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ARTICLE

Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects

QIAN HU, MENGYAO WANG, JINJIN WANG, YALI TAO, TING NIU^*

Department of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, China

* Corresponding Author: TING NIU. Email:

(This article belongs to the Special Issue: Transcriptome Analysis in Tumor Microenvironment and Tumor Heterogeneity)

Oncology Research 2024, 32(4), 753-768. https://doi.org/10.32604/or.2023.043647

Received 08 July 2023; Accepted 23 October 2023; Issue published 20 March 2024

Abstract

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

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Supplementary Material

Supplementary Material File

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