KEY TAKEAWAYS
- The study aimed to pinpoint key genes and signaling pathways linked to chemotherapy resistance in PTCL patients.
- The results demonstrated that the pivotal genes TNFRSF1B, TRADD2, MAP3K7, and the TNF pathway are downregulated in PTCL chemoresistance, guiding potential therapies.
Peripheral T-cell lymphoma (PTCL) presents as a non-Hodgkin’s lymphoma subtype, primarily manifesting at extranodal locations, often managed through chemotherapy and radiotherapy. Characterized by heightened malignancy compared to other lymphoid tumors, PTCL exhibits a grim prognosis with a high 5-year recurrence rate. Patients facing relapse-resistant disease encounter treatment challenges due to the absence of standardized therapies.
Despite this, understanding the molecular mechanisms driving PTCL cells’ resistance to chemotherapy remains elusive, necessitating the development of strategies to overcome drug resistance.
Yunyi Lan and the team spearheaded a study that aimed to identify the specific genes and signaling pathways linked to chemotherapy resistance in PTCL patients.
The study enrolled 7 clinical patients and 5 healthy controls. Among the patients, 4 were categorized as chemotherapy-sensitive, and 3 as chemotherapy-resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells.
Researchers conducted RNA sequencing on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, they validated the expression patterns of differentially expressed genes (DEGs) associated with the most enriched signaling pathways, focusing on cancer-related genes, using quantitative real-time polymerase chain reaction (qRT-PCR) in PTCL patients.
Results showed 4063 DEGs in PTCL specimens from chemotherapy-resistant patients via RNA-seq analysis, comprising 1128 upregulated and 2935 downregulated genes. Quantitative gene expression analysis confirmed differential expression in all libraries, with 9 downregulated and 10 upregulated genes validated through qRT-PCR in 6 clinical specimens from chemotherapy-resistant patients.
The KEGG pathway analysis identified significant alterations in several pathways, including 6 downregulated and 9 upregulated pathways enriched in the DEGs. The extensively regulated TNF signaling pathway exhibited significant changes, suggesting its crucial role in chemotherapy resistance in PTCL.
The study findings indicated that certain genes, such as TNFRSF1B, TRADD2, and MAP3K7, potentially influence chemotherapy resistance in PTCL. Additionally, the observed downregulation of the TNF signaling pathway, pivotal for cell survival and differentiation, suggests its involvement in chemotherapy resistance development. These insights into molecular mechanisms offer potential targets for overcoming treatment resistance in this challenging disease.
This study received funding from the Yunnan Provincial Department of Science and Technology–Kunming Medical University Joint Special Young Doctoral Program and the National Natural Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38468267/
Lan, Y., Tao, W., Ma, L. et al. (2024) “The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.” BMC Med Genomics 17, 74 (2024). https://doi.org/10.1186/s12920-024-01842-6.
