Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival

Autor: Qing Ye, Justin Hickey, Kathleen Summers, Brianne Falatovich, Marieta Gencheva, Timothy D. Eubank, Alexey V. Ivanov, Nancy Lan Guo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 23, p 14978 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms232314978
Popis: There are currently no effective biomarkers for prognosis and optimal treatment selection to improve non-small cell lung cancer (NSCLC) survival outcomes. This study further validated a seven-gene panel for diagnosis and prognosis of NSCLC using RNA sequencing and proteomic profiles of patient tumors. Within the seven-gene panel, ZNF71 expression combined with dendritic cell activities defined NSCLC patient subgroups (n = 966) with distinct survival outcomes (p = 0.04, Kaplan–Meier analysis). ZNF71 expression was significantly associated with the activities of natural killer cells (p = 0.014) and natural killer T cells (p = 0.003) in NSCLC patient tumors (n = 1016) using Chi-squared tests. Overexpression of ZNF71 resulted in decreased expression of multiple components of the intracellular intrinsic and innate immune systems, including dsRNA and dsDNA sensors. Multi-omics networks of ZNF71 and the intracellular intrinsic and innate immune systems were computed as relevant to NSCLC tumorigenesis, proliferation, and survival using patient clinical information and in-vitro CRISPR-Cas9/RNAi screening data. From these networks, pan-sensitive and pan-resistant genes to 21 NCCN-recommended drugs for treating NSCLC were selected. Based on the gene associations with patient survival and in-vitro CRISPR-Cas9, RNAi, and drug screening data, MEK1/2 inhibitors PD-198306 and U-0126, VEGFR inhibitor ZM-306416, and IGF-1R inhibitor PQ-401 were discovered as potential targeted therapy that may also induce an immune response for treating NSCLC.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje