Gliomas are intensely aggressive and fatal central nervous system (CNS) disorders,which known for their high incidence and mortality rates(14). Standard treatments,such as surgery, radiation therapy and alkylating agent chemotherapy,have yield disappointing results in patients(15). The most effctive surgery strategy to treat glioma is to remove as much brain tissue as possible within a safe incisal edge(16). However,due to the specfic neural functional areas and local infiltration of gliomas,complete removal of the tumor margin is challenging. Hence, there is a pressing requirement to discover more efficacious treatment approaches. In recent years, tumor molecular targeted therapy technology has been speedly developed and has become a new method of treating tumors. Therefore, it is necessary to explore effective and specific glioma molecular markers.
Recently,accumulating evidence demostrating that various cancer cells may be responsible for cancer progression by regulate endogenous H2S-producting anzymes,CBS, and then utilize H2S. In 2017,it was demostrated that stimulation of the CBS/H2S axis facilitates the development of the colon carcinogenesis(17). The current study confirms that breast cancer cells with lower expression of CBS,and its production H2S,plays a substantial role in sustaining bioenergetics,promoting proliferation, growth and facilitating angiogenesis(18).More studies in cancers, such as renal cancer,lung cancer, and ovarian cancer, have not only validated but also expanded upon these findings(19).
In this study,based on mRNA-seq data obtained from the CGGA and TCGA database,we examine the expression of CBS in glioma among a cohort of 1027 samples.We confirme that CBS is enriched in low-grade glioma and acts as a biomarker of GBM. Also, the overall survival of glioma patientsis influenced by CBS.Moreover,we found that CBS is negatively associated with TIL mediated immune response and inflammatory response based on TISIDB and R environmnet.Consistant with previous research, mRNA-seq level of CBS clearly affect the occurrence and development of various tumors.
Furthermore,data from functional studies of glioma based on GO and GSVA revealed that CBS is positvely involved with nervous development,notch pathway and metabolism pathway(4). Through the NF-κB and Akt/ GSK3β pathway,the expression and activity of CBS play a crucial role in significantly alleviating cognitive deficits in individuals with Down syndrome(20).Derease of CBS/H2S level in hunman brain of Alzheimer’s disease (AD)was published(21), the cognitive impairment can be ameliorated by H2S doners through the activation of the PI3/Akt signaling pathway(22).Several reports have also been dedicated to investigating the association between CBS/H2S pathway and notch pathway.A previous study demonstrated that high CBS/H2S sysytem expression facilitates the proliferation of esophageal squamous cell carcinoma (ESCC) via interrupt the Notch1/Hes1 axis(23).
However,there are still some limitations in this study.We did not conduct experimental verification.A previous study showed that mRNA transcription level of CBS,determined by real time PCR assay,was significantly higher in glioma group(24).Also, CBS knockdown in human glioma cells on tumor could promote tumorigensis(25).Undoubtedly,the precision of this study could be greatly enhanced in the future with the development of a new model.In the future,we will delve into the detailed mechanism and function of CBS ,explore more efficient and feasible methods for the treatment of glioma.