Long-Term Transcriptomic Reprogramming in Peripheral Blood Mononuclear Cells of Severe COVID-19 Survivors Reveals Pro-Oncogenic Signatures and Cancer-Associated Hub Genes
Duru Cetinkaya P. Kayalar O. Eldem V. Argun Baris S. Kokturk N. Kuralay S.C. Rajabi H. Konyalilar N. Mortazavi D. Korkunc S.K. Erkan S. Aksoy G.T. Eyikudamaci G. Pinar Deniz P. Baydar Toprak O. Yildiz Gulhan P. Sagcan G. Kose Kabil N. Tomruk Erdem A. Fakili F. Ozturk O. Basyigit I. Boyaci H. Azak E. Ulukavak Ciftci T. Oguzulgen I.K. Ozger H.S. Aysert Yildiz P. Hanta I. Ataoglu O. Ercelik M. Cuhadaroglu C. Kuzu Okur H. Tor M.M. Nurlu Temel E. Kul S. Tutuncu Y. Itil O. Bayram H.
December 2025Multidisciplinary Digital Publishing Institute (MDPI)
Viruses
2025#17Issue 12
This study examined the long-term transcriptomic reprogramming in peripheral blood mononuclear cells (PBMCs) of severe COVID-19 patients and its effects for cancer development. RNA sequencing was conducted on PBMCs obtained from healthy controls, COVID-19 patients without pneumonia, and COVID-19 patients exhibiting severe pneumonia one year post-infection. Differential gene expression analysis identified a sustained pro-oncogenic molecular signature, especially among severe COVID-19 patients. Functional enrichment analysis revealed a substantial enrichment of cancer-associated pathways, encompassing apoptosis, viral carcinogenesis, and transcriptional dysregulation. Notably, the autophagy-related gene SQSTM1/P62 was recognized as a distinctive hub gene within the severe COVID-19 patients, interacting with pivotal genes associated with inflammation, apoptosis, and cancer advancement. Survival analysis demonstrated that elevated expression of COVID-19-associated hub genes correlated with unfavorable prognosis in various cancer types, including adrenocortical carcinoma, bladder urothelial carcinoma, and brain lower-grade glioma. These findings indicate that severe COVID-19 infection may establish a systemic milieu favorable to cancer development or recurrence, highlighting the necessity of prolonged oncological monitoring in these patients. Finding specific molecular targets and pathways can help us understand how COVID-19 might be linked to a higher risk of cancer.
bioinformatics analysis , cancer risk , COVID-19 , differentially expressed genes , long-term effects , PBMCs , transcriptomics
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Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana, 01790, Turkey
Department of Biology, Faculty of Arts and Sciences, Cukurova University, Adana, 01790, Turkey
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul, 34010, Turkey
Department of Biology, Science Faculty, Istanbul University, Istanbul, 34134, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli, 41380, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara, 06500, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce, 81620, Turkey
Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul, 34662, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Yalova University, Yalova, 77200, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, 67100, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Gaziantep University, Gaziantep, 27310, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta, 32260, Turkey
Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Kocaeli University, Kocaeli, 41380, Turkey
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara, 06500, Turkey
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Suleyman Demirel University, Türkiye, Isparta, 32260, Kazakhstan
Department of Biostatistics, Faculty of Medicine, Gaziantep University, Gaziantep, 27310, Turkey
Department of Immunology, Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul, 34010, Turkey
Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, 35340, Turkey
Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul, 34010, Turkey
Department of Pulmonary Medicine
Department of Biology
Koc University Research Center for Translational Medicine (KUTTAM)
Department of Biology
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Pulmonary Medicine
Department of Infectious Disease and Clinical Microbiology
Department of Infectious Diseases and Clinical Microbiology
Department of Infectious Diseases and Clinical Microbiology
Department of Biostatistics
Department of Immunology
Department of Pulmonary Medicine
Department of Pulmonary Medicine
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