Pallante Pierlorenzo, Malapelle Umberto, Nacchio Mariantonia, Sgariglia Roberta, Galati Domenico, Capitelli Ludovica, Zanotta Serena, Galgani Mario, Piemonte Erica, Sanduzzi Zamparelli Alessandro, Rea Gaetano, Bocchino Marialuisa
Istituto per l'Endocrinologia e l'Oncologia Sperimentale (IEOS) "G. Salvatore", Consiglio Nazionale delle Ricerche (CNR), 80131 Napoli, Italy.
Dipartimento di Sanità Pubblica, Università Federico II, 80131 Napoli, Italy.
Diagnostics (Basel). 2021 Jul 2;11(7):1202. doi: 10.3390/diagnostics11071202.
Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age- and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease.
液体活检可从血液中分离出循环游离（ccf）DNA，是一种新兴的非侵入性工具，在肿瘤学中广泛用于诊断和预后评估。先前的数据表明，血清cfDNA可区分特发性肺纤维化（IPF）与其他间质性肺疾病。我们的研究旨在测量59例未经治疗且临床稳定的IPF患者血浆中ccfDNA的水平。我们在血浆cfDNA和基因组DNA中寻找与IPF易感性增加相关的MUC5B基因启动子单核苷酸多态性（SNP，rs35705950），以作比较。招募了35名年龄和性别匹配的健康志愿者作为对照组。我们的结果显示，IPF患者中小尺寸ccfDNA片段的浓度显著高于对照组，且与肺功能恶化呈负相关。此外，104 ng/mL的中位数水平可区分轻度疾病患者和病情更严重的患者。在11.8%的IPF患者和8%的对照组中发现了rs35705950多态性，两者无差异。在所有对照样本中均检测到ccfDNA与基因组DNA完全一致，而携带rs35705950多态性的7例IPF病例中有4例（57%）与基因组DNA不一致（占IPF总数的7%）。液体活检是一种合适的工具，在IPF领域的应用前景乐观。与癌症生物学类似，在IPF患者中发现ccfDNA与基因组DNA之间存在一些差异，这表明前者可能传递疾病原发部位存在的特定遗传信息。
