Fig. 1: B cell receptor (BCR)/immunoglobulin repertoire profiles and clinicopathological factors.

a Shared CDR3 amino acid sequences across 102 GC individuals. A total of 102 GC cases (N/T) are plotted along the x axis; then, unique CDR3s with more than 5000 sequence reads among the 102 cases (N + T) are sorted in ascending lexicographical order based on the number of sequence reads in each sample. The color scale indicates the number of sequence reads. Cases #1 to #30 were analyzed in our previous study⁹. b BCR entropy (y-axis) is plotted according to the mutation burdens of the GCs (x-axis). Colors indicate GC subtypes, as indicated. Mutation burdens and hypermutator GCs were defined in our previous report¹⁰. EBV, Epstein-Barr virus-associated GC. c The y-axis indicates the BCR entropy in GC groups with lower and higher mutation burdens as separated by the median of mutation burdens (2.22 SNV/Mb). Center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; dots, outliers. P-value was calculated using the Mann–Whitney U test. d Mutation burdens (left) and BCR entropies (right) are plotted according to the GC subgroups, as indicated. DGC: diffuse-type GC; IGC: intestinal-type GC; Hyper: hypermutator. Ns indicate the number of cases. Center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; dots, outliers. P-values were calculated using the Mann–Whitney U test. e The overall clinical outcomes of the GC patients were analyzed in terms of BCR entropies in the tumor environments. The Kaplan–Meier method indicated that GC cases with BCR entropies higher than the median (88.5 and 54.5 for stage I/II and stage III/IV cases, respectively) exhibited significantly worse prognosis among stage III/IV advanced cases. Multivariate analysis with backward stepwise selection revealed that BCR entropy, together with M classification, is an independent prognostic factor of the overall survival of patients with advanced GC.