Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma

• 發表在: Frontiers in Pharmacology
• Main Authors: Zhili Lin, Quanqiang Wang, Ziwei Zheng, Bingxin Zhang, Shujuan Zhou, Dong Zheng, Zixing Chen, Sisi Zheng, Shuxia Zhu, Xinyi Zhang, Enqing Lan, Yu Zhang, Xuanru Lin, Qiang Zhuang, Honglan Qian, Xudong Hu, Yan Zhuang, Zhouxiang Jin, Songfu Jiang, Yongyong Ma
• 格式: Article
• 語言: 英语
• 出版: Frontiers Media S.A. 2024-05-01
• 主題: multiple myeloma; platelet; prognostic gene signature; immune microenvironments; biological functions; sensitivity to chemotherapeutic agents
• 在線閱讀: https://www.frontiersin.org/articles/10.3389/fphar.2024.1377370/full

Background: Significant progress has been achieved in the management of multiple myeloma (MM) by implementing high-dose therapy and stem cell transplantation. Moreover, the prognosis of patients has been enhanced due to the introduction of novel immunomodulatory drugs and the emergence of new targeted therapies. However, predicting the survival rates of patients with multiple myeloma is still tricky. According to recent researches, platelets have a significant impact in affecting the biological activity of tumors and are essential parts of the tumor microenvironment. Nonetheless, it is still unclear how platelet-related genes (PRGs) connect to the prognosis of multiple myeloma.Methods: We analyzed the expression of platelet-related genes and their prognostic value in multiple myeloma patients in this study. We also created a nomogram combining clinical metrics. Furthermore, we investigated disparities in the biological characteristics, immunological microenvironment, and reaction to immunotherapy, along with analyzing the drug susceptibility within diverse risk groups.Results: By using the platelet-related risk model, we were able to predict patients’ prognosis more accurately. Subjects in the high-risk cohort exhibited inferior survival outcomes, both in the training and validation datasets, as compared to those in the low-risk cohort (p < 0.05). Moreover, there were differences in the immunological microenvironments, biological processes, clinical features, and chemotherapeutic drug sensitivity between the groups at high and low risk. Using multivariable Cox regression analyses, platelet-related risk score was shown to be an independent prognostic influence in MM (p < 0.001, hazard ratio (HR) = 2.001%, 95% confidence interval (CI): 1.467–2.730). Furthermore, the capacity to predict survival was further improved when a combined nomogram was utilized. In training cohort, this outperformed the predictive value of International staging system (ISS) alone from a 5-years area under curve (AUC) = 0.668 (95% CI: 0.611–0.725) to an AUC = 0.721 (95% CI: 0.665–0.778).Conclusion: Our study revealed the potential benefits of PRGs in terms of survival prognosis of MM patients. Furthermore, we verified its potential as a drug target for MM patients. These findings open up novel possibilities for prognostic evaluation and treatment choices for MM.