Qualitative diagnostic signature for pancreatic ductal adenocarcinoma based on the within-sample relative expression orderings

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancer, which is one of the most aggressive malignant neoplasms with a 9.3% five-year survival rate. The pathological biopsy is the current golden standard for confirming suspicious lesions of PDAC, but it is not entirely reliable because of the insufficient sampling amount and inaccurate sampling location. Therefore, developing a robust signature to aid the accurate diagnosis of PDAC is critical.

Methods: Based on the within-sample relative expression orderings of gene pairs, we identified a qualitative signature to discriminate both PDAC and adjacent samples from both chronic pancreatitis and normal samples in the training datasets and validated it in other independent datasets produced by different laboratories with different measuring platforms.

Results: A six-gene-pair signature was identified in the training data and validated in eight independent datasets. For surgical samples, 96.63% of 356 PDAC tissues, 100% of 11 pancreatitis tissues of non-cancer patients, and 23 of 24 normal pancreatic tissues were correctly classified. Especially, 59 of 60 cancer-adjacent normal tissues of PDAC patients were correctly identified as PDAC. For biopsy samples, all of 11 PDAC biopsy tissues were correctly classified as PDAC.

Conclusion: The signature can distinguish both PDAC and PDAC-adjacent normal tissues from both chronic pancreatitis and normal tissues of non-cancer patients even when the sampling locations are inaccurate, which can aid the diagnosis of PDAC.

Keywords: Diagnostic signature; Pancreatic ductal adenocarcinoma; Pancreatitis; Relative expression orderings.