Differences between Primary Central Nervous System Diffuse Large B-Cell Lymphoma and Its Paraneoplastic Tissues Based on Proteomic Research

Background:

Primary central nervous system lymphoma (PCNSL) is a rare malignant hematologic tumor whose pathophysiological mechanisms are not yet fully understood and which has the clinical characteristics of high aggressiveness, rapid progression, and poor prognosis, making early and rapid diagnosis and timely and effective treatment particularly important. However, the vast majority of oncology studies focus on tumor tissues, and fewer in-depth studies on paraneoplastic tissues. Paraneoplastic tissues are a unique intermediate state between healthy tissues and tumors, and paraneoplastic tissues have certain gene mutations and chromatin copy number variations that may accumulate oncogenic events. Therefore, studying the differences between PCNSL and its paraneoplastic tissues at the proteomic level is important for exploring the pathogenesis of PCNSL and finding potential therapeutic targets.

Purpose:

Through proteomics techniques, the protein characteristics of primary diffuse large B-cell lymphoma of the central nervous system (PCNS DLBCL) and its adjacent tissues were studied on a large scale. Functional enrichment analysis was performed on differentially expressed proteins to explore the pathogenesis of PCNS DLBCL and identify potential therapeutic targets and biomarkers.

Methods:

Surgical resection specimens from 5 patients with PCNS DLBCL were selected as Group A, and 5 specimens of paracancerous tissue paired with them were selected as Group Aa.The samples were then subjected to wax block preparation and HE staining, and the target areas were microdissected using a laser microscope. Specific EP tubes were used for the collection of the cut samples, and the samples of each group were lysed separately by ultrasonic lysis with the addition of lysis buffer, and the supernatants were centrifuged for the determination of protein concentration. An equal amount of protein from each sample was taken for trypsinization and the final concentration was controlled. The samples were then analyzed by EASY-nLC 1200 ultra performance liquid chromatography (UPLC) system coupled with Exactive™ HF-X mass spectrometry. Finally, bioinformatic analysis is performed to obtain a holistic and comprehensive understanding of disease mechanisms, cellular metabolism and other processes at the protein level.

Results:

Good variability between comparison groups and good reproducibility within groups.when the P value < 0.05,a change in differential expression of more than 1.5 was used as the threshold of change for significant up-regulation and less than 1/1.5 was used as the threshold of change for significant down-regulation.By functional enrichment analysis of the differentially expressed proteins (Fc>1.5,p<0.05) between A/Aa, it can be found that the ribosomal pathway is significantly up-regulated, proteins involved in this pathway include upregulated proteins such as MRPS10, RPL39, RPL13A, and RPS21.And there are multiple previous evidences suggesting that over-active ribosomal production promotes growth and value-addition of tumor cells, which is an important factor in cancer development.

Conclusion:

The results of this study indicate that the occurrence of PCNS DLBCL is closely related to the ribosomal pathway, and elevated ribosomal function can promote the rapid growth of tumor cells, therefore, inhibition of ribosome production can be a potential target for the treatment of cancer, ribosome synthesis involves a number of processes, and a large number of genes related to ribosomal production that are closely related to the development of cancer have not yet been fully researched and exploited.Therefore, the search for new therapeutic targets is of great significance. Immunohistochemical testing for correlation validation is in progress.

No relevant conflicts of interest to declare.