Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study

Abstract

Background: To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection.

Methods: This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital.

Results: The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3-9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7-61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6-66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8-54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68-11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85-8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17-3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973).

Conclusion: Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.

Keywords: ATG12; duodenal adenocarcinoma; histopathological phenotype; lymph node metastases; overall survival.

Figure 1

Kaplan−Meier survival curves comparing the overall survival of patients after resection of duodenal adenocarcinomas grouped by tumor anatomical location of origin.

Figure 2

Immunohistochemical staining of duodenal carcinomas tissue. (A) Immunohistochemical stains of intestinal type: positive for CDX2 (left), CK20 (middle), and MUC2 (right) markers. (B) Immunohistochemical stains of gastric type: positive for MUC5AC (middle) and MUC6 (right) markers. (C) Immunohistochemical stains of pancreatic type: positive for MUC1 (middle) and CK7 (right) markers.

Figure 3

(A) Kaplan−Meier survival curves comparing the overall survival of patients after resection of duodenal adenocarcinomas grouped by histopathological phenotype. (B–D) Kaplan−Meier survival curves comparing the overall survival of patients after resection of duodenal adenocarcinomas grouped by histopathological phenotype between the three tumor anatomical locations of origin.

Figure 4

Identification of differentially expressed genes (DEGs) in duodenal adenocarcinomas. DEGs in duodenal adenocarcinoma for the group of gastric type vs. intestinal type, gastric type vs. pancreatic type, and pancreatic type vs. intestinal type. (A) Volcano plot. (B) Bar histogram. (C) Venn diagram.

Figure 5

Cluster analysis of differentially expressed proteins in the group of gastric type, pancreatic type, and intestinal type. The hierarchical clustering results are represented as a tree heat map, with the ordinate representing significantly differentially expressed proteins and the abscissa representing sample information. Significant differences in protein expression in the different numerical expression quantities (log₂ expression) of the samples with different colors are shown on the heat map, where red or blue represents significantly upregulated or downregulated proteins, and gray represents no quantitative information for proteins. ATG12 represents the protein name of Q94817, IGF2 represents the protein name of p03814, and IRS2 represents the protein name of Q9Y4H2.

Figure 6

Gene ontology functional enrichment analysis of gastric vs. intestinal, gastric vs. pancreatic, and pancreatic vs. intestinal differentially expressed proteins. (A–C) Represent biological processes analysis, cellular components analysis, and molecular function analysis. (D–F) The number of differentially expressed proteins enriched in each entry.

Figure 7

Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of gastric vs. intestinal (A), gastric vs. pancreatic (B), and pancreatic vs. intestinal (C), differentially expressed protein signaling pathways. IRS2, IGF2, and ATG12 proteins are present mainly in cancer metabolic pathways (containing MAPK, FoxO, and RAS signaling pathways).

Figure 8

Differentially expressed protein interaction networks in the group of gastric type vs. intestinal type (A), gastric type vs. pancreatic type (B), and pancreatic type vs. intestinal type (C). (D) ATG12, IGF2, and IRS2 involved interacting proteins.

Figure 9

Immunohistochemical staining of duodenal carcinoma tissue stained with (A) ATG12, (B) IRS2, and (C) IGF2 antibodies. For all antibodies, proteins are detected in both the cytoplasm and the nuclei of tumor cells.

Figure 10

Kaplan−Meier survival curves of the overall survival of patients with duodenal adenocarcinoma with high expression of ATG12 (A), IRS2 (B), and IGF2 (C) compared with those patients with low expression of ATG12, IRS2, and IGF2.