Abstract：
Cancer detection is challenging, especially in patients with unspecific cancer symptoms. Biomarkers could identify patients at high risk of cancer. Prior studies indicate that neutrophil extracellular traps (NETs) are associated with cancer, but also with autoimmune and infectious diseases. The objective of this prospective study was to investigate markers associated with NET formation (nucleosomal citrullinated histone 3 [H3Cit-DNA], cell free DNA [cfDNA] and neutrophil elastase [NE]), and c-reactive protein (CRP) in patients with unspecific cancer symptoms, such as fatigue, weight loss or radiological sign of malignancy without an apparent primary tumor, referred to the Diagnostic Center at Danderyd Hospital in Sweden. Blood samples were drawn on admission, before cancer diagnosis. Out of 475 patients, 160 (34%) were diagnosed with cancer, 56 (12%) with autoimmune disease, 32 (7%) with infectious disease, 71 (15%) with other diseases and 156 (33%) received no diagnosis. H3Cit-DNA, cfDNA, NE and CRP were significantly higher in patients with cancer compared to patients without cancer (p < 0.0001, p < 0.0001, p = 0.004, and p = 0.0002 respectively). H3Cit-DNA, but not cfDNA, NE or CRP, was significantly elevated in patients with cancer compared to patients with autoimmune disease (p = 0.0001). H3Cit-DNA, cfDNA, NE or CRP did not differ between cancer and infectious disease. In conclusion, H3Cit-DNA is elevated in patients diagnosed with cancer compared to non-cancer patients with the same symptomatology. Further studies should evaluate if H3Cit-DNA could aid in selecting patients that would benefit the most from a rapid cancer diagnostic work-up.
摘要：
癌症检测具有挑战性，尤其是有非特异性癌症症状的患者。生物标志物可以识别癌症高风险患者。先前的研究表明，中性粒细胞胞外陷阱（NETs）与癌症有关，但也有自身免疫性和感染性疾病。这项前瞻性研究的目的是研究与NET形成相关的标记（核小体瓜氨酸化组蛋白3[H3Cit-DNA]，无细胞DNA[cfDNA]和中性粒细胞弹性蛋白酶[NE]），和C反应蛋白（CRP）患者的非特异性癌症症状，比如疲劳，体重减轻或恶性肿瘤的放射学征象，没有明显的原发性肿瘤，提到瑞典Danderyd医院的诊断中心。入院时抽取血样,在癌症诊断之前。在475名患者中，160人（34%）被诊断为癌症，56（12％）患有自身免疫性疾病，32（7％）患有传染病，71例（15%）患有其他疾病，156例（33%）未获得诊断。H3Cit-DNA,cfDNA,与没有癌症的患者相比，癌症患者的NE和CRP明显更高（分别为p<0.0001，p<0.0001，p=0.004和p=0.0002）。H3Cit-DNA,但不是cfDNA，NE或CRP，与自身免疫性疾病患者相比，癌症患者显着升高（p=0.0001）。H3Cit-DNA,cfDNA,NE或CRP在癌症和感染性疾病之间没有差异。总之,与具有相同症状的非癌症患者相比，诊断为癌症的患者的H3Cit-DNA升高。进一步的研究应该评估H3Cit-DNA是否可以帮助选择从快速癌症诊断检查中受益最大的患者。
