Background: Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods: Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results: The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1. Conclusion: CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.

An immune imbalance in the cytokine profile exerts a profound influence on the progression of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). The present study evaluated the immune status of T helper (Th) 17 and Th1 cells in patients with HBV-related and non-HBV-related HCC. We randomly enrolled 150 patients with HCC. Blood samples and tissue samples were obtained. The distributions and phenotypic features of Th17 and Th1 cells were determined by flow cytometry and/or immunohistochemistry. Compared to corresponding non-tumor regions, the levels of Th17 and Th1 cells were significantly increased in tumors of patients with HCC (P<0.001). The intratumoral densities of IL-17-producing cells and IFN-γ-producing cells were associated with overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.001) of patients with HCC. The ratio of Th17 to Th1 in HBV-related HCC was higher than in non-HBV-related HCC. A multivariate Cox analysis revealed that the Th17 to Th1 ratio was an independent prognostic factor for OS (HR = 2.651, P = 0.007) and DFS (HR = 2.456, P = 0.002). HBV infections can lead to an imbalance in immune status in patients with HCC. An elevated Th17 to Th1 ratio may promote tumor progression. The Th17 to Th1 ratio could serve as a potential prognostic marker for scoring the severity of HCC.

The gut microbiome has been recognized as a significant contributor to primary hepatocellular carcinoma (HCC), with mounting evidence indicating associations between bacterial components and cancers of the digestive system. Here, to characterize gut bacterial signature in patients with primary HCC and to assess the diagnostic potential of bacterial taxa for primary HCC, 21 HCC patients and 21 healthy first-degree relatives (control group) were enrolled in this study. Bacterial DNA in the fecal samples was quantified by 16S rRNA gene sequencing. We found that that 743 operational taxonomic units (OTUs) were shared between patients with primary HCC and healthy controls. Of these, 197 OTUs were unique to patients with primary HCC, while 95 OTUs were unique to healthy subjects. Additionally, we observed significant differences in the abundance of Ruminococcaceae_UCG-014 and Romboutsia between patients with primary HCC and their healthy first-degree relatives. Besides, the relative abundance of Ruminococcaceae_UCG-014, and Prevotella_9 was positively correlated with physiological indicators including AST, ALT, ALB, or TBIL. Signature bacterial taxa could serve as non-invasive biomarkers, of which Romboutsia and Veillonella were identified as differential taxa in fecal samples from patients with HCC compared to healthy controls. Romboutsia showed a strong association with HCC (AUC = 0.802). Additionally, the combination of Romboutsia and Veillonella (AUC = 0.812) or the grouping of Fusobacterium, Faccalibacterium, and Peptostreptococcacae together (AUC = 0.762) exhibited promising outcomes for the diagnosis of HCC. The composition of gut microbes in patients with HCC was found to be significantly altered. Differential taxa Romboutsia, Veillonella, and Peptostreptococcacae could be tested for identification of HCC.

Relation between Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-α Expression in Invasive Ductal Breast Cancer Patients and Correlations with Prognosis Ki-67;invasive ductal breast cancer;prognosis; The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.

TRIP13 is a member of the large superfamily of the AAA + ATPase proteins and is associated with a variety of activities. Emerging evidence has shown that TRIP13 may serve as an oncogene. However, the function of TRIP13 in breast cancer (BC) has not yet been elucidated. Here, a variety of bioinformatic tools and laboratory experiments were combined to analyse the expression patterns, prognostic value and functional network of TRIP13 in BC. Multiple databases and immunohistochemistry (IHC) indicated a higher TRIP13 expression in BC tissue compared with normal tissue. TRIP13 was highly expressed in lung metastatic lesions compared with primary tumours in a 4T1 cell implantation BALB/c mouse model of BC. Kaplan–Meier plots also revealed that high TRIP13 expression correlated with poor survival in patients with BC. Furthermore, gene set enrichment analysis revealed that TRIP13 was primarily enriched in the signalling pathway of PI3K‐AKT‐mTOR. Suppressing TRIP13 could inhibit the expression of related genes, as well as the proliferation and migration of BC cell. Finally, 10 hub genes with a high score of connectivity were filtered from the protein–protein interaction (PPI) network, including MAD2L1, CDC20, CDC5L, CDK1, CCNA2, BUB1B, RAD51, SPO11, KIF11 and AURKB. Thus, TRIP13 may be a promising prognostic biomarker and an effective therapeutic target for BC.

Colorectal cancer liver metastases (CRLM) are the primary cause of mortality in colorectal cancer (CRC) patients, highlighting the importance of understanding the underlying mechanisms. The tumor microenvironment (TME) and its interaction with tumor cells play a crucial role in CRLM progression. Notably, the stability and peak levels of tumor-derived exosomal miRNAs facilitate intercellular communication in the TME. Hepatic stellate cells (HSCs), key liver mesenchymal cells, constitute about 33% of the liver's nonsolid cell population and exhibit plasticity. However, the specific role of tumor-derived exosomal miRNAs in the crosstalk between HSCs and tumor cells during the CRLM process remains unclear. We studied CRC-secreted exosomal miR-1246 and its impact on HSCs, as well as its effects on CRC cell proliferation and metastasis. Our findings demonstrate that CRC-secreted exosomal miR-1246 can be internalized by HSCs, leading to their activation and facilitating the metastatic potential of CRC cells. Mechanistically, exosomal miR-1246 targets INSIG1, resulting in SREBP2 nucleation and cholesterol metabolism alterations. This accumulation of free cholesterol (FC) regulates the TLR4/NF-κB/TGF-β pathway, promoting HSC activation. Activated HSCs, in turn, enhance liver metastasis of CRC cells through the TNFSF13/TNFRSF13B axis. Our study reveals the role of CRC-secreted exosomal miR-1246 in triggering HSC activation and reprogramming the TME, ultimately facilitating liver metastasis in CRC patients. Exosomal miR-1246 could serve as a potential non-invasive biomarker for predicting colorectal cancer liver metastasis, enhancing our understanding of CRC-associated liver metastases. Graphical abstract