ABSTRACT
Background: Semaphorin 5B (SEMA5B) has been described to be involved in the development and progression of cancer. However, the potential diagnostic and prognosis roles and its correlation with tumor-infiltrating immune cells in KIRC have not been clearly reported yet. Methods: The mRNA level of SEMA5B was analyzed via the TCGA and GTEx database as well as the CCLE dataset and verified by GSE53757 and GSE40435 datasets. Meanwhile, the protein level of SEMA5B was analyzed by CPTAC and validated by HPA. The diagnostic value of SEMA5B was analyzed according to the TCGA database and validated by GSE53757, GSE46699, and GSE11024 + GSE46699 datasets. Then, the survival analysis was conducted using GEPIA2. R software (v3.6.3) was applied to investigate the relevance between SEMA5B and immune checkpoints and m6A RNA methylation regulator expression. The correlation between SEMA5B and MMRs and DNMT expression and tumor-infiltrating immune cells was explored via TIMER2. Co-expressed genes of SEMA5B were assessed by cBioPortal, and enrichment analysis was conducted by Metascape. The methylation analysis was conducted with MEXPRESS and MethSurv online tools. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of SEMA5B. Results: SEMA5B was significantly upregulated at both the mRNA and protein levels in KIRC. Further analysis demonstrated that the mRNA expression of SEMA5B was significantly correlated with gender, age, T stage, pathologic stage, and histologic grade. High levels of SEMA5B were found to be a favorable prognostic factor and novel diagnostic biomarker for KIRC. SEMA5B expression was shown to be significantly associated with the abundance of immune cells in KIRC. Also, SEMA5B expression was significantly correlated with the abundance of MMR genes, DNMTs, and m6A regulators in KIRC. Enrichment analysis indicated that the co-expressed genes may involve in crosslinking in the extracellular matrix (ECM). GSEA disclosed that SYSTEMIC_LUPUS_ERYTHEMATOSUS and NABA_ECM_REGULATORS were prominently enriched in the SEMA5B low-expression phenotype. Finally, the methylation analysis demonstrated a correlation between hypermethylation of the SEMA5B gene and a poor prognosis in KIRC. Conclusion: Increased SEMA5B expression correlated with immune cell infiltration, which can be served as a favorable prognostic factor and a novel diagnostic biomarker for KIRC.
ABSTRACT
Carbohydrates remobilization in non-leaf organs has a potential association with the formation of cotton yield. However, our understanding of the physiological and molecular mechanisms regulating carbon remobilization during flowering is still limited. The objectives of the study were to: i) evaluate the potential of carbohydrate remobilization in stems and roots to yield formation; ii) unravel the carbon metabolism and transport associated gene expression patterns regulating carbon remobilization. Two cotton lines 4003-6 and 4003-10 were employed to examine leaf photosynthesis, reproductive biomass accumulation, and carbon dynamics in stems and roots during reproductive growth. The results showed that decreasing leaf photosynthetic capacity combined with rapidly increasing reproductive biomass and leaf area index is accompanied by the initiation of carbohydrate remobilization during first flowering to peak flowering. The proportion of sucrose to total nonstructural carbohydrate was also decreased at that period. The upper and lower of stem recorded higher soluble sugars and starch concentrations, respectively compared to the two others. The gross contribution rate of carbon remobilization to seed cotton yield ranged from 2.83% to 7.12%. Key genes and sugar transporters related to starch and sucrose metabolism in the lower stem exhibited significant up- or down-regulated expressions indicating their important roles in carbon reserves remobilization. Three pivotal sugar transporters SWEET1, TMT2, and ERLD5 presented higher transcript levels at peak flowering suggesting more active sugar movement occurring at that stage. The present study provides potential target genes for engineering carbohydrate metabolism and transport to improve the remobilization efficiency of nonstructural carbohydrates.
