The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis

Abstract

Purpose: The CA19-9 biomarker is elevated in a substantial group of patients with pancreatic ductal adenocarcinoma (PDAC), but not enough to be reliable for the detection or diagnosis of the disease. We hypothesized that a glycan called sTRA (sialylated tumor-related antigen) is a biomarker for PDAC that improves upon CA19-9. Experimental Design: We examined sTRA and CA19-9 expression and secretion in panels of cell lines, patient-derived xenografts, and primary tumors. We developed candidate biomarkers from sTRA and CA19-9 in a training set of 147 plasma samples and used the panels to make case-control calls, based on predetermined thresholds, in a 50-sample validation set and a blinded, 147-sample test set. Results: The sTRA glycan was produced and secreted by pancreatic tumors and models that did not produce and secrete CA19-9. Two biomarker panels improved upon CA19-9 in the training set, one optimized for specificity, which included CA19-9 and 2 versions of the sTRA assay, and another optimized for sensitivity, which included 2 sTRA assays. Both panels achieved statistical improvement (P < 0.001) over CA19-9 in the validation set, and the specificity-optimized panel achieved statistical improvement (P < 0.001) in the blinded set: 95% specificity and 54% sensitivity (75% accuracy), compared with 97%/30% (65% accuracy). Unblinding produced further improvements and revealed independent, complementary contributions from each marker. Conclusions: sTRA is a validated serological biomarker of PDAC that yields improved performance over CA19-9. The new panels may enable surveillance for PDAC among people with elevated risk, or improved differential diagnosis among patients with suspected pancreatic cancer.

Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma

“…But due to its low sensitivity and accuracy in clinical practice, many patients cannot be diagnosed in the early stage of cancers [6,7]. Although much progress has been made in early diagnosis, including new diagnostic markers, such as: sTAR, miR-25, etc., but the overall survival rate for PAAD has not improved in recent years [8,9]. Therefore, it is urgent to find more biomarkers as early diagnostic indicators for PAAD, guiding the treatment of the disease.…”

Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors

“…It has been shown that spatially and morphologically distinct subsets of pancreatic cancer cells expressed S-Lc 4 (here denoted sTRA) or the CA19-9 antigen (18,42). Well-differentiated ductal pancreatic adenocarcinomas typically expressed both glycans, whereas just one of the markers was expressed by poorly differentiated tumors.…”

“…More recently, sialyl-lactotetraosylceramide was also characterized in an ovarian cancer cell line (17). Additionally, S-Lc 4 has recently shown promise as a marker for pancreatic carcinomas (18), suggesting clinical applications of S-Lc 4 for epithelial tumors.…”

Predictive value of CONUT score combined with serum CA199 levels in postoperative survival of patients with pancreatic ductal adenocarcinoma: a retrospective study

“…At that time, liver, lymph nodes, peripheral vessels and nerves are often affected, with the tumor showing rapid growth, resulting in poor prognosis and the 5 year survival rate has been stagnant at 6% for decades (El-Khayat et al, 2018;Siegel, Miller & Jemal, 2019). Numerous studies have shown that tumor size, lymph node metastasis, vascular invasion and serum tumor markers (TMs) are vital prognostic factors for PC (Karamitopoulou et al, 2013;Staal et al, 2019;Winter, Yeo & Brody, 2013). Moreover, early detection of postoperative recurrence can help improve the survival rate of patients with PDAC (Wu et al, 2019); therefore, it is important to determine the factors affecting the prognosis of these patients after pancreatectomy.…”