Background: The uncharacterized proteins of the human proteome offer an untapped potential for cancer biomarker discovery. Numerous predicted open reading frames (ORFs) are present in diverse chromosomes. The mRNA and protein expression data, as well as the mutational and variant information for these ORF proteins are available in the cancer-related bioinformatics databases.
Materials and methods: ORF proteins were mined using bioinformatics and proteomic tools to predict motifs and domains, and cancer relevance was established using cancer genome, transcriptome and proteome analysis tools.
Results: A novel testis-restricted ORF protein present in chromosome X called CXorf66 was detected in the serum, plasma and neutrophils. This gene is termed secreted glycoprotein in chromosome X (SGPX). The SGPX gene is up-regulated in cancer of the brain, lung and in leukemia, and down-regulated in liver and prostate cancer. Brain cancer in female patients exhibited elevated copy numbers of the SGPX gene.
Conclusion: The SGPX gene is a putative novel cancer biomarker. Our results demonstrate the feasibility of mining the 'dark matter' of the cancer proteome for rapid cancer biomarker discovery.
Keywords: ORF; Signal peptide; X-chromosome; biomarkers; cell trafficking; secreted protein; serum protein; uncharacterized proteins; vesicular transport; ‘dark matter’ of the genome.