Overexpression of Secreted Phosphoprotein 1 (SPP1) predicts poor survival in HPV positive cervical cancer

Abstract

Cervical cancer (CC) is the most prevalent malignant gynecological tumor with limited treatments. The present study describes the role of SPP1 in cancer progression, SPP1 emerged as one of the most overexpressed genes identified through clariom D transcriptome microarray. This investigation aims towards identifying a potential gene with significant prognostic value for detection and early diagnosis of cervical cancer. The elevated expression of SPP1 in cervical squamous cell carcinoma tissue was validated across GEO (Gene Expression Omnibus) microarray data sets, TCGA (The Cancer Genome Atlas), and Oncomine databases. SPP1 expression was found to be prognostically significant, showing association with poor survival rate of the patients. Our study intended to assess the expression of secreted phosphoprotein (SPP1) gene at mRNA and protein levels, and to explore the association of single nucleotide polymorphisms of SPP1 with risk of CC. Further, receiver operating characteristics (ROC) curve was plotted to determine the levels of SPP1 to differentiate CC against control. Results revealed significant (p < 0.01) stage-wise upregulation of SPP1 in CC compared to the normal cervical tissue and this was further confirmed using Immunohistochemistry and real-time PCR. The ROC for SPP1 demonstrated good selective power to differentiate malignant CC and non-malignant cervical tissues. The SPP1 gene −443 T > C promoter polymorphisms are found to be significantly predominant in the disease group and Insilico analysis by the TRANSFAC software confirms its association with loss of STAT6 transcription factor binding site leading to overexpression of the SPP1.