The Clinical Significance of RMI2 in Hepatocellular Carcinoma.
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ABSTRACT:
SUBMITTER: Zheng Ms B
PROVIDER: S-EPMC8516379 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.
| S-EPMC6235894 | biostudies-literature
Project description:NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.
| S-EPMC11321415 | biostudies-literature
Project description:To study the clinical significance of HINT2 expression in patients with HCC.We investigated HINT2 mRNA expression in tumors and adjacent non-tumor hepatic tissues from 106 HCC patients using quantitative real-time PCR. Appropriate statistical methods were then applied to assess the relationships between the HINT2 mRNA level and clinical parameters.HINT2 was significantly down-regulated in HCC (P < .0001). No significant correlation was found between HINT2 expression and clinicopathological factors in HCC patients. A Kaplan-Meier survival curve showed that HINT2 expression is related to recurrence-free survival (P < .05). Multivariate analyses revealed that tumor size and HINT2 expression are risk factors for HCC recurrence.HINT2 is down-regulated in HCC, and low HINT2 expression predicts earlier tumor recurrence. HINT2 expression may serve as a prognostic indicator of recurrence in HCC.
| S-EPMC6890357 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-21 | GSE222853 | GEO
Project description:Lipopolysaccharide binding protein (LBP) has been reported to be associated with prognosis in colorectal carcinoma and renal cell carcinoma; however, the clinical significance of LBP in human primary hepatocellular carcinoma (HCC) is inconclusive. We aimed to investigate the clinical significance and prognostic value of LBP in human primary HCC. In the present study, 346 patients with HCC who underwent curative resection were retrospectively analyzed. LBP protein expression was evaluated using western blot analysis and immunohistochemistry. LBP scores collected from immunohistochemical analysis were obtained by multiplying staining intensity and the percentage of positive cells. An outcome-based best cutoff-point was calculated by X-tile software. Moreover, Kaplan-Meier curves and Cox regressions were used for prognosis evaluation. LBP was frequently overexpressed in HCC compared with that in peritumor tissues (five pairs by western blot analysis, P=0.0533; 77 pairs by immunohistochemistry, P=0.0171), and LBP expression was positively associated with tumor-node-metastasis stage and tumor differentiation. Patients who had high LBP expression had decreased overall survival and time to recurrence compared with patients with low LBP expression. Furthermore, patients who were both serum α-fetoprotein positive and had high LBP expression had poor prognoses. Univariate and multivariate Cox analyses indicated that this combination was an independent prognostic factor [overall survival: Hazard ratio (HR), 1.458; 95% confidence interval (CI), 1.158-1.837; P=0.001; time to recurrence: HR,1.382; 95% Cl, 1.124-1.700; P=0.002]. In conclusion, LBP is highly expressed in HCC, and high LBP expression combined with serum α-fetoprotein may predict poor outcomes in patients with HCC following curative resection.
| S-EPMC6924111 | biostudies-literature
Project description:PurposeRibosomal protein metallopanstimulin-1 (MPS-1) is implicated in tumorigenesis. However, to date, the underlying role of MPS-1 in the generation, progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. This study aims to investigate the expression of MPS-1 in HCC and its significance for the prognosis of HCC.MethodsThe Oncomine and GEPIA databases were used to analyze the expression pattern of MPS-1 in HCC. Immunohistochemical staining was performed on tissue microarrays containing 169 HCC tissue samples to examine the expression of MPS-1. In addition, univariate and multivariate Cox regression analyses and Kaplan-Meier analysis were used to verify the correlation between clinicopathological factors in HCC patients and its clinical prognostic significance.ResultsMPS-1 was more highly expressed in HCC than in normal tissues, and MPS-1 expression was correlated with serum AFP levels (P = 0.003), liver cirrhosis (P = 0.024), tumor embolus (P = 0.009) and tumor recurrence (P < 0.003). MPS-1 was an independent prognostic factor for the overall survival of HCC (HR, 1.92; 95% CI, 1.01-3.68), and a higher expression of MPS-1 predicted poorer survival. Furthermore, high expression of MPS-1 indicated a poor prognosis in patients with AFP positivity, cirrhosis or HBsAg positivity.ConclusionThese findings demonstrate that MPS-1 is highly expressed in HCC and serves as an independent prognostic marker, highlighting the potential role of MPS-1 as a novel biomarker and therapeutic target for HCC.
| S-EPMC8647167 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.
| S-EPMC8255377 | biostudies-literature
Project description:Telomerase reactivation during hepatocarcinogenesis is recurrently caused by two point mutations occurring most frequently at the nucleotide -124 (95%) and occasionally at the nucleotide -146 (<5%) upstream of the TERT translational start site in hepatocellular carcinoma (HCC). In this study, we designed a droplet digital PCR (ddPCR) assay to detect TERT promoter (TERTp) nucleotide change G>A at position -124 and to quantify the mutant allele frequency (MAF) in 121 primary liver cancers, including 114 HCC along with 23 autologous cirrhotic tissues, five cholangiocarcinoma (CC), and two hepato-cholangiocarcinoma (HCC-CC). All cases were evaluated for tumour markers such as α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). We compared the sensitivity of ddPCR and Sanger sequencing and investigated the prognostic relevance of TERTp mutations. The TERTp G>A transition was identified in 63.6% and 52.1% of HCC samples by ddPCR and Sanger sequencing, respectively. One out of 23 (4.3%) peri-tumour tissues tested positive only by ddPCR. One out of five CC (20%) and none of the HCC-CC were found concordantly mutated by the two methods. The TERTp MAF ranged from 2% to 66%, and the large majority (85.5%) of mutated samples showed a value above 20%. A statistically significant correlation was found between TERTp mutation and tumour size (p = 0.048), while an inverse correlation was observed with CA19-9 levels (p = 0.0105). Moreover, HCC patients with TERTp -124A had reduced survival. In conclusion, the single nucleotide variation G>A at position -124 in TERTp, detected either by ddPCR or by Sanger sequencing, showed a remarkable high frequency in HCC. Such mutation is associated with lower levels of CA19-9 and reduced survival in HCC patients suggesting that the TERTp status may represent a distinct signature of liver cancer subgroups.
| S-EPMC8345216 | biostudies-literature
Project description:BackgroundTherapies targeting immune molecules have rapidly been adopted and advanced the treatment of hepatocellular carcinoma (HCC). Nonetheless, no studies have reported a systematic analysis between immunological profiles and clinical significance in HCC.MethodsWe comprehensively investigated immune patterns and systematically correlated 22 types of both adaptive and innate immune cells with genomic characteristics and clinical outcomes based on 370 HCC patients from The Cancer Genome Atlas (TCGA) database through a metagene approach (known as CIBERSORT). Based on the Quantitative Pathology Imaging and Analysis System coupled with integrated high-dimensional bioinformatics analysis, we further independently validated six immune subsets (CD4+ T cells, CD8+ T cells, CD20+ B cells, CD14+ monocytes, CD56+ NK cells, and CD68+ macrophages), and shortlisted three (CD4+ T cells, CD8+ T cells, and CD56+ NK cells) of which to investigate their association with clinical outcomes in two independent Zhongshan cohorts of HCC patients (n = 258 and n = 178). Patient prognosis was further evaluated by Kaplan-Meier analysis and univariate and multivariate regression analysis.ResultsBy using the CIBERSORT method, the immunome landscape of HCC was constructed based on integrated transcriptomics analysis and multiplexed sequential immunohistochemistry. Further, the patients were categorized into four immune subgroups featured with distinct clinical outcomes. Strikingly, significant inter-tumoral and intra-tumoral immune heterogeneity was further identified according to the in-depth interrogation of the immune landscape.ConclusionThis work represents a potential useful resource for the immunoscore establishment for prognostic prediction in HCC patients.
| S-EPMC7862794 | biostudies-literature
Project description:Circular RNAs (circRNAs) constitute a class of non-coding RNAs recently discovered to be widespread and abundant in mammalian cells. However, the expression features of most of circRNAs in hepatocellular carcinoma (HCC) are unraveled. In this study, we focused on hsa_circ_0003570, which was found to be down-regulated in HCC tissues in our previous microarray screening. The hsa_circ_0003570 levels in HCC cell lines, HepG2, SMMC-7721, MHCC97L, MHCC97H, and HCCLM3, and human normal hepatic cell line L02 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, its levels in 107 paired HCC tissues and adjacent non-tumor tissues, 60 liver biopsy samples from patients with chronic liver diseases were detected by qRT-PCR. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of hsa_circ_0003570 for HCC. Hsa_circ_0003570 was not only first found down-regulated in HCC cell lines (P<.001) but also in HCC tissues (P<.001). Moreover, hsa_circ_0003570 was gradually decreased from chronic hepatitis (CH), to liver cirrhosis (LC) and to HCC tissues (P<.01). Its expression levels were significantly correlated with tumor diameter (P=.035), differentiation (P=.013), microvascular invasion (P=.045), Barcelona Clinic Liver Cancer stages (P=.011), tumor-node-metastasis stages (P=.016), and serum alpha-fetoprotein levels (P=.031). The ROC curve demonstrated that hsa_circ_0003570 had poor performance for differentiating HCC from LC and CH, but had relatively good performance for differentiating LC from CH. These results indicated that hsa_circ_0003570 expression levels were associated with HCC clinicopathological characteristics.
| S-EPMC6816847 | biostudies-literature