Abstract
Clinical data mining and bioinformatics analysis can be employed effectively to elucidate the function and underlying mechanisms of the gene of interest. Here, we have proposed a framework for the identification and validation of independent biomarkers in human cancer and for mechanistic profiling using gene sets enrichment analysis and pathway analysis. This is followed by validation with in vitro experiments. Using this framework to analyze the clinical relevance of SEC23A, we have discovered the prognostic potential of SEC23A in different cancers and identified SEC23A as an independent prognostic factor for poor prognosis in bladder cancer, which implicates SEC23A, for the first time, as an oncogene. Bioinformatic analyses have elucidated an association between SEC23A expression and the upregulation of the MAPK signaling pathway. Using the T24 human bladder cell line, we confirmed that knockdown of SEC23A expression could effectively impact the MAPK signaling pathway. Further, through PCR verification, we showed that MEF2A, one of the key genes of the MAPK signaling pathway, might be a downstream factor of the SEC23A gene.
Highlights
Tumor metastasis is responsible for the majority of cancer-associated mortalities (Gupta and Massagué, 2006)
We have proposed a framework for the identification and validation of independent biomarkers in human cancer and for mechanistic profiling using gene sets enrichment analysis and pathway analysis. This is followed by validation with in vitro experiments. Using this framework to analyze the clinical relevance of SEC23A, we have discovered the prognostic potential of SEC23A in different cancers and identified SEC23A as an independent prognostic factor for poor prognosis in bladder cancer, which implicates SEC23A, for the first time, as an oncogene
We report that SEC23A mRNA expression is associated with the overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in some cancers such as adrenocortical carcinoma, bladder urothelial carcinoma (BLCA), cervical cancer, kidney renal papillary cell carcinoma, and uveal melanoma
Summary
Tumor metastasis is responsible for the majority of cancer-associated mortalities (Gupta and Massagué, 2006). Despite the improvements in cancer diagnosis and treatments, the lack of effective predictive molecular markers for monitoring disease progression and prediction of the outcome of treatment has resulted in unsatisfactory clinical outcomes for most cancers. The identification of new independent molecular markers that can provide a more accurate prognosis is key to the outcome of individualized treatment therapy for tumors. Previous studies have revealed involvement of SEC23A in Cranio-lenticulosutural dysplasia, an autosomal recessive disease with defects in collagen secretion, which leads to craniofacial and skeletal malformations (Boyadjiev et al, 2006, 2011). Few published studies by others have shown an inhibitory role of SEC23A in human cancer progression its expression
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