstract

Background: Seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) is a type 1 transmembrane protein that is primarily expressed in the brain. In recent reports, SEZ6L2 has been found to be overexpressed in some cancers and can drive the progression of tumors. However, its function and mechanism in thyroid cancer remain unclear. Methods: In this article,we searched for the SEZ6L2 expressions in Pan-cancer on TCGA (The Cancer Genome Atlas) and evaluated these data using the TIMER2 method. Then, the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was collected in human protein mapping (HPA) data. And we used CIBERSORT to assess the association between the levels of SEZ6L2 expression and the number of various immune cells in papillary thyroid carcinoma (PTC) tissue. Finally, Gene Expression Omnibus (GEO) analyses, real-time quantitative polymerase chain reaction (qRT-PCR) of tissues, and immunohistochemical staining were used to detect the result. Results: The article illustrated that a large number of cancers had a higher expression of SEZ6L2 compared to the control tissues. And the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was considerably elevated compared to that in normal tissues SEZ6L2 was elevated in thyroid carcinoma (THCA) tissue, besides, GEO analyses, qRT-PCR of tissues, and immunohistochemical staining were conducted to test the results. Finally, the Kaplan-Meier survival analysis illustrated that the increased expression of SEZ6L2 was correlated with a dismal prognosis-higher SEZ6L2 is associated with shorter survival. And the univariate analysis illustrated that T stage, SEZ6L2 and Pathologic stage were related to the overall survival (OS), multivariate analysis stated that elevated expression of SEZ6L2 was an independent risk factor that affected progression-free interval (PFI) (P<0.05). Consequently, we found that the expression of SEZ6L2 was correlated with tumor-infiltrating immune cells by TIMER. Conclusions: SEZ6L2 was upregulated in patients with THCA and that increased expression of SEZ6L2 was related with clinical progression and was regarded as an independent risk factor for PFI. In THCA patients, the expression of SEZ6L2 could be a significant prognostic factor, which is expected to be a prospective biomarker for THCA in the future.