A new exploration: characterization of the differentiation trajectory of prostate cancer cells.

Prostate cancer is one of the most common malignant tumors in men, and in-depth study of its gene expression patterns is crucial for understanding the formation and development of prostate cancer. Although single-cell transcriptomics has deeply explored the heterogeneous expression characteristics of prostate cancer, given that normal epithelial cells themselves have different states of differentiation, these normal differentiation characteristics may lead to confusion with heterogeneous tumor characteristics. In this study, we used single-cell data from the GEO database to analyze in detail the heterogeneity of prostate cancer tumor cells/tumor-associated epithelium cells (TAECs), with a particular focus on the differentiation state of epithelial cells in matching normal tissue. We found that after subtype pairing analysis of normal tissue and tumor tissue epithelium based on differentiation status, the characteristics identified later were not consistent with the general characteristics originally exhibited by different TAECs subpopulations. Among them, all TAECs subpopulations showed P53 enrichment and downregulation of the apoptotic pathway, and expressed higher levels of EGFR, ERBB2, interferon receptors, MIF, and cell adhesion-related signals; through transcription factor regulatory network analysis, we observed that YY1, NKX3-1, and EHF had higher transcriptional activity in TAECs subpopulations than normal epithelial cells at the same differentiation stage, while ATF3 was the opposite. Among them, YY1 may act as an upstream regulator of the MIF signaling pathway, and ATF3 is a key upstream transcriptional regulator of differentially expressed genes in the P53 and apoptotic pathways. Immune infiltration analysis showed that the above four transcription factors were significantly correlated with the infiltration of immune cells in prostate cancer, and pan-cancer analysis showed that their expression-related survival risks were widely present in different cancers. It is worth noting that this is merely a preliminary, exploratory study, which inevitably has some deficiencies and limitations. Despite this, this study is committed to bringing a novel and unique perspective to the field through this work, with the hope of opening up new levels of understanding and stimulating more in-depth research and discussion.

An integrative pan-cancer analysis reveals the carcinogenic effects of NCAPH in human cancer.

BACKGROUND: Non-chromosomal structure maintenance protein condensin complex I subunit H (NCAPH) has been reported to play a regulatory role in a variety of cancers and is associated with tumor poor prognosis. This study aims to explore the potential role of NCAPH with a view to providing insights on pathologic mechanisms. METHODS: The expression of NCAPH in different tumors was explored by The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx). The prognostic value of NCAPH was retrieved through GEPIA and Kaplan-Meier Plotter databases. Tumor Immunity Estimation Resource (TIMER) and Single-Sample Gene Set Enrichment Analysis (GSEA) to search for the association of NCAPH with tumor immune infiltration. The cBioPortal and PhosphoSite Plus databases showed NCAPH phosphorylation status in tumors. Gene set enrichment analysis (GSEA) was performed using bioinformatics. RESULTS: Our findings revealed that NCAPH showed high expression levels in a wide range of tumor types, and was strongly correlated with the prognosis of patients. Moreover, a higher phosphorylation level at S59, S67, S76, S190, S222 and T38 site was discovered in head and neck squamous cell carcinoma (HNSC). NCAPH overexpression was positively correlated with the infiltration level of CD8+T cells and myeloid dendritic infiltration in breast cancer and thymoma. CONCLUSIONS: The up-regulation of NCAPH was significantly correlated with the poor prognosis and immune infiltration in pan-cancer, and NCAPH could be served as a potential immunotherapeutic target for cancers.

ß-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers.

NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that ß-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of ß-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, ß-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.

[Clinicopathological significance of ezrin and SIX1 protein expression in alpha fetoprotein-negative hepatocellular carcinoma].

OBJECTIVE: To investigate the clinicopathological significance of ezrin and SIX1 overexpression in alpha fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS: The EnVision immunohistochemical method was used to detect the protein expression of ezrin and SIX1 in the tumor tissues and corresponding adjacent normal liver tissues from 50 AFP-negative HCC patients. The correlations between the overexpression of ezrin and SIX1 and the prognosis of the patients with HCC were analyzed by Chi-square test and Spearman analysis. RESULTS: The positive rates of ezrin and SIX1 protein expression in AFP-negative HCC tissues were 68.0% (34/50) and 60.0% (30/50), respectively, and they were significantly higher than the expression rates [38.0% (19/50) and 26.0% (13/50)] in adjacent normal liver tissues. Chi-square test showed that the expression of both ezrin and SIX1 proteins were related to TNM stage and lymphovascular infiltration, and Spearman analysis revealed a positive correlation between ezrin and SIX1 expression in AFP-negative HCC. CONCLUSION: Both Ezrin and SIX1 proteins are highly expressed in AFP-negative HCC, and significantly related with the TNM stage and lymphovascular infiltration of patients with AFP-negative HCC. In addition, there is a positive correlation between ezrin and SIX1 expression in AFP-negative HCC.

Overexpression of sineoculis homeobox homolog 1 predicts poor prognosis of hepatocellular carcinoma.

High expression levels of the human sineoculis homeobox homolog 1 (SIX1) gene have been correlated with numerous human malignancies. The SIX1 protein is involved in chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. This study explores the role of SIX1 in tumor progression and in the prognostic evaluation of hepatocellular carcinoma (HCC). Real-time PCR, Western blotting analysis, immunofluorescence (IF) staining, and immunohistochemistry (IHC) were performed to examine SIX1 expression in HCC cell line/tissues compared with adjacent non-tumor and normal liver tissues. Statistical analysis was applied to evaluate the correlation between SIX1 overexpression and the clinicopathological features of HCC. Survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was analyzed using the Cox proportional hazard models. The SIX1 protein was detected in 80.9% of HCCs, which was significantly higher than that in either adjacent non tumor liver or normal liver tissues (P < 0.01). SIX1 overexpression was positively correlated with tumor size, pTNM stage and venous infiltration. Moreover, the 5-year survival rate of patients with high expression of SIX1 was significantly lower than that of patients with low SIX1 expression. Multivariate analysis suggested that pTNM stage and SIX1 protein expression were independent risk factors for survival in HCC. In conclusion, SIX1 plays an important role in the progression of HCC. High level expression of SIX1 is an independent poor prognostic factor of HCC.