Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom.
Department of Pancreato-biliary surgery, Morriston Hospital, Swansea, United Kingdom.
Mutagenesis. 2023 May 12;38(2):93-99. doi: 10.1093/mutage/gead006.
Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10-6 (95% CI 4.777-10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10-6 (95% CI 1.39-5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.
胰腺癌仍然是所有实体恶性肿瘤中预后最差的肿瘤之一，尽管癌症知识和治疗方面取得了进展。对胰腺癌的研究尚未完全转化为临床改善，因此，不到 1%的患者在诊断后能存活 10 年。通过早期诊断，患者的前景可能会有所改善。人类红细胞磷酸肌醇聚糖 A （PIG-A）检测通过测量细胞外表面的糖基磷脂酰肌醇（GPI）锚定蛋白，监测 X 连锁 PIG-A 基因突变状态。我们之前在食管腺癌患者中发现了升高的 PIG-A 突变频率，鉴于对新型胰腺癌生物标志物的迫切需求，我们在此研究是否可以在胰腺癌患者中看到这种情况。在我们的初步研究中，与非癌症对照组（n = 14）相比，胰腺癌患者（n = 30）的红细胞突变频率（5.775×10-6（95%CI 4.777-10）突变体/百万）升高，非癌症对照组的红细胞突变频率为 4.211×10-6（95%CI 1.39-5.16）突变体/百万（p = 0.0052）。突变体 4.7 个/百万的截值提供了 0.7595 的 AUROC，敏感性为 70%，特异性为 78.57%。使用细胞分裂阻断微核试验，替代血液细胞群中的 DNA 损伤的次要测量值也显示外周淋巴细胞增加（p = 0.0164）（AUROC = 0.77，敏感性 = 72.22%，特异性 = 72.73%）。微核频率和 PIG-A 状态显示出作为胰腺癌血液生物标志物的一些潜力，但需要进一步研究这些 DNA 损伤试验，以评估它们在胰腺癌诊断中的效用。
