Lin Zhili, Wang Quanqiang, Zheng Ziwei, Zhang Bingxin, Zhou Shujuan, Zheng Dong, Chen Zixing, Zheng Sisi, Zhu Shuxia, Zhang Xinyi, Lan Enqing, Zhang Yu, Lin Xuanru, Zhuang Qiang, Qian Honglan, Hu Xudong, Zhuang Yan, Jin Zhouxiang, Jiang Songfu, Ma Yongyong
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2024 May 16;15:1377370. doi: 10.3389/fphar.2024.1377370. eCollection 2024.
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. 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. 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 ( < 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 ( < 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). 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.
通过实施大剂量治疗和干细胞移植,多发性骨髓瘤(MM)的管理取得了显著进展。此外,由于新型免疫调节药物的引入和新靶向治疗方法的出现,患者的预后得到了改善。然而,预测多发性骨髓瘤患者的生存率仍然很棘手。根据最近的研究,血小板在影响肿瘤的生物学活性方面具有重要作用,并且是肿瘤微环境的重要组成部分。尽管如此,血小板相关基因(PRGs)与多发性骨髓瘤预后之间的联系仍不清楚。在本研究中,我们分析了血小板相关基因在多发性骨髓瘤患者中的表达及其预后价值。我们还创建了一个结合临床指标的列线图。此外,我们研究了不同风险组在生物学特征、免疫微环境和免疫治疗反应方面的差异,并分析了药物敏感性。通过使用血小板相关风险模型,我们能够更准确地预测患者的预后。与低风险队列中的受试者相比,高风险队列中的受试者在训练和验证数据集中的生存结果均较差(P<0.05)。此外,高风险组和低风险组之间在免疫微环境、生物学过程、临床特征和化疗药物敏感性方面存在差异。使用多变量Cox回归分析,血小板相关风险评分被证明是MM的独立预后影响因素(P<0.001,风险比(HR)=2.001%,95%置信区间(CI):1.467-2.730)。此外,当使用联合列线图时,预测生存的能力进一步提高。在训练队列中,这一预测价值优于单独的国际分期系统(ISS),5年曲线下面积(AUC)从0.668(95%CI:0.611-0.725)提高到0.721(95%CI:0.665-0.778)。我们的研究揭示了PRGs在MM患者生存预后方面的潜在益处。此外,我们验证了其作为MM患者药物靶点的潜力。这些发现为MM的预后评估和治疗选择开辟了新的可能性。