PARProceedings of Anticancer Research2208-35452208-3553Bio-Byword Scientific Publishing Pty. Ltd.10.26689/par.v9i3.10761ArticleHSP70 is the Most Significantly Upregulated Molecule Upon Bortezomib Stimulation: A Study Based on the Multiple Myeloma Databasehttps://artdesignp.com/journal/PAR/9/3/10.26689/par.v9i3.10761HuangLingjuan,LiRuihua,DaiJinqian2025932025-06-05Objective: This study aimed to investigate the changes in gene expression profiles of multiple myeloma (MM) cells after bortezomib treatment by analyzing the GEO database, thereby providing a theoretical foundation for subsequent research on HSP70. Methods: The GSE41929 dataset was selected from the GEO database. Screening and analysis were performed to identify differentially expressed genes between bortezomib-treated and non-treated MM cells. Results: After bortezomib treatment, 126 genes in MM cells showed the most significant changes in expression (P < 0.05, absolute value of logFC ≥ 1.5). Based on the fold change and the most significant gene module, HSPA1B exhibited the most notable upregulation after HMOX1, followed by HSPA6 and DNAJB1. HSPA1B and HSPA6 are members of the HSP70 protein family, while DNAJB1 primarily interacts with HSP70 to stimulate its ATPase activity and negatively regulates the transcriptional activity of HSF1 induced by heat shock. Conclusion: HSP70 was the most significantly upregulated molecule in MM cells following bortezomib stimulation.

Pirzaman AT, Ebrahimi P, Hasanpour AH, et al., 2023, miRNAs and Multiple Myeloma: Focus on the Pathogenesis, Prognosis, and Drug Resistance. Technol Cancer Res Treat, 22: 1–13.

Dhodapkar MV, 2024, Immune Pathogenesis of Myeloma. Hematol Oncol Clin North Am, 38(2): 281–291.

Gau Y, Yeh T, Hsu C, et al., 2022, Pathogenesis and Treatment of Myeloma-related Bone Disease. Int J Mol Sci, 23(6): 3112.

Hatic H, Inselman S, Inselman J, et al., 2022, Time to First Treatment is an Independent Prognostic Factor For Multiple Myeloma (MM). Leuk Res, 123: 106966.

Mimura N, Hideshima T, Anderson KC, 2015, Novel Therapeutic Strategies for Multiple Myeloma. Exp Hematol, 43(8): 732–741.

Yang Y, Li Y, Gu H, et al., 2020, Emerging Agents and Regimens for Multiple Myeloma. J Hematol Oncol, 13(1): 150.

Bazarbachi AH, Al Hamed R, Malard F, et al., 2022, Induction Therapy Before Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma: An Update. Blood Cancer J, 12(3): 47.

Facon T, San-Miguel J, Dimopoulos MA, et al., 2022, Treatment Regimens for Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis. Adv Ther, 39(8): 3868–3869.

Robak P, Drozdz I, Szemraj J, et al., 2018, Drug Resistance in Multiple Myeloma. Cancer Treat Rev, 70: 199–208.

Vo JN, Wu Y, Mishler J, et al., 2022, The genetic heterogeneity and Drug Resistance Mechanisms of Relapsed Refractory Multiple Myeloma. Nat Commun, 13(1): 3750.

Mikhael JR, Dingli D, Roy V, et al., 2013, Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013. Mayo Clinic Proceedings, 88(4): 360–376.

Jiang H, Wang Y, Wang J, et al., 2022, Posttranslational Modification of Aurora A-NSD2 Loop Contributes to Drug Resistance in t(4;14) Multiple Myeloma. Clin Transl Med, 12(4): e744.

Wang G, Fan F, Sun C, et al., 2022, Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma? Cancers (Basel), 14(21): 5340.

Kubicki T, Bednarek K, Kostrzewska-Poczekaj M, et al., 2022, Bortezomib and Carfilzomib Resistant Myeloma Cells Show Increased Activity of All Three Arms of the Unfolded Protein Response. Am J Cancer Res, 12(7): 3280–3293.

Ferguson ID, Lin Y, Lam C, et al., 2022, Allosteric HSP70 Inhibitors Perturb Mitochondrial Proteostasis and Overcome Proteasome Inhibitor Resistance in Multiple Myeloma. Cell Chem Biol., 29(8): 1288–1302.

Richardson PG, Weller E, Lonial S, et al., 2010, Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy in Patients with Newly Diagnosed Multiple Myeloma. Blood, 116(5): 679–686.

Cavenagh J, Oakervee H, Baetiong-Caguioa P, et al., 2017, A Phase I/II Study of KW-2478, an HSP90 Inhibitor, in Combination with Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma. British Journal of Cancer, 117(9): 1295–1302.

Heinrich JC, Donakonda S, Haupt VJ, et al., 2016, New HSP27 Inhibitors Efficiently Suppress Drug Resistance Development in Cancer Cells. Oncotarget, 7(42): 68156–68169.

Albakova Z, Armeev GA, Kanevskiy LM, et al., 2020, HSP70 Multi-Functionality in Cancer. Cells, 9(3): 587.

Zhao K, Zhou G, Liu Y, et al., 2023, HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances. Biomolecules, 13(4): 601.