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Peripheral blood transcriptome heterogeneity and prognostic potential in lung cancer revealed by RNA-Seq |
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| Authors: | Qi Zhang Manchao Kuang Haiyin An Yajing Zhang Kai Zhang Lin Feng Lei Zhang Shujun Cheng |
| Affiliation: | 1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Formal analysis (lead), Methodology (lead), Resources (lead), Visualization (lead), Writing - original draft (lead);2. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Data curation (lead), Methodology (equal), Validation (equal);3. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Data curation (equal);4. Department of Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Resources (equal);5. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Supervision (lead), Validation (equal), Writing - review & editing (lead);6. Department of Endoscopy ,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;7. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China |
| Abstract: | Understanding of the complex interaction between the peripheral immune system and lung cancer (LC) remains incomplete, limiting patient benefit. Here, we aimed to characterize the host peripheral immune response to LC and investigate its potential prognostic value. Bulk RNA-sequencing data of peripheral blood leucocytes (PBLs) from healthy volunteers and LC patients (n = 142) were analysed for characterization of host systemic immunity in LC. We observed broad blood transcriptome perturbations in LC patients that were heterogeneous, as two new subtypes were established independent of histology. Functionally, the heterogeneity between the two subtypes included dysregulation of diverse biological processes, such as the cell cycle, blood coagulation and inflammatory signalling pathways, together with the abundance and activity of blood cells, particularly lymphocytes and neutrophils, ultimately manifesting as differences in antitumour immune status. Based on these findings, a prognostic model composed of ten genes dysregulated in one LC subtype with relatively poor immune status was developed and validated in a Gene Expression Omnibus (GEO) data set (n = 108), helping to generate a prognostic nomogram. Collectively, our study provides novel and comprehensive insight into the heterogeneity of the host peripheral immune response to LC. The expression heterogeneity–based predictive model may help guide prognostic management for LC patients. |
| Keywords: | heterogeneity high-throughput sequencing lung cancer peripheral blood leucocytes prognosis |