PMID- 37026827
OWN - NLM
STAT- MEDLINE
DCOM- 20240222
LR  - 20240222
IS  - 1743-9159 (Electronic)
IS  - 1743-9191 (Print)
IS  - 1743-9159 (Linking)
VI  - 109
IP  - 7
DP  - 2023 Jul 1
TI  - Specific human leukocyte antigen class I genotypes predict prognosis in resected 
      pancreatic adenocarcinoma: a retrospective cohort study.
PG  - 1941-1952
LID - 10.1097/JS9.0000000000000264 [doi]
AB  - BACKGROUND: Patients with resected pancreatic adenocarcinoma (PAAD) often 
      experience short-term relapse and dismal survival, suggesting an urgent need to 
      develop predictive and/or prognostic biomarkers for these populations. Given the 
      potential associations of the human leukocyte antigen class I ( HLA -I) genotype 
      with oncogenic mutational profile and immunotherapy efficacy, we aimed to assess 
      whether differential HLA -I genotype could predict the postoperative outcomes in 
      resected PAAD patients. MATERIALS AND METHODS: HLA -I ( A , B , and C ) 
      genotyping and somatic variants of 608 Chinese PAAD patients were determined by 
      targeted next-generation sequencing of matched blood cells and tumor tissues. HLA 
      - A / B alleles were classified with the available definition of 12 supertypes. 
      The Kaplan-Meier curves of disease-free survival (DFS) and multivariable Cox 
      proportional-hazards regression analyses were performed to determine the survival 
      difference in 226 selected patients with radical resection. Early-stage (I-II) 
      patients constituted the majority (82%, 185/226) and some stage I-II individuals 
      with high-quality tumor samples were analyzed by RNA-sequencing to examine 
      immunophenotypes. RESULTS: Patients with HLA-A02 + B62 + B44 - had significantly 
      shorter DFS (median, 239 vs. 410 days; hazard ratio=1.65, P =0.0189) than 
      patients without this genotype. Notably, stage I-II patients carrying HLA-A02 + 
      B62 + B44 - had sharply shorter DFS than those without HLA-A02 + B62 + B44 - 
      (median, 237 vs. 427 days; hazard ratio=1.85, P =0.007). Multivariate analysis 
      revealed that HLA-A02 + B62 + B44 - was associated with significantly inferior 
      DFS ( P =0.014) in stage I-II patients but not in stage III patients. 
      Mechanistically, HLA-A02 + B62 + B44 - patients were associated with a high rate 
      of KRAS G12D and TP53 mutations, lower HLA-A expression, and less inflamed T-cell 
      infiltration. CONCLUSION: The current results suggest that a specific combination 
      of germline HLA-A02/B62/B44 supertype, HLA-A02 + B62 + B44 - , was a potential 
      predictor for DFS in early-stage PAAD patients after surgery.
CI  - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Wen, Chenlei
AU  - Wen C
AUID- ORCID: 0000-0003-3458-5409
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Zhang, Lei
AU  - Zhang L
AUID- ORCID: 0000-0002-2428-9772
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Yang, Ying
AU  - Yang Y
AUID- ORCID: 0000-0002-0026-7659
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Jin, Yangbing
AU  - Jin Y
AUID- ORCID: 0000-0003-1330-0531
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Ren, Dandan
AU  - Ren D
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Zhang, Zehui
AU  - Zhang Z
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Zou, Siyi
AU  - Zou S
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Li, Fanlu
AU  - Li F
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Sun, Huaibo
AU  - Sun H
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Jin, Jiabin
AU  - Jin J
AUID- ORCID: 0000-0003-0902-7544
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Lu, Xiongxiong
AU  - Lu X
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Xie, Junjie
AU  - Xie J
AUID- ORCID: 0000-0002-9732-1841
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Cheng, Dongfeng
AU  - Cheng D
AUID- ORCID: 0000-0001-8648-1631
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Xu, Zhiwei
AU  - Xu Z
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Chen, Huan
AU  - Chen H
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Mao, Beibei
AU  - Mao B
AD  - Genecast Biotechnology Co. Ltd, Wuxi, Jiangsu Province.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Wang, Jiancheng
AU  - Wang J
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Deng, Xiaxing
AU  - Deng X
AUID- ORCID: 0000-0002-0762-4110
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Peng, Chenghong
AU  - Peng C
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Li, Hongwei
AU  - Li H
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Jiang, Cen
AU  - Jiang C
AD  - Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine.
FAU - Lin, Lin
AU  - Lin L
AUID- ORCID: 0000-0003-1150-9438
AD  - Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine.
FAU - Zhang, Henghui
AU  - Zhang H
AD  - Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical 
      University, Beijing, China.
AD  - Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing Shijitan 
      Hospital, Capital Medical University, Beijing, China.
FAU - Chen, Hao
AU  - Chen H
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Shen, Baiyong
AU  - Shen B
AUID- ORCID: 0000-0002-3994-248
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
FAU - Zhan, Qian
AU  - Zhan Q
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of 
      Medicine.
AD  - State Key Laboratory of Oncogenes and Related Genes, National Research Center for 
      Translational Medicine (Shanghai), Shanghai.
LA  - eng
SI  - ClinicalTrials.gov/NCT05483257
PT  - Journal Article
DEP - 20230701
PL  - United States
TA  - Int J Surg
JT  - International journal of surgery (London, England)
JID - 101228232
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - *Pancreatic Neoplasms/diagnosis/genetics/surgery
MH  - *Adenocarcinoma/diagnosis/genetics/surgery
MH  - Genotype
MH  - Retrospective Studies
MH  - HLA Antigens
MH  - East Asian People
PMC - PMC10389500
COIS- The authors declare that they have no financial conflict of interest with regard 
      to the content of this report. Sponsorships or competing interests that may be 
      relevant to content are disclosed at the end of this article.
EDAT- 2023/04/08 06:00
MHDA- 2023/07/25 06:43
PMCR- 2023/07/31
CRDT- 2023/04/07 09:52
PHST- 2022/08/05 00:00 [received]
PHST- 2023/01/26 00:00 [accepted]
PHST- 2023/07/25 06:43 [medline]
PHST- 2023/04/08 06:00 [pubmed]
PHST- 2023/04/07 09:52 [entrez]
PHST- 2023/07/31 00:00 [pmc-release]
AID - 01279778-990000000-00248 [pii]
AID - IJS-D-22-00941 [pii]
AID - 10.1097/JS9.0000000000000264 [doi]
PST - epublish
SO  - Int J Surg. 2023 Jul 1;109(7):1941-1952. doi: 10.1097/JS9.0000000000000264.