4.6 Article

Distinguishable Prognostic Signatures and Tumor Immunogenicity Between Pancreatic Head Cancer and Pancreatic Body/Tail Cancer

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.890715

Keywords

pancreatic adenocarcinoma; pancreatic head cancer; pancreatic body; tail cancers; immunologic and hallmark gene sets; prognosis

Categories

Funding

  1. National Key R&D Program of China [2019YFC1315900]
  2. Clinical Research Plan of SHDC [SHDC2020CR1035B]
  3. Innovation Group Project of Shanghai Municipal Health Commission [2019CXJQ03]
  4. National Natural Science Foundation of China [81874048]
  5. Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Municipality [21JC1404300]
  6. CSCO Clinical Oncology Research Foundation [Y-2019AZZD-0513]
  7. Shanghai Sailing Program [20YF1446400]
  8. Shanghai Key Clinical Specialty (Oncology)
  9. Shanghai Leading Talents Project
  10. Innovative Research Team of High-Level Local Universities in Shanghai [2018ZHYL0223]
  11. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161312]

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This study provides insights into the gene patterns, immune and mutational landscape characteristics, and their relationships in different locations of pancreatic adenocarcinoma (PDAC).
BackgroundPancreatic head cancer and pancreatic body/tail cancer are considered to have different clinical presentations and to have altered outcomes. MethodsNinety cases of pancreatic adenocarcinoma (PDAC) from our institution were used as a discovery set and 166 cases of PDAC from the TCGA cohort were used as a validation set. According to the anatomical location, the cases of PDAC were divided into the pancreatic head cancer group and the pancreatic body/tail cancer group. Firstly, the different biological functions of the two groups were assessed by ssGSEA. Meanwhile, ESTIMATE and CIBERSORT were conducted to estimate immune infiltration. Then, a novel anatomical site-related risk score (SRS) model was constructed by LASSO and Cox regression. Survival and time-dependent ROC analysis was used to prove the predictive ability of our model in two cohorts. Subsequently, an integrated survival decision tree and a scoring nomogram were constructed to improve prognostic stratification and predictive accuracy for individual patients. In addition, gseaGO and gseaKEGG pathway analyses were performed on genes in the key module by the R package. ResultsOverall survival and the objective response rate (ORR) of patients with pancreatic body/tail cancer were markedly superior to those with pancreatic head cancer. In addition, distinct immune characteristics and gene patterns were observed between the two groups. Then, we screened 5 biomarkers related to the prognosis of pancreatic cancer and constructed a more powerful novel SRS model to predict prognosis. ConclusionsOur research shed some light on the revelation of gene patterns, immune and mutational landscape characterizations, and their relationships in different PDAC locations.

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