Glycobiomarker, Fucosylated Short-Form Secretogranin III Levels Are Increased in Serum of Patients with Small Cell Lung Carcinoma

Abstract

Secretogranin III (SgIII) is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Granins are expressed in endocrine and neuroendocrine cells and subsequently processed into bioactive hormones. Although granin-derived peptide expression is correlated with neuroendocrine carcinomas, little is known about SgIII. We previously identified SgIII by a comparative glycoproteomics approach for elucidation of glycobiomarker candidates in lung carcinoma. Here, we examined the expression, secretion, and glycosylation of SgIII to identify novel biomarkers of small cell lung carcinoma (SCLC). In comparative immunohistochemical analysis and secretion profiling, SgIII was observed in all types of lung cancer. However, low-molecular-weight SgIII (short-form SgIII) was specifically found in SCLC culture medium. Glycoproteomics analysis showed that a fucosylated glycan was attached to the first of three potential N-glycosylation sites and an unfucosylated glycan was detected on the second site; however, the third site was not glycosylated. Next, we performed lectin capture with a fucose-binding lectin and detected short-form SgIII specifically in the sera of patients with SCLC. The results suggested an association between the fucosylated glycoform of short-form SgIII and SCLC. Thus, fucosylated short-form SgIII may be a valuable biomarker for SCLC and could be used to monitor development of the disease. All MS data are available via ProteomeXchange and jPOST with identifiers PXD007626 and JPST000313, respectively.

lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis

“…Also, the upregulation of SLC39A14 in tumor cells may be attributed to the loss of its interactive gene p53, a tumor suppressor (Zhao et al, 2017). Although there were no studies to discuss the roles of SCG5 in cancer, its family members secretogranin II and III have been seen to be overexpressed in prostate cancer (Courel et al, 2014) and small cell lung carcinoma (Togayachi et al, 2017), suggesting SCG5 may also be oncogenic for LSCC. Zinc finger proteins had also been observed to promote cell growth and metastasis in nasopharyngeal carcinoma (Li et al, 2015).…”

Identification of Poly-N-Acetyllactosamine-Carrying Glycoproteins from HL-60 Human Promyelocytic Leukemia Cells Using a Site-Specific Glycome Analysis Method, Glyco-RIDGE

“…We therefore developed a method for large-scale identification of glycopeptides (peptide sequences and glycosylated sites) by glycopeptide capture, PNGase-mediated removal of glycans, and liquid chromatography (LC)/mass spectrometry (MS) analysis [ 7 , 8 ]. This approach has facilitated the discovery of glycobiomarker candidates in hepatocellular carcinoma, lung adenocarcinoma, small cell lung carcinoma, and ovarian clear cell carcinoma [ 9 – 14 ] and has enabled the identification of glycosylated proteins from various organisms, including Caenorhabditis elegans , mice, and humans [ 15 – 19 ]. This knowledge was then used to construct a glycoprotein database, GlycoProtDB [ 16 ].…”

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules

“…Once we have found and validated one or more lectin probes with biological significance, they can be easily used as potential disease biomarkers in routine tests for a large number of clinical specimens by lectin-antibody ELISA. Currently, this approach has proved useful in screening novel biomarkers for disease diagnosis, including lung cancer [27].…”