Survival-Critical Genes Associated with Copy Number Alterations in Lung Adenocarcinoma
| Autor: | Chinthalapally V. Rao, Chao Xu, Yuting Zhang, Hiroshi Yamada, Adam S. Asch, Mudassir Farooqui |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genome instability Cancer Research Biology medicine.disease_cause Article lung tumor 03 medical and health sciences 0302 clinical medicine Immune system Chromosome instability Gene expression tumor heterogeneity medicine Gene RC254-282 Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease genomic instability Leukocyte extravasation female genital diseases and pregnancy complications tumor genomics 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Carcinogenesis |
| Zdroj: | Cancers, Vol 13, Iss 2586, p 2586 (2021) Cancers Volume 13 Issue 11 |
| ISSN: | 2072-6694 |
| Popis: | Chromosome Instability (CIN) in tumors affects carcinogenesis, drug resistance, and recurrence/prognosis. Thus, it has a high impact on outcomes in clinic. However, how CIN occurs in human tumors remains elusive. Although cells with CIN (i.e., pre/early cancer cells) are proposed to be removed by apoptosis and/or a surveillance mechanism, this surveillance mechanism is poorly understood. Here we employed a novel data-mining strategy (Gene Expression to Copy Number Alterations [CNA] “GE-CNA”) to comprehensively identify 1578 genes that associate with CIN, indicated by genomic CNA as its surrogate marker, in human lung adenocarcinoma. We found that (a) amplification/insertion CNA is facilitated by over-expressions of DNA replication stressor and suppressed by a broad range of immune cells (T-, B-, NK-cells, leukocytes), and (b) deletion CNA is facilitated by over-expressions of mitotic regulator genes and suppressed predominantly by leukocytes guided by leukocyte extravasation signaling. Among the 39 CNA- and survival-associated genes, the purine metabolism (PPAT, PAICS), immune-regulating CD4-LCK-MEC2C and CCL14-CCR1 axes, and ALOX5 emerged as survival-critical pathways. These findings revealed a broad role of the immune system in suppressing CIN/CNA and cancer development in lung, and identified components representing potential targets for future chemotherapy, chemoprevention, and immunomodulation approaches for lung adenocarcinoma. |
| Databáze: | OpenAIRE |
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