Background and Aims

Pancreatic Cancer (PC) is often discovered in late stages, which contributes to its extreme

lethality. Early detection is key to improved curative response and increased survival. This study

explored the potential of secretory mucin MUC5AC and its glycosylation (Sialyl-Lewis A and

Disialyl-Lewis A) states in combination with carbohydrate antigen CA19.9 for early diagnosis of

PC.

Methods

Sandwich ELISA and radioimmunoassay were utilized to measure patient serum for levels of

MUC5AC and CA19.9, respectively. A blinded reference set was obtained from the NCI’s Early

Detection Research Network Program (n=242): healthy control (HC, N=50), chronic pancreatitis

(CP, N=59), acute biliary obstruction (ABO, N= 30), stage IA/IB/IIA (N=52), and stage IIB PC

(N=41), to assess the diagnostic performance of MUC5AC. Further, glycans on MUC5AC

(Disialyl Lewis A, Lewis A, Blood group H (BGH) antigen) were measured via Surface

Enhanced Raman Spectroscopy (SERS).

Results

MUC5AC levels were significantly increased in patients with stage IA/IB/IIA/IIB PC in

comparison to HC, ABO and CP. MUC5AC efficiently differentiated stage IA/IB/IIA PC from

healthy controls [AUC- 0.707], ABO [AUC- 0.662], and CP [AUC- 0.745]. CA19.9

differentiated stage IA/IB/IIA PC from healthy controls [AUC- 0.727], ABO [AUC-0.537] and

CP [AUC- 0.675]. The MUC5AC combination with CA19.9 significantly improved the

performance of CA19.9 alone: healthy controls [AUC- 0.761], ABO [AUC-0 .679], and CP

[AUC- 0.753]. Further, PC serum was shown to express MUC5AC with greater Sialyl-Lewis A

glycosylation in comparison to Disialyl-Lewis A glycosylation. Further, the reverse trend for

these glycosylation was observed in CP and BC group.

Conclusions

MUC5AC is an early-stage PC biomarker that offers improved performance with CA19.9 for the

detection of PC. Also, measurement of MUC5AC glycan modification will aid in the better

differentiation of PC from healthy controls and high risk groups (CP, ABO). Further, the ratio of

disialyl to CA19.9 glycosylation of MUC5AC is a novel way to differentiate between PC and

benign conditions.

Citation Format: Chihiro Hayashi, Joseph Carmicheal, Alexey Krasnoslobodtsev, Ying Haung, Randall E. Brand,, Surinder K. Batra, Sukhwinder Kaur. Implication of secretory mucin MUC5AC and its glycan modification for detection of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-244. doi:10.1158/1538-7445.AM2017-LB-244