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Objective: To analyze the gene expression of coiled-coil domain containing protein 137 (CCDC137) in hepatocellular carcinoma (HCC) tissues and its relationship with clinicopathological features and prognosis of HCC patients, and to explore the effect of CCDC137 knockdown on the proliferation, migration and invasion of MHCC97H cells. Methods: The HCC dataset was downloaded from The Cancer Genome Atlas (TCGA) to obtain the CCDC137 gene expression profile and clinical information of patients. The correlation between the expression level of CCDC137 gene in HCC tissues and the clinicopathological indices and its impact on patients' prognosis were analyzed by bioinformatics method. Gene Set Enrichment Analysis (GSEA) was used to predict the possible pathways regulated by CCDC137 gene in HCC. Kaplan-Meier method and Log-Rank test were used for survival analysis; Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis of patients. The expression of CCDC137 in MHCC97H cells was inhibited by small interfering RNA technology. The mRNA and protein expression levels of CCDC137 in transfected MHCC97H cells as well as its effect on cell proliferation, migration and invasion were observed by qPCR, WB, CCK-8 and Transwell assays, respectively. Results: According to the data of 371 HCC patients retrieved from TCGA database, the expression level of CCDC137 mRNA in tumor tissues was significantly higher than that in the para-cancerous tissues (P<0.01). The high expression of CCDC137 mRNA was significantly correlated with tumor histological grade (OR=0.014), cancer tissue stage (OR=0.007), and T stage (OR=0.047) (all P<0.05). The OS rate of patients with high CCDC137 expression was significantly lower than that of patients with low CCDC137 expression (P<0.05), and multivariate Cox regression analysis suggested that CCDC137 gene could be an independent prognostic factor for HCC patients. GSEA results showed that the samples with high expression of CCDC137 gene were enriched in multiple pathways/gene sets such as base excision repair and spliceosome (P<0.01, FDR<0.05). After knockdown of CCDC137 gene, the proliferation, migration and invasion of MHCC97H cells were significantly decreased (all P<0.01). Conclusion: CCDC137 gene is highly expressed in HCC tissues. The high expression of CCDC137 is related to the occurrence, development and poor prognosis of HCC. Inhibition of CCDC137 gene expression can inhibit the proliferation, migration and invasion of MHCC97H cells. [ABSTRACT FROM AUTHOR]

Hepatobiliary cancers, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the deadliest malignancies worldwide, leading to a significant number of cancer-related deaths. While bone metastases from these cancers are rare, they are highly aggressive and linked to poor prognosis. This review focuses on RNA-based molecular mechanisms that contribute to bone metastasis from hepatobiliary cancers. Specifically, the role of two key factors, microRNAs (miRNAs) and RNA-binding proteins (RBPs), which have not been extensively studied in the context of HCC and CCA, is discussed. These molecules often exhibit abnormal expression in hepatobiliary tumors, influencing cancer cell spread and metastasis by disrupting bone homeostasis, thereby aiding tumor cell migration and survival in the bone microenvironment. This review also discusses potential therapeutic strategies targeting these RNA-based pathways to reduce bone metastasis and improve patient outcomes. Further research is crucial for developing effective miRNA- and RBP-based diagnostic and prognostic biomarkers and treatments to prevent bone metastases in hepatobiliary cancers. [ABSTRACT FROM AUTHOR]

G protein pathway suppressor 1 (GPS1) is involved in the development of many diseases including tumors, but its specific regulatory mechanism in breast cancer is not clear. The goal of the present study was to explore the biological effects and underlying mechanism of GPS1 in breast cancer. Public databases were used to analyze GPS1 expression and the relationship with clinicopathological characteristics and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of GPS1 in breast cancer. Data analysis showed that the expression of GPS1 in breast cancer tissues was significantly higher than that in paracancerous tissues (p < 0.001), and the receiver operating curve (ROC) revealed a higher diagnostic efficiency (AUC = 0.832). Survival analyses indicated that patients with high GPS1 expression made the prognosis worse in Luminal B, low to intermediate-grade breast cancers. Enrichment analysis showed that GPS1 was involved in the formation of ribonucleoprotein complexes, which dynamically altered the fate of RNA; it could also enhance the responsiveness of the Wnt pathway by interacting with WBP2. In addition, GPS1 expression was closely related to the immune microenvironment. GPS1 knockdown inhibits the proliferation, invasion and migration of MCF7 and MDA-MB-231 cells in vitro. This study suggests that the upregulation of GPS1 is associated with the malignant biological behavior and prognosis of breast cancer and may promote cancer progression. The correlation between GPS1 and the immune microenvironment suggests that it may be a potential target for immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BRCA) is a prevalent tumor worldwide. The association between the coiled-coil domain-containing (CCDC) protein family and different tumors has been established. However, the prognostic significance of this protein family in breast cancer remains uncertain. Methods: Gene expression and clinical data were obtained from the TCGA, METABRIC, and GEO databases. Prognosis genes were identified using univariate Cox and LASSO Cox regression, leading to the establishment of a prognostic signature. Subsequently, the risk model was conducted based on survival and clinical feature analyses, and a nomogram for prognosis prediction was developed. Furthermore, analyses of biological function, immune characteristics, and drug sensitivity were performed. Finally, single-cell sequencing data were utilized to uncover the expression patterns of genes in the risk model. Results: Five genes were identified and utilized for risk modeling. The model demonstrated excellent prognostic value as indicated by ROC and Kaplan–Meier analysis. The high-risk group exhibited shorter survival time and higher likelihood of recurrence. Functional annotation indicated a correlation between the risk score and immune pathways. Conversely, the low-risk group displayed a greater enrichment in immune pathways and exhibited more active immune microenvironment characteristics. Additionally, drug sensitivity analysis using both public and our sequencing data revealed that the risk model possessed a broad range of predictive values. Conclusions: We have developed a gene signature and have verified that patients with low-risk are more likely to have better prognosis and respond positively to therapy. This finding offers a valuable point of reference for BRCA individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Coiled-coil domain containing 60 (CCDC60) is a member of the CCDC family, which participates in the progression of many types of cancer. However, the prognostic value of CCDC60 in head and neck squamous cell carcinoma (HNSC) and its function in tumor immunity remain unclear. Methods: CCDC60 expression and its prognostic potential in HNSC were evaluated by bioinformatics approaches, which was validated in human HNSC samples. Genetic alteration analysis of CCDC60 and the underlying biological function of CCDC60 related co-expressed genes in HNSC were analyzed. The impact of CCDC60 on the regulation of immune infiltration in HNSC was comprehensively investigated. In vitro, a series of functional assays on CCDC60 were performed in HNSC cells. Results: Our study has indicated that compared with the adjacent normal tissues, CCDC60 expression was considerably downregulated in HNSC tissues. High CCDC60 expression was connected with favorable outcome of HNSC patients, and its prognostic significance was examined by distinct clinical characteristics. We identified the CCDC60-related co-expression genes, which were mainly enriched in the NOD-like receptor signaling pathway associated with the inhibition of tumor growth, leading to a better prognosis of HNSC patients. In vitro, CCDC60 overexpression significantly inhibited the growth, migration and invasiveness but regulated cell cycle progression, and promoted cell adhesion of Fadu and Cal27 cells. Additionally, high CCDC60 expression had strong connections with the infiltrating levels of immune cells, immune marker sets, immunomodulators and chemokines in HNSC, suggesting that targeting CCDC60 could be a promising strategy to enhance the efficacy of immunotherapy for HNSC patients. Conclusion: Tumor suppressor CCDC60 may be identified as a prognostic and immune-related indicator in HNSC, which had the potential functions in regulating the immune infiltration of HNSC and improving the response to immunotherapy for HNSC patients. [ABSTRACT FROM AUTHOR]

Background: Competitive Endogenous RNA (ceRNA) may be closely associated with tumor progression. However, studies on ceRNAs and immune cells in LUAD are scarce.Method: The profiles of gene expression and clinical data of LUAD patients were extracted from the TCGA database. Bioinformatics methods were used to evaluate differentially-expressed genes (DEGs) and to form a ceRNA network. Preliminary verification of clinical specimens was utilized to detect the expressions of key biomarkers at the tissues. Cox and Lasso regressions were used to identify key genes, and prognosis prediction nomograms were formed. The mRNA levels of 9 genes in the risk score model in independent clinical LUAD samples were detected by qRT-PCR. The interconnection between the risk of cancer and immune cells was evaluated using the CIBERSORT algorithm, while the conformation of notable tumor-infiltrating immune cells (TIICs) in the LUAD tissues of the high and low risk groups was assessed using the RNA transcript subgroup in order to identify tissue types. Finally, co-expression study was used to examine the interconnection between the key genes in the ceRNA networks and the immune cells.Result: A ceRNA network of 115 RNAs was established, and nine key genes were identified to construct a Cox proportional-hazard model and create a prognostic nomogram. This risk-assessment model might serve as an independent factor to forecast the prognosis of LUAD, and it was consistent with the preliminary verification of clinical specimens. Survival analysis of clinical samples further validated the potential value of high risk groups in predicting LUAD prognosis. Five immune cells were identified with significant differences in the LUAD tissues of the high and low risk groups. Besides, two pairs of biomarkers associated with the growth of LUAD were found, i.e., E2F7 and macrophage M1 (R = 0.419, p = 1.4e- 08) and DBF4 and macrophage M1 (R = 0.282, p < 2.2 e- 16).Conclusion: This study identified several important ceRNAs, i.e. (E2F7 and BNF4) and TIICs (macrophage M1), which might be related to the development and prognosis of LUAD. The established risk-assessment model might be a potential tool in predicting LUAD of prognosis. [ABSTRACT FROM AUTHOR]

Growing evidence has illustrated critical roles of competing endogenous RNA (ceRNA) regulatory network in human cancers including hepatocellular carcinoma. In this study, we aimed to find promising diagnostic and prognostic biomarkers for patients with hepatocellular carcinoma. Three novel unfavorable prognosis-associated genes (CELSR3, GPSM2, and CHEK1) was first identified. We also demonstrated that these genes were significantly upregulated in hepatocellular carcinoma cell lines and tissues. Next, 154 potential miRNAs of CELSR3, GPSM2, and CHEK1 were predicted. CHEK1-hsa-mir-195-5p/hsa-mir-497-5p and GPSM2-hsa-mir-122-5p axes were defined as two key pathways in carcinogenesis of hepatocellular carcinoma by combination of in silico analysis and experimental validation. Subsequently, lncRNAs binding to hsa-mir-195-5p, hsa-mir-497-5p, and hsa-mir-122-5p were predicted via starBase and miRNet databases. After performing expression analysis and survival analysis for these predicted lncRNAs, we showed that nine lncRNAs (SNHG1, SNHG12, LINC00511, HCG18, FGD5-AS1, CERS6-AS1, NUTM2A-AS1, SNHG16, and ASB16-AS1) were markedly increased in hepatocellular carcinoma and their upregulation indicated poor prognosis. Moreover, a similar mRNA-miRNA-lncRNA analysis for six "known" genes (CLEC3B, DNASE1L3, PTTG1, KIF2C, XPO5, and UBE2S) was performed. Subsequently, a comprehensive mRNA-miRNA-lncRNA triple ceRNA network linked to prognosis of patients with hepatocellular carcinoma was established. Moreover, all RNAs in this network exhibited significantly diagnostic values for patients with hepatocellular carcinoma. In summary, the current study constructed a mRNA-miRNA-lncRNA ceRNA network associated with diagnosis and prognosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Copy number variation ( CNV) has been reported to be associated with chemotherapy response, which affects disease prognosis. Here, we determined the frequency of genome-wide cytogenetic CNV aberrations in Korean patients with normal karyotype ( NK) acute myeloid leukaemia ( AML) and tested whether these genomic variations contribute to differences in Ara- C and anthracycline-based chemotherapy responses. Bone marrow aspirates and blood from 30 previously untreated de novo NK- AML patients were provided at the time of diagnosis for copy number analysis. Possible associations between cytogenetic aberrations and clinical parameters were analysed. CNVs were identified in 23 (76.7%) of the 30 cases tested. Multivariate analyses controlled for other clinical co-variates showed that patients having copy number loss had a decreased probability of complete remission ( OR, 0.015 [95% CI, 0-0.737], p = 0.035). Patients who had a copy number gain of more than four regions tended to have shorter event-free survival ( EFS) ( p = 0.083) with multivariate analysis showing that CNV increase is an independent predictive factor for shorter EFS ( HR, 22.104 [95% CI, 1.644-297.157], p = 0.020). In addition, we identified candidate genes that may be involved in Ara- C and anthracycline drug response in Korean patients with NK- AML. These results suggest that CNVs may affect the success of Ara- C and anthracycline-based chemotherapy in Korean patients with NK- AML. [ABSTRACT FROM AUTHOR]