Background MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). Methods Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. Results MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. Conclusion MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.

Objective. We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. Methods. We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. Results. E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3–6 and E2F1–8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. Conclusion. E2F1–8 and E2F2–8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3–6 and E2F1–8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.

No abstract

Background: CXCL13 is an important chemotactic factor closely related to the biology of cancer cells. The presence work focused on exploring the significance of CXCL13 in prognosis prediction and analyzing the associations of CXCL13 with T cell function and immune infiltration in various cancers, especially ovarian cancer (OV).Purpose: CXCL13 is associated with prognosis, immune infiltration, and T cell failure of ovarian cancer.Methods: The Oncomine, GEPIA2 and HPA databases were utilized for analyzing CXCL13 levels within diverse cancers. The significance of CXCL13 in prognosis prediction was explored through Kaplan-Meier Plotter, TCGAportal, and GEPIA2. Meanwhile, the associations of CXCL13 with clinical stage, gene marker sets, and immune infiltration were examined through TISIDB, GEPIA2, and TIMER databases. Besides, CXCL13 was screened to analyze the biological processes (BPs) and KEGGs enriched by co-expression genes. The miRWalk database was employed for analyzing the gene-miRNA interaction network of CXCL13 within OV.Results: CXCL13 expression decreased in many cancers, which predicted the dismal survival of OV. CXCL13 upregulation was in direct proportion to the increased immune infiltration degrees of many functional T cells (like exhausted T cells) and immune cells. Additionally, some critical genes of exhausted T cells, such as TIM-3, PD-1, LAG3, TIGIT, GZMB, and CXCL13, were closely associated with CXCL13. Moreover, CXCL13 was related to immune response regulatory signaling pathway, leukocyte cell-cell adhesion, cell adhesion molecules (CAMs), and hematopoietic cell lineage. Conclusion: CXCL13 can serve as a biomarker to predict cancer prognosis, particularly OV. CXCL13 upregulation remarkably elevates the immune infiltration degrees of numerous immune cells, like mast cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, CXCL13 is suggested to be closely related to exhausted T cells, which may be used as a candidate regulating factor for T cell exhaustion within OV. Detecting CXCL13 levels contributes to prognosis prediction and CXCL13 regulation within exhausted T cells, which provides a new approach to maximizing the anti-OV efficacy of immunotherapy.

Background: Lysosomal protein placenta-specific 8 (PLAC8) with abundant cysteine, also referred to as onzin, participates in numerous cancers, and its effect is greatly determined by the cellular and tumor microenvironment (TME). Ourstudy focused on investigating the prognostic significance of PLAC8 and examined the association between PLAC8, immune infiltration, and T cells function in multiple malignancies comprehensively, particularly in breast cancer (BRCA).Methods: PLAC8 expression in various malignancies was analyzed using TIMER. PrognoScan, Kaplan-Meier Plotter, and GEPIA2 were utilized to explore the significance of PLAC8 in prognostic prediction. Moreover, PLAC8 functions were systematically analyzed through cancerSEA. Additionally, TISIDB, TIMER, and GEPIA2 were also employed for analyzing the associations among PLAC8, immune infiltration, related gene marker sets, and clinical stages. Finally, PLAC8 and its co-expressed genes biological process and KEGG were analyzed. Results: PLAC8 expression decreased in most malignancies and was related to poor prognosis in BRCA. PLAC8 significantly affected the survival of BRCA with ER status – array, PR status – IHC, HER2 status – array, Intrinsic subtype, Grade, and Pietenpol subtype. Increased PLAC8 expression positively correlated with the increased immune infiltration levels within immune cells and many functional T cells (such as exhausted T cells). In BRCA cells, PLAC8 functional phenotypesshowed a negative correlation with invasion, metastasis, apoptosis, DNA damage, and DNA repair. Besides, PD-1, TIM-3, TIGIT, LAG3, and GZMB, critical genes of exhausted T cells, interacted with PLAC8. Further analysis indicated that PLAC8 was related to T cell activation, proliferation and adhesion of leukocytes,adaptive immune response, cell adhesion molecules (CAMs), cytotoxicity-mediated by natural killer cells, and the NF-kappa B signal transduction pathway.Conclusion:PLAC8 is a prognostic indicator in pan-cancers, especially BRCA. Elevated PLAC8 level could significantly enhance immune infiltration in CD4+ T cells, CD8+ T cells, and functional T cells. Additionally, PLAC8 was tightly associatedwith T cell exhaustion which possibly enhances the latterwithin BRCA. PLAC8 expression determination might help in prognosis, and modulation of PLAC8level within exhausted T cells, a novel approach for optimizing the therapeutic effect of immunotherapy on BRCA cases.