Development and validation of a ubiquitin-proteasome system gene signature for prognostic prediction and immune microenvironment evaluation in hepatocellular carcinoma.

BACKGROUND: The ubiquitin proteasome has a major role in the development of many tumors. However, the prognostic importance of ubiquitin proteasome-system genes (UPSGs) in hepatocellular carcinoma (HCC) is not fully defined. METHODS: The TCGA and ICGC datasets were utilized to obtain transcriptional profiling data as well as clinicopathological information about HCC. The 3-UPSGs signature for the TCGA cohort was developed via univariate and LASSO Cox regression analyses. Differential expression of genes was demonstrated by qRT-PCR and immunohistochemistry (IHC). Biological pathways were studied using GSVA and GSEA. Six algorithms were used to compare immune infiltration between the two risk groups. Furthermore, drug sensitivity was measured using the "pRRophetic" R package. The predictive capacity of the 3-UPSGs signature for sensitivity to immunotherapy was also explored. Moreover, we performed a pan-cancer analysis of the 3-UPSGs signature. RESULTS: A risk model containing 3 UPSGs (DCAF13, CDC20 and PSMB5) was developed. IHC and qRT-PCR results showed that signature genes were significantly overexpressed in HCC tissues. The high-risk group had a worse prognosis, with a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), elevated levels of immune checkpoint (IC) expression, as well as increased sensitivity to immunotherapy. The two risk groups also differ in their sensitivity to chemotherapeutic drugs. Furthermore, the three UPSGs may play crucial roles in the progression of multiple types of cancers. CONCLUSION: We created a 3-UPSGs signature to estimate the prognosis of HCC and to assist in individualized treatment.

Development and validation of a vesicle-mediated transport-associated gene signature for predicting prognosis and immune therapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with a poor prognosis. The progression of numerous malignancies has been linked to abnormal vesicle-mediated transport-related gene (VMTRG) expression. The prognostic importance of VMTRGs in HCC is uncertain nonetheless. METHODS: Utilizing HCC data from TCGA and ICGC, we employed univariate cox analysis, unsupervised clustering, and lasso analysis to construct molecular subtypes and prognostic signature of HCC based on the prognostic-associated VMTRGs expression levels. Subsequently, we validated the expression levels of the signature genes. We investigated the probable pathways using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Six methods were utilized to compare immune cell infiltration between two risk groups. Moreover, the "pRRophetic" algorithm was utilized to test the drug sensitivity of both groups. RESULTS: We identified two distinct subtypes with divergent biological behaviors and immune functionality through unsupervised clustering. Subtype C1 demonstrated a poorer prognosis. A prognostic signature incorporating two VMTRGs (KIF2C and RAC1) was formulated. Immunohistochemistry and qRT-PCR analyses unveiled a significant upregulation of these pivotal genes within HCC tissues. The prognosis was worse for the high-risk group, which also had a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), a higher immunological infiltration of CD8 + T cells, a higher expression of immune checkpoints, and enhanced immunotherapy efficacy. These two risk groups also have varied chemotherapy drug sensitivities. CONCLUSIONS: Based on VMTRGs, we have developed a signature that assists in accurate prognosis prediction and formulating personalized treatment strategies for HCC patients.

Selective nickel- and manganese-catalyzed decarboxylative cross coupling of some α,ß-unsaturated carboxylic acids with cyclic ethers.

A nickel- and manganese-catalyzed decarboxylative cross coupling of α, ß-unsaturated carboxylic acids with cyclic ethers such as tetrahydrofuran and 1, 4-dioxane was developed. Oxyalkylation was achieved when nickel acetate was used as catalyst, while manganese acetate promoted the reaction of alkenylation.