Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma

ABSTRACT

Multiple myeloma (MM) is the second most common hematologic malignancy, which primarily occurs in the elderly. Cellular senescence is considered to be closely associated with the occurrence and progression of malignant tumors including MM, and lncRNA can mediate the process of cellular senescence by regulating key signaling pathways such as p53/p21 and p16/RB. However, the role of cellular senescence related lncRNAs (CSRLs) in MM development has never been reported. Herein, we identified 11 CSRLs (AC004918.5, AC103858.1, AC245100.4, ACBD3-AS1, AL441992.2, ATP2A1-AS1, CCDC18-AS1, LINC00996, TMEM161B-AS1, RP11-706O15.1, and SMURF2P1) to build the CSRLs risk model, which was confirmed to be highly associated with overall survival (OS) of MM patients. We further demonstrated the strong prognostic value of the risk model in MM patients receiving different regimens, especially for those with three-drug combination of bortezomib, lenalidomide, and dexamethasone (VRd) as first-line therapy. Not only that, our risk model also excels in predicting the OS of MM patients at 1, 2, and 3 years. In order to verify the function of these CSRLs in MM, we selected the lncRNA ATP2A1-AS1 which presented the largest expression difference between high-risk groups and low-risk groups for subsequent analysis and validation. Finally, we found that down-regulation of ATP2A1-AS1 can promote cellular senescence in MM cell lines. In conclusion, the CSRLs risk model established in present study provides a novel and more accurate method for predicting MM patients’ prognosis and identifies a new target for MM therapeutic intervention.

KEYWORDS:

• Multiple myeloma
• cellular senescence
• lncRNA
• bioinformatics
• prognosis

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

Xijun Liang and Jin Ding designed the study and were responsible for the overall direction of the study. Tanlun Zeng, Sihan Jiang, and Guanqun Sun performed the experiments. Tanlun Zeng and Guanqun Sun were responsible for editing manuscript and figures. Sihan Jiang and Tanlun Zeng performed bioinformatics analysis and revised the manuscript. Jinjin Cao and Dingtao Hu helped revise the manuscript. Yichuan Wang was responsible for figure modification, data collection and data analysis in the revised manuscript. Jin Ding, Juan Du, Xijun Liang, and Guang Wang made critical revisions and proofread the manuscript. All the authors have read and agreed to submit the final version of the manuscript.

Data availability statement

Publicly available datasets were analyzed in this study. These data can be found here: CellAge (https://genomics.senescence.info/cells/), TCGA (https://portal.gdc.cancer.gov), UCSC Xena platform (https://xenabrowser.net), MMRF researcher gateway portal (https://research.themmrf.org).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2213926.

Additional information

Funding

This study was supported by National Natural Science Foundation of China (82202912), the Sailing project (22YF1458800) from the Science and Technology Commission of Shanghai Municipality, and Youth Startup Fund of the Naval Medical University (2021QN19).