Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related deaths worldwide. HCC is a multistep disease marked by various signaling alterations. A better understanding of the new molecular drivers of HCC could therefore provide an opportunity to develop effective diagnostic and therapeutic targets. Ubiquitin-specific protease 44 (USP44), a member of the cysteine protease family, has been reported to play a role in many cancer types. However, its contribution to HCC development remains unknown. In the present study, we observed suppression of USP44 expression in HCC tissue. Clinicopathologic analysis further showed that low USP44 expression correlated with poorer survival and a later tumor stage in HCC, suggesting that USP44 could be a predictor of poor prognosis in patients with HCC. Gain-of-function analysis in vitro demonstrated the importance of USP44 in HCC cell growth and G 0 /G 1 cell cycle arrest. To investigate the downstream targets of USP44 and the molecular mechanisms underlying its regulation of cell proliferation in HCC, we conducted a comparative transcriptomic analysis and identified a cluster of proliferation-related genes, including CCND2 , CCNG2 , and SMC3. Ingenuity Pathway Analysis further delineated the gene networks controlled by USP44 through the regulation of membrane proteins and receptors, enzymes, transcriptional factors, and cyclins involved in the control of cell proliferation, metastasis, and apoptosis in HCC. To summarize, our results highlight, for the first time, the tumor-suppression role of USP44 in HCC and suggest a new prognostic biomarker in this disease.

Section: Discussionmentioning

confidence: 99%

Integrated network findings reveal ubiquitin-specific protease 44 overexpression suppresses tumorigenicity of liver cancer

Zhou,

Yang,

Lin

et al. 2023

“…Previous studies showed that immune cell infiltration affects tumor progression and recurrence while also playing an important role in determining the response to immunotherapy and clinical outcomes [29][30][31]. LUSC is a genetically complex and heterogeneous disorder with no effective therapies.…”

Section: Discussionmentioning

confidence: 99%

Minichromosome maintenance gene family: potential therapeutic targets and prognostic biomarkers for lung squamous cell carcinoma

Yang

Wang

Nie

et al. 2022

Self Cite

The minichromosome maintenance (MCM) gene family comprises of ten members with key roles in eukaryotic DNA replication and are associated with the occurrence and progression of many tumors. However, whether the MCM family contributes to lung squamous cell carcinoma (LUSC) is unclear. In this study, we performed bioinformatic analysis to identify the roles of MCM genes in patients with LUSC. We also evaluated their differential gene expression, prognostic correlation, DNA methylation, functional enrichment of genetic alterations, and immunomodulation. According to the Tumor Immune Estimation Resource database, the expression of MCM2-10 mRNA was elevated in LUSC tissues. According to the Gene Expression Profiling Interactive Analysis database, MCM2-8 and MCM10 were considerably upregulated in LUSC tissues, and protein levels of all MCMs were increased in LUSC tissues. In addition, among the MCM family members, the expression of MCM3 and MCM7 showed the strongest correlation with the prognoses of patients with LUSC. To clarify the role and mechanisms of the MCM family, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment studies were performed. We detected a significant correlation between the expression patterns of MCM family members and infiltrating immune cells. In conclusion, our results improve the understanding of the aberrant expression of MCM family members in LUSC. These findings demonstrate the potential of the MCM family as therapeutic targets and biomarkers for the diagnosis and prognosis of LUSC.

“…The HPA ( https://www.proteinatlas.org/ ) is an online database that contains immunohistochemistry-based expression data for various cancer types [ 43 , 44 ]. In this investigation, we used immunohistochemical images to examine the levels of protein expression of several GATA members in KIRC tumors and normal kidney tissues.…”

Section: Methodsmentioning

confidence: 99%

Expression profile and prognostic values of GATA family members in kidney renal clear cell carcinoma

Yang

Mei

Nie

et al. 2023

Self Cite

To investigate the possible diagnostic and prognostic biomarkers of kidney renal clear cell carcinoma (KIRC), an integrated study of accumulated data was conducted to obtain more reliable information and more feasible measures. Using the Tumor Immune Estimation Resource (TIMER), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter database, Gene Expression Profiling Interactive Analysis (GEPIA2) database, cBioPortal, and Metascape, we analyzed the expression profiles and prognoses of six members of the GATA family in patients with KIRC. Compared to normal samples, KIRC samples showed significantly lower GATA2/3/6 mRNA and protein expression levels. KIRC's pathological grades, clinical stages, and lymph node metastases were closely related to GATA2 and GATA5 levels. Patients with KIRC and high GATA2 and GATA5 expression had better overall survival (OS) and recurrence-free survival (RFS), while those with higher expression of GATA3/4/6 had worse outcomes. The role and underlying mechanisms of the GATA family in cell cycle, cell proliferation, metabolic processes, and other aspects were evaluated based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Furthermore, we found that infiltrating immune cells were highly correlated with GATA expression profiles. These results showed that GATA family members may serve as prognostic biomarkers and therapeutic targets for KIRC.