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, Pelin; Kayalar, Ozgecan; Eldem, Vahap; Argun Baris, Serap; Kokturk, Nurdan; Kuralay, Selim; Rajabi, Hadi; Konyalilar, Nur; Mortazavi, Deniz; Korkunc, Seval; Erkan, Sinem; Aksoy, Gizem; Eyikudamaci, Gul; Pinar Deniz, Pelin; Baydar Toprak, Oya; Yildiz Gulhan, Pinar; Sagcan, Gulseren; Kose Kabil, Neslihan; Tomruk Erdem, Aysegul; Fakili, Fusun; Ozturk, Onder; Basyigit, Ilknur; Boyaci, Hasim; Azak, Emel; Ulukavak Ciftci, Tansu; Oguzulgen, Ipek; Ozger, Hasan; Aysert Yildiz, Pinar; Hanta, Ismail; Ataoglu, Ozlem; Ercelik, Merve; Cuhadaroglu, Caglar; Kuzu Okur, Hacer; Tor, Muge; Nurlu Temel, Esra; Kul, Seval; Tutuncu, Yıldız; Itil, Oya; Bayram, Hasan

doi:10.3390/v17121608

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., ...More

VIRUSES, vol.17, no.12, pp.1-18, 2025 (Scopus)

Publication Type: Article / Article
Volume: 17 Issue: 12
Publication Date: 2025
Doi Number: 10.3390/v17121608
Journal Name: VIRUSES
Journal Indexes: Scopus, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals
Page Numbers: pp.1-18
Istanbul University Affiliated: Yes

Abstract

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.