A novel secretin receptor splice variant potentially useful for early diagnosis of pancreatic carcinoma

Hayes, Gregory M; Carrigan, Patricia E; Dong, Maoqing; Reubi, Jean Claude; Miller, Laurence J (2007). A novel secretin receptor splice variant potentially useful for early diagnosis of pancreatic carcinoma. Gastroenterology, 133(3), pp. 853-61. Philadelphia, Pa.: Elsevier 10.1053/j.gastro.2007.06.013

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BACKGROUND ; AIMS: Pancreatic and bile duct carcinomas represent highly aggressive malignancies that evolve from secretin receptor-rich ductular cells. With premessenger RNA splicing abnormalities common in cancer, we evaluated whether an abnormal secretin receptor spliceoform were present, characterized it, and developed a serum assay for it. METHODS: Cancer cell lines and healthy and neoplastic tissue were studied by nested reverse-transcription polymerase chain reaction and sequencing. A promising spliceoform was isolated and characterized, and monoclonal antibodies were raised to 2 distinct regions. A dual antibody enzyme-linked immunosorbent assay was developed and applied to blinded serum samples from 26 patients with pancreatic carcinoma, 10 patients with chronic pancreatitis, and 14 controls. RESULTS: Each of 9 pancreatic cancer specimens and no normal tissue expressed a secretin receptor variant with exons 3 and 4 deleted. This encoded a 111-residue peptide with its first 43 residues identical to wild-type receptor, but, subsequent to a shift in coding frame and early truncation, the next 68 residues were unique in the transcriptome/proteome. This nonfunctional soluble protein did not bind or signal in response to secretin and was secreted from transfected MiaPaCa-2 cells. Elevated serum levels of this variant were present in 69% of pancreatic cancer patients, 60% of chronic pancreatitis patients, and 1 of 14 controls. CONCLUSIONS: We identified a novel abnormal spliceoform of the secretin receptor in pancreatic and bile duct cancers and developed a dual antibody sandwich enzyme-linked immunosorbent assay to measure it in the circulation. Initial application of this assay in patients with pancreatic cancer and chronic pancreatitis was promising, but additional validation will be required to evaluate its clinical utility.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Reubi-Kattenbusch, Jean-Claude
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	0016-5085
ISBN:	17678920
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:54
Last Modified:	05 Dec 2022 14:16
Publisher DOI:	10.1053/j.gastro.2007.06.013
PubMed ID:	17678920
Web of Science ID:	000249326900019
URI:	https://boris.unibe.ch/id/eprint/22743 (FactScience: 36402)