Clinical Significance of Plasma CD9-Positive Exosomes in HIV Seronegative and Seropositive Lung Cancer Patients

Foteinos-Ioannis Dimitrakopoulos; Anastasia E Kottorou; Kristen Rodgers; John Timothy Sherwood; Georgia-Angeliki Koliou; Beverly Lee; Andrew Yang; Julie Renee Brahmer; Stephen B Baylin; Stephen C Yang; Hajime Orita; Alicia Hulbert; Malcolm V Brock

doi:10.3390/cancers13205193

Clinical Significance of Plasma CD9-Positive Exosomes in HIV Seronegative and Seropositive Lung Cancer Patients

Cancers (Basel). 2021 Oct 16;13(20):5193. doi: 10.3390/cancers13205193.

Authors

Foteinos-Ioannis Dimitrakopoulos^{1

2}, Anastasia E Kottorou^{1

2}, Kristen Rodgers¹, John Timothy Sherwood³, Georgia-Angeliki Koliou⁴, Beverly Lee¹, Andrew Yang¹, Julie Renee Brahmer⁵, Stephen B Baylin⁶, Stephen C Yang¹, Hajime Orita⁷, Alicia Hulbert^{1

6

8}, Malcolm V Brock¹

Affiliations

¹ Division of Thoracic Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
² Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
³ Mary Washington Hospital Center, Fredericksburg, VA 22401, USA.
⁴ Section of Biostatistics, Data Office, Hellenic Cooperative Oncology Group (HECOG), 11526 Athens, Greece.
⁵ Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
⁶ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview, Johns Hopkins University, Baltimore, MD 21231, USA.
⁷ Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Tokyo 113-8421, Japan.
⁸ Department of Surgery, The University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.

Abstract

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 (p < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma (p < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer (p = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls (p < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, p < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients (p < 0.001). Finally, higher plasma exosomes were associated both on univariate (p = 0.044), and multivariate analysis (p = 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.

Keywords: CD9; HIV; NSCLC; SCLC; exosomes; lung cancer; prognosis.

Abstract

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