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. 2019 Apr 8;11(4):497.
doi: 10.3390/cancers11040497.

Head and Body/Tail Pancreatic Carcinomas Are Not the Same Tumors

David Jérémie Birnbaum  1   2   3 , François Bertucci  4   5   6 , Pascal Finetti  7 , Daniel Birnbaum  8 , Emilie Mamessier  9
Affiliations

Head and Body/Tail Pancreatic Carcinomas Are Not the Same Tumors

David Jérémie Birnbaum et al. Cancers (Basel). .

Abstract

The association between pancreatic ductal adenocarcinoma (PDAC) location (head vs. Body/Tail (B/T)) and clinical outcome remains controversial. We collected clinicopathological and gene expression data from 249 resected PDAC samples from public data sets, and we compared data between 208 head and 41 B/T samples. The 2-year overall survival (OS) was better for the head than for the B/T PDACs (44 vs. 27%, p = 0.043), especially when comparing tumors with similar TNM classification (T3/4N0M0: 67% vs. 17%, p = 0.002) or from the same molecular class (squamous subtype: 31% vs. 0%, p < 0.0001). Bailey's molecular subtypes were differentially distributed within the two groups, with the immunogenic subtype being underrepresented in the "B/T" group (p = 0.005). Uni- and multivariate analyses indicated that PDAC anatomic location was an independent prognostic factor. Finally, the supervised analysis identified 334 genes differentially expressed. Genes upregulated in the "head" group suggested lymphocyte activation and pancreas exocrine functions. Genes upregulated in the "B/T" group were related to keratinocyte differentiation, in line with the enrichment for squamous phenotype. We identified a robust gene expression signature (GES) associated with B/T PDAC location, suggesting that head and B/T PDAC are different. This GES could serve as an indicator for differential therapeutic management based on PDAC location.

Keywords: expression profiling; pancreatic cancer; prognosis; survival; tumor location.

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Conflict of interest statement

This research was funded by Inserm/Institut Paoli-Calmettes Grant SIRIC INCa-DGOS-Inserm 6038.

Figures

Figure 1
Figure 1
Overall survival in Head or Body/Tail tumors. Kaplan–Meier overall survival (OS) curves according to PDAC location (A). All pancreatic ductal adenocarcinoma (PDAC) and (B) T1/2 N0 M0 tumors. (C) T3/4N0M0 tumors. (D) T3/4 N1 M0 tumors. T1/2N1M0 tumors have less than 10 samples in total and were not graphed). Head samples are in yellow. Body/Tail samples are in blue. The p-values (log-rank test) for the comparison between the two classes within each molecular subtype are indicated.
Figure 2
Figure 2
OS in the validation set according to Head or Body/Tail in the different Bailey’s molecular subtypes. Kaplan–Meier OS curves according to PDAC location (Head vs. B/T) and the molecular subtypes defined by Bailey (A) Squamous, (B) ADEX, and (C) Immunogenic, and (D) Pancreatic progenitor. The p-values (log-rank test) for the comparison between the two classes within each molecular subtype are indicated.
Figure 3
Figure 3
Establishment of the 334-gene expression signature between Head and B/T tumors based on the learning and validation sets. (A) Volcano plot identifying 334 genes differentially expressed (GES) between Head and B/T tumors. This volcano plot was obtained using a moderated t-test, p < 5% & q < 25%, |FC| > 2× between the Head and B/T tumors (left). The GES was used to classify the samples from the TCGA learning set (right). (B) Classification of the samples from each of the three validation sets using the 334 GES. (C) Contingency analyses of the classification in the learning and validation sets using the 334 GES identified from the learning set.
Figure 4
Figure 4
Summary of clinical, histologic, and molecular differences between head and B/T PDAC tumors.
See this image and copyright information in PMC

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