Abstract
PurposeHypodensity of pancreatic ductal adenocarcinoma (PDAC) during contrast-enhanced computed tomography (CECT) examination is common, but a minority of PDAC patients exhibit hyperdense images. The present study examined the clinical characteristics and protein landscape of PDAC with hyperdensity.Materials and MethodsA total of 844 pathologically confirmed PDAC patients who underwent CECT before surgery were included. During the parenchymal phase of CECT, patients were assigned to the hyperdense or hypodense group based on CT values. Clinical and CT characteristics for predicting relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards model. The expression of the tumor angiogenesis marker CD31 and stroma-related protein CTHRC1 were analyzed using immunohistochemistry (IHC) assay to evaluate differences between the two groups. Proteomics was performed to compare the possible mechanisms underlying the differential enhancement on CT scans.ResultsBased on CECT, 43 and 801 PDAC patients had hyperdense and hypodense lesions, respectively. All 43 patients presented a hyperdense lesion in the parenchymal phase. The mean CECT values of the hyperdense group were higher than the hypodense group (102.5 ± 17.4 and 53.7 ± 18.7, respectively, P < 0.001). The hyperdense group had a better prognosis than the hypodense group (median RFS, 19.97 vs. 12.34 months, P = 0.0176; median OS, 33.6 vs. 20.3 months, P = 0.047). Multivariate analysis showed that age, higher CA19-9 levels (> 300 U/ml), tumor stage, tumor differentiation, tumor CT density, and adjuvant chemotherapy were significant independent prognostic factors for OS. CD31 immunohistochemical staining showed that the hyperdense PDACs had a higher microvessel density than the hypodense group (P < 0.001). CTHRC1 expression was higher in the hypodense group (P = 0.019). Sixty-eight differentially expressed proteins were found using the tandem mass tag labeling-based quantification of the proteomes of PDAC tissue samples, and 7 proteins (POFUT1, PKP2, P0DOX4, ITPR1, HBG2, IGLC3, SAA2) were related to angiogenesis.ConclusionPatients who presented with a hyperdense mass on CECT had a higher microvessel density and better prognosis. Anti-angiogenic therapy may be suitable for these patients.
Highlights
Pancreatic cancer is a lethal disease with a dismal prognosis, and its mortality rate is almost equal to its morbidity rate [1]
The tumor border and growth pattern data were not collected because this study mainly focused on the mass density in radiology
A total of 844 patients (498 males, 59.0%; 346 females, 41.0%) with surgically and pathologically confirmed pancreatic adenocarcinoma (PDAC) were enrolled in this study
Summary
Pancreatic cancer is a lethal disease with a dismal prognosis, and its mortality rate is almost equal to its morbidity rate [1]. The 5year survival remains at 5%–8%, and it is expected to become the second leading cause of cancer-related death in 2030 [1, 2]. Surgical resection is the only curative treatment, but less than 20% of patients are candidates for surgery at the time of diagnosis, and less than 20% of these patients survive 5 years after surgery [1]. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology have recommended MDCT for the prediction of resectability and potential for reconstruction [3]. Imaging examination plays a significant role in the treatment of patients with pancreatic adenocarcinoma (PDAC) [4]. The precision of the diagnosis and prediction of resectability is more than 85% [6]
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