What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.

BACKGROUND: Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures. AIM: To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research. METHODS: We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide. RESULTS: Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence. CONCLUSION: Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

Overexpression of cyclin-dependent kinase 1 in esophageal squamous cell carcinoma and its clinical significance.

Cyclin-dependent kinase 1 (CDK1) plays a significant role in certain malignancies. However, it remains unclear whether CDK1 plays a role in esophageal squamous cell carcinoma (ESCC). The aim of this study was to analyze the expression and clinical value of CDK1 in ESCC. CDK1 protein in 151 ESCC tissues and 138 normal esophageal tissues was detected by immunohistochemistry. RNA-seq of eight pairs of ESCC and adjacent esophageal specimens was performed to evaluate the levels of CDK1 mRNA. Microarray and external RNA-seq data from 664 cases of ESCC and 1733 cases of control tissues were used to verify the difference in CDK1 expression between the two groups. A comprehensive analysis of all data was performed to evaluate the difference in CDK1 between ESCC tissues and control tissues. Further, functional enrichment analyses were performed based on differentially expressed genes (DEGs) of ESCC and co-expressed genes (CEGs) of CDK1. In addition, a lncRNA-miRNA-CDK1 network was constructed. The expression of CDK1 protein was obviously increased in ESCC tissues (3.540 ± 2.923 vs. 1.040 ± 1.632, P < 0.001). RNA-seq indicated that the mRNA level of CDK1 was also highly expressed in ESCC tissues (5.261 ± 0.703 vs. 2.229 ± 1.161, P < 0.0001). Comprehensive analysis revealed consistent up-regulation of CDK1 (SMD = 1.41; 95% CI 1.00-1.83). Further, functional enrichment analyses revealed that the functions of these genes were mainly concentrated in the cell cycle. A triple regulatory network of PVT1-hsa-miR-145-5p/hsa-miR-30c-5p-CDK1 was constructed using in silico analysis. In summary, overexpression of CDK1 is closely related to ESCC tumorigenesis.

The Clinical Significance and Potential Molecular Mechanism of PTTG1 in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72-1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83-0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein-protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.