Does the ABO gene have prognostic value for immunotherapy efficacy?

Abstract

e14656 Background: The potential linkage of ABO blood group with the immune system and cancer risk has been widely studied. However, the value of ABO single nucleotide polymorphisms (SNPs) on the prognosis of immune checkpoint inhibitors (ICIs) treatment remains unclear. Methods: 1. Study population: We included consecutive patients admitted for malignancy to the Second Xiangya Hospital, Central South University in Changsha, China, from May 2016 to April 2022. We collected the blood samples from patients receiving ICIs therapies regardless of treatment lines. 2. Data collection and follow-up method: From the electronic medical record information system, patients’ elements were abstracted and entered into a clinical data sheet.The primary outcome of this study was the efficacy of the ICI treatment. According to RECIST 1.1 criteria, the progression-free survival (PFS) and the overall survival (OS) were used to assess the treatment efficacy. The second outcomes were irAEs, which were assessed and graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE4.0). 3. Candidate SNPs selection: We downloaded the ABO gene sequence in the three prime untranslated regions (3’UTR) of Chinese South population from the 1000 Genomes Project (http://www.1000genomes.org/) and obtained 11 tag SNPs following the above criteria with Haploview 4.2 software. 4. SNP genotyping: Blood samples were collected after enrollment at hospital admission. Genotyping was performed using the SNP Sequenom MassARRAY platform. 5. Statistical analysis: The statistical analysis was applied using SPSS 19.0 (IBM Corp., Armonk, New York, USA) and Plink v1.07 (URL: http://pngu.mgh.harvard.edu/purcell/plink/). Results: Three SNPs, rs9411476, rs61527302, and rs10901251, were strongly associated with progression-free survival (PFS). Cox regression analysis revealed that rs9411476 AA+GA carriers experienced significantly extended PFS ( P -value = 0.006, adjusted HR = 0.62, 95%CI = 0.44-0.87) compared with GG carriers. The rs61527302 GA+AA carriers and rs10901251 AC+CC carriers experienced significantly prolonged PFS compared with rs61527302 GG carriers ( P -value = 0.016, adjusted HR = 0.66, 95%CI = 0.47-0.93) and rs10901251 AA carriers ( P -value = 0.023, adjusted HR = 0.69, 95%CI = 0.50-0.95), respectively. The ABO haplotype analysis revealed that the multiple mutations carriers exhibited significantly prolonged PFS ( P -value = 0.005, adjusted HR = 0.61, 95%CI = 0.44-0.86) than other patients.The ABO multiple mutations haplotype was not associated with the occurrence of overall immune-related adverse events (irAEs) and toxicity in most specific organs. Besides, multiple ABO mutations carriers were less likely to experience diarrhea ( P -value = 0.023). Conclusions: our findings showed that the multiple ABO mutations carriers did not suffer more irAEs while exhibiting better immunotherapy efficacy.