{"title":"利用 PIG-A 突变和 CBMN 检测法测量胰腺癌患者血细胞 DNA 损伤:一项试点研究。","authors":"Lucy Nichols, Rachel Lawrence, Hasan Haboubi, Bilal Al-Sarireh, Shareen Doak, Gareth Jenkins","doi":"10.1093/mutage/gead006","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 2","pages":"93-99"},"PeriodicalIF":2.5000,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181792/pdf/","citationCount":"0","resultStr":"{\"title\":\"Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study.\",\"authors\":\"Lucy Nichols, Rachel Lawrence, Hasan Haboubi, Bilal Al-Sarireh, Shareen Doak, Gareth Jenkins\",\"doi\":\"10.1093/mutage/gead006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":18889,\"journal\":{\"name\":\"Mutagenesis\",\"volume\":\"38 2\",\"pages\":\"93-99\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-05-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181792/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutagenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/mutage/gead006\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mutage/gead006","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
尽管在癌症知识和护理方面取得了进展,但胰腺癌仍然是所有实体恶性肿瘤中预后最差的癌症之一。对胰腺癌的研究尚未完全转化为临床改善,因此只有不到1%的患者在确诊后存活10年。患者的这种暗淡前景可以通过早期诊断得到改善。人类红细胞磷脂酰肌醇聚糖 A 类(PIG-A)检测法通过测量细胞外表面的糖基磷脂酰肌醇(GPI)锚定蛋白来监测 X 连锁 PIG-A 基因的突变状态。我们以前曾在食道腺癌患者中发现 PIG-A 基因突变频率升高,鉴于新型胰腺癌生物标记物的迫切需要,我们在此研究胰腺癌队列中是否也会出现这种情况。在我们的试点研究中,胰腺癌患者(30 人)的 PIG-A 突变频率(5.775 × 10-6 (95% CI 4.777-10) 突变/百万)高于非癌症对照组(14 人),后者的红细胞突变频率为 4.211 × 10-6 (95% CI 1.39-5.16) 突变/百万(p = 0.0052)。以每百万人中 4.7 个突变体为临界值,AUROC 为 0.7595,灵敏度为 70%,特异度为 78.57%。使用细胞分裂受阻微核检测法(P = 0.0164)对替代血细胞群中的 DNA 损伤进行二次测量,结果也显示外周淋巴细胞中的 DNA 损伤增加(AUROC = 0.77,灵敏度 = 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,但还需要对这些 DNA 损伤检测进行进一步研究,以评估它们在胰腺癌诊断中的实用性。
Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study.
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.
期刊介绍:
Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.