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Multicenter Study
. 2025 Sep;32(9):6477-6491.
doi: 10.1245/s10434-025-17289-7. Epub 2025 May 2.

Blood Group Antigen Expression in Blood and Tumor in Relation to Survival Outcomes in Resected Pancreatic Cancer, Overall and by Adjuvant Chemotherapy Regimens

Yosuke Inoue #  1 , Manabu Takamatsu #  2   3 , Yohei Masugi #  4   5 , Tatsunori Suzuki #  6 , Tsuyoshi Hamada  7   8 , Satoru Abe  9 , Kensuke Hara  4 , Yoshikuni Kawaguchi  9 , Kosuke Kobayashi  1 , Aya Maekawa  1 , Yousuke Nakai  6   10 , Naoki Sasahira  11 , Tsuyoshi Takeda  11 , Mariko Tanaka  12 , Yosuke Uematsu  13 , Sho Uemura  13 , Tetsuo Ushiku  12 , Mitsuhiro Fujishiro  6 , Kengo Takeuchi  2   3 , Minoru Kitago #  13 , Kiyoshi Hasegawa #  9 , Yu Takahashi #  1 ; GTK Pancreatic Cancer Study Group in Japan
Collaborators, Affiliations
Multicenter Study

Blood Group Antigen Expression in Blood and Tumor in Relation to Survival Outcomes in Resected Pancreatic Cancer, Overall and by Adjuvant Chemotherapy Regimens

Yosuke Inoue et al. Ann Surg Oncol. 2025 Sep.

Abstract

Background: Few comprehensive studies have examined the associations of the ABO blood group with survival outcomes for patients with resected pancreatic cancer, overall and by adjuvant chemotherapy regimens.

Methods: This multicenter study enrolled 1153 patients with resected pancreatic cancer. The hazard ratios (HRs) for disease-free and pancreatic cancer-specific survival were calculated with adjustment for potential confounders, including KRAS mutation and CDKN2A (p16), TP53, and SMAD4 expression, using the Cox proportional hazards regression model. Blood group antigen expression in tumors was immunohistochemically assessed.

Results: The ABO blood group was not associated with disease-free or pancreatic cancer-specific survival (P > 0.90). For pancreatic cancer-specific survival, blood groups A, B, and AB had multivariable HRs of 0.97 (95% confidence interval [CI], 0.81-1.15), 1.03 (95% CI, 0.83-1.26), and 0.99 (95% CI, 0.76-1.30), respectively (vs. O). The associations between ABO blood group and disease-free and pancreatic cancer-specific survival differed according to the adjuvant chemotherapy regimens (Pinteraction = 0.011 and 0.008, respectively). For the patients without chemotherapy, the HRs for disease-free survival were 0.99 (95% CI, 0.69-1.41) for blood group A, 1.65 (95% CI, 1.09-2.48) for blood group B, and 1.79 (95% CI, 1.01-3.17) for blood group AB, (vs. O). For the patients receiving S-1-based chemotherapy, blood group AB (vs. O) exhibited a reverse association (HR, 0.63; 95% CI, 0.39-1.00). Similar interactions were observed when blood group antigen expression in tumors was analyzed.

Conclusions: The ABO blood group is not a prognostic biomarker in resected pancreatic cancer overall but may predict the effectiveness of adjuvant chemotherapy.

Keywords: Blood group antigens; Cohort studies; Mortality; Pancreatectomy; Pancreatic ductal adenocarcinoma.

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Conflict of interest statement

Disclosure: Drs. Masugi and Hamada acknowledge research funding from the Daiichi Sankyo TaNeDS Funding Program. Dr. Sasahira acknowledges scholarship donation to institution and honararia for speakers from Taiho Pharmaceutical. Dr. Takeuchi acknowledges consultancy fees from Nichirei Bioscience, Nippon Shinyaku, and Meiji Seika Pharma; research support from Fujirebio, SONY, and Daiichi Sankyo; honoraria from Eli Lilly, Chugai, Kyowa Kirin, and Janssen; and royalties from Sysmex, AMOY, and Nichirei bioscience. This work was not funded by any of those companies. No other conflicts of interest exist. The remaining authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flow diagram showing selection of patients with resected pancreatic cancer in a multi-institutional cohort. aFor analyses of disease-free survival, the study further excluded 60 patients with a resected metastatic lesion, R2 resection margin, or no available cross-sectional imaging after the index surgery. IHC, immunohistochemistry; IPMN, intraductal papillary mucinous neoplasm; JFCR, Japanese Foundation for Cancer Research; KU, Keio University; PDAC, pancreatic ductal adenocarcinoma; UT, The University of Tokyo
Fig. 2
Fig. 2
Kaplan–Meier curves for disease-free and pancreatic cancer-specific survival times among patients with pancreatic cancer according to the ABO blood group, overall and by adjuvant chemotherapy regimens. a and b. Disease-free and pancreatic cancer-specific survival times, respectively, among all patients. c and d Disease-free and pancreatic cancer-specific survival times, respectively, among patients who received S-1-based adjuvant chemotherapy. e and f Disease-free and pancreatic cancer-specific survival times, respectively, among patients who received gemcitabine-based adjuvant chemotherapy. g and h Disease-free and pancreatic cancer-specific survival times, respectively, among patients who did not receive adjuvant chemotherapy. Survival times are presented as medians (95% confidence intervals). NA, not available
Fig. 2
Fig. 2
Kaplan–Meier curves for disease-free and pancreatic cancer-specific survival times among patients with pancreatic cancer according to the ABO blood group, overall and by adjuvant chemotherapy regimens. a and b. Disease-free and pancreatic cancer-specific survival times, respectively, among all patients. c and d Disease-free and pancreatic cancer-specific survival times, respectively, among patients who received S-1-based adjuvant chemotherapy. e and f Disease-free and pancreatic cancer-specific survival times, respectively, among patients who received gemcitabine-based adjuvant chemotherapy. g and h Disease-free and pancreatic cancer-specific survival times, respectively, among patients who did not receive adjuvant chemotherapy. Survival times are presented as medians (95% confidence intervals). NA, not available
Fig. 3
Fig. 3
Immunohistochemistry analyses of the expression status of blood group antigens A and B in pancreatic cancer. a Case of blood group A and no expression of blood group antigen B in the tumor. b Case of blood group A and aberrant expression of blood group antigen B in the tumor. c Case of blood group B and no expression of blood group antigen A in the tumor. d Case of blood group B and aberrant expression of blood group antigen A in the tumor. e Concordance of blood group antigen expressions in blood and tumor. Scale bars: 500 µm (main image) and 20 µm (inset). H&E, hematoxylin and eosin
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