Dimitrakopoulos Foteinos-Ioannis, Kottorou Anastasia E, Rodgers Kristen, Sherwood John Timothy, Koliou Georgia-Angeliki, Lee Beverly, Yang Andrew, Brahmer Julie Renee, Baylin Stephen B, Yang Stephen C, Orita Hajime, Hulbert Alicia, Brock Malcolm V
Division of Thoracic Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
Cancers (Basel). 2021 Oct 16;13(20):5193. doi: 10.3390/cancers13205193.
Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas. Plasma exosome concentrations differed between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer even after chemotherapy ( < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma ( < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer ( = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls ( < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients ( < 0.001). Finally, higher plasma exosomes were associated both on univariate ( = 0.044), and multivariate analysis ( = 0.040) with a better 3-year survival in stage II and III NSCLC (Non-small-cell lung carcinoma) patients. In conclusion, our study shows that CD9-positive plasma exosomes are associated with both lung cancer and HIV, prior chemotherapy, as well as with survival, suggesting a possible prognostic value.
最近，已阐述了外泌体在癌症和HIV（人类免疫缺陷病毒）进展中的作用。本研究调查了CD9阳性血浆外泌体在肺癌患者、健康个体以及患有或未患有肺癌的HIV阳性患者中的临床意义。采用经透射电子显微镜验证的双夹心ELISA技术，从210例肺癌患者（包括44例化疗后疾病进展的转移性患者）、49例健康对照、20例肺肉芽肿患者、19例HIV阳性肺癌患者、31例HIV阳性无癌患者以及3例HIV阳性肺肉芽肿患者中分离并定量血浆来源的外泌体。即使在化疗后，健康对照、免疫功能正常的肺肉芽肿患者和肺癌患者之间的血浆外泌体浓度也存在差异（<0.001）。与未治疗的肺癌患者或肉芽肿患者相比，化疗后的肺癌患者外泌体浓度较低（两者均<0.001）。与HIV阳性肺癌患者相比，HIV阳性无癌患者的外泌体浓度显著更高（=0.016）。尽管所有不同肺癌组织学类型与健康对照之间的外泌体浓度存在差异（所有组织学类型均<0.001），但仅肉芽肿患者和小细胞肺癌（SCLC）患者的调整后统计学显著性得以保留（<0.001）。与免疫功能正常的肉芽肿和肺癌患者相比，患有或未患有肺癌的HIV诱导免疫缺陷患者的血浆外泌体较低（<0.001）。最后，在II期和III期非小细胞肺癌（NSCLC）患者中，较高的血浆外泌体在单变量分析（=0.044）和多变量分析（=0.040）中均与更好的3年生存率相关。总之，我们的研究表明，CD9阳性血浆外泌体与肺癌、HIV、化疗史以及生存率相关，提示其可能具有预后价值。
