Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)
Ling Zhong,
Peng Hao,
Qian Zhang,
Tao Jiang,
Huan Li,
Jialing Xiao,
Chenglong Li,
Lan Luo,
Chunbao Xie,
Jiang Hu,
Liang Wang,
Yuping Liu,
Yi Shi,
Wei Zhang,
Bo Gong
Affiliations
Ling Zhong
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, China
Peng Hao
Department of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Qian Zhang
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Tao Jiang
Department of hematology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Jialing Xiao
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Chenglong Li
Department of hematology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Lan Luo
Chengdu University of Traditional Chinese Medicine, Chengdu, China
Chunbao Xie
The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Jiang Hu
Department of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Liang Wang
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Yuping Liu
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Yi Shi
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Wei Zhang
Department of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47 and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.
