V、D和J免疫球蛋白（IG）基因片段的重组导致氨基酸（AAs）在该位点的互补决定区3（CDR3）编码中有许多变化。因此，癌症患者可能对癌症蛋白酶，例如基质金属蛋白酶2（MMP2）具有不同程度的CDR3 AA结合特异性。在乳腺癌中，MMP2已被发现对转移起到贡献，并用作肿瘤分期的标记。因此，本报告评估了瘤体居民，患者特异性IG CDR3结合亲和力对癌症蛋白酶的假设，即更大的结合亲和力将与更好的预后相关。使用两个独立的生物信息学工具，我们评估了IG CDR3-MMP2结合亲和力在癌症基因组图谱乳腺癌（TCGA-BRCA）数据集中的分布。结果表明，CDR3-MMP2结合越好，生存概率越高。类似地，对于四个其他蛋白酶，包括卡朋蛋白酶-1和热降解酶，评估结果没有发现与生存概率的相关性。该研究符合患者IG-癌症蛋白酶相互作用可能影响结果的可能性，并引发了一个问题，即治疗性抗体靶向MMP2是否会降低乳腺癌介导的组织破坏和乳腺癌死亡率。版权所有©2023年，国际抗癌研究所（George J. Delinasios博士）。

The recombination of V, D, and J immunoglobulin (IG) gene segments leads to many variations in the amino acids (AAs) encoded at that site, the complementarity determining region-3 (CDR3). Thus, cancer patients may have varying degrees of CDR3 AA binding specificity for cancer proteases, for example, matrix metalloproteinase 2 (MMP2). MMP2 in breast cancer has been found to contribute to metastasis and is used as a marker for tumor staging. Thus, this report evaluated the tumor resident, patient specific IG CDR3 binding affinities to cancer proteases to test the hypothesis that greater binding affinities would be associated with a better outcome.Using two independent bioinformatics tools, we evaluated the IG CDR3-MMP2 binding affinities throughout the cancer genome atlas breast cancer (TCGA-BRCA) dataset.Results indicated that the better the CDR3-MMP2 binding, the better the survival probability. An analogous evaluation for four other proteases, including calpain-1 and thermolysin, displayed no such associations with survival probabilities.This study is consistent with the possibility that patient IG-cancer protease interactions could impact outcomes and raises the question of whether therapeutic antibody targeting of MMP2 would reduce breast cancer mediated tissue destruction and breast cancer mortality rates.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.