ABSTRACT
Background
Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL).
Methods
We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay.
Results
The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL.
Conclusion
The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.
List of abbreviations
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Author contributions
M Guan, B Tang and Q Zhang performed the data analysis and interpreted the data. H Zhao and L Li contributed to the experiments of this study. H Zhao prepared the draft. B Tang and X Wang performed the visualization and revised the draft. B Tang and X Wang designed the research and supervised all the work. All authors read and approved the final manuscript. All authors agree to take responsibility for the contents of the article and share responsibility to resolve any questions raised about the accuracy or integrity of the published work.
Availability of data and materials
The original datasets that we used can be obtained at Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). If you have any other questions, please contact the corresponding author directly.
Ethical approval
The study was approved by the Ethics Committee of Dalian Medical University (No. 2023–153). Informed consent was obtained from all subjects involved in the study.
Supplementary materials
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2024.2351465