scholarly journals Downregulation of snoRNA SNORA52 and Its Clinical Significance in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yuan Ding ◽  
Zhongquan Sun ◽  
Sitong Zhang ◽  
Yanjie Li ◽  
Xin Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Independent Prognostic Factor ◽  
Cox Regression Analysis ◽  
Overwhelming Evidence ◽  
Differentiation Degree ◽  
Nucleolar Rna

Hepatocellular carcinoma (HCC) is one of the most common and aggressive tumors in the world while the accuracy of the present tests for detecting HCC is poor. A novel diagnostic and prognostic biomarker for HCC is urgently needed. Overwhelming evidence has demonstrated the regulatory roles of small nucleolar RNA (snoRNA) in carcinogenesis. This study is aimed at analyzing the expression of a snoRNA, SNORA52, in HCC and exploring the correlation between its expression and various clinical characteristics of HCC patients. By using quantitative real-time PCR, we found that SNORA52 was downregulated in HCC cell lines ( P < 0.05 ) and HCC tissues ( P < 0.001 ). Correlation analysis showed that the expression of SNORA52 was obviously associated with tumor size ( P = 0.011 ), lesion number ( P = 0.007 ), capsular invasion ( P = 0.011 ), tumor differentiation degree ( P = 0.046 ), and TNM stage ( P = 0.004 ). The disease-free survival (DFS) and overall survival (OS) analysis showed that patients with lower SNORA52 expression had a worse prognosis ( P < 0.001 ). Univariate and multivariate Cox regression analysis showed that SNORA52 expression was a completely independent prognostic factor to predict DFS ( P = 0.009 ) and OS ( P = 0.012 ) of HCC patients. Overall, our findings showed SNORA52 expression levels were downregulated in HCC tissues and correlated with multiple clinical variables, and SNORA52 was an independent prognostic factor for HCC patients, which suggested that SNORA52 could function as a potential diagnostic and prognostic biomarker for HCC patients.

scholarly journals Expression of EEF1A1 Is Associated with Prognosis of Patients with Colon Adenocarcinoma

2019 ◽  
Vol 8 (11) ◽  
pp. 1903 ◽  
Author(s):  
Eun kyo Joung ◽  
Jiyoung Kim ◽  
Nara Yoon ◽  
Lee-so Maeng ◽  
Ji Hoon Kim ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Colon Adenocarcinoma ◽  
Independent Prognostic Factor ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Disease Free

Background: The prognostic role of the translational factor, elongation factor-1 alpha 1 (EEF1A1), in colon cancer is unclear. Objectives: The present study aimed to investigate the expression of EEF1A in tissues obtained from patients with stage II and III colon cancer and analyze its association with patient prognosis. Methods: A total of 281 patients with colon cancer who underwent curative resection were analyzed according to EEF1A1 expression. Results: The five-year overall survival in the high-EEF1A1 group was 87.7%, whereas it was 65.6% in the low-EEF1A1 expression group (hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.38–4.44, p = 0.002). The five-year disease-free survival of patients with high EEF1A1 expression was 82.5%, which was longer than the rate of 55.4% observed for patients with low EEF1A1 expression (HR 2.94, 95% CI 1.72–5.04, p < 0.001). Univariate Cox regression analysis indicated that age, preoperative carcinoembryonic antigen level, adjuvant treatment, total number of metastatic lymph nodes, and EEF1A1 expression level were significant prognostic factors for death. In multivariate analysis, expression of EEF1A1 was an independent prognostic factor associated with death (HR 3.01, 95% CI 1.636–5.543, p < 0.001). EEF1A1 expression was also an independent prognostic factor for disease-free survival in multivariate analysis (HR 2.54, 95% CI 1.459–4.434, p < 0.001). Conclusions: Our study demonstrated that high expression of EEF1A1 has a favorable prognostic effect on patients with colon adenocarcinoma.

scholarly journals Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion

2021 ◽  
Vol 27 ◽  
Author(s):  
Ruohao Zhang ◽  
Miao Huang ◽  
Hong Wang ◽  
Shengming Wu ◽  
Jiali Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Comparative Genomic ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Cox Regression Analysis ◽  
Potential Biomarkers

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC.Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis.Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion.Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.

Correlation of loss of spinophilin expression with increased proliferation and viability as a prognostic factor in patients with hepatocellular carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15064-e15064
Author(s):  
Anna Lena Ress ◽  
Ariane Aigelsreiter ◽  
Silvia Schauer ◽  
Florian Eisner ◽  
Hellmut Samonigg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Number Of Patients ◽  
Mib 1

e15064 Background: A loss of the putative tumorsuppressor protein spinophilin has been recently involved in the pathogenesis of lung and other carcinoma types. However, a detailed study of the clinical significance and functional cellular effects of spinophilin in hepatocellular carcinoma (HCC) has never been performed. Methods: In this study, we determined for the first time the expression pattern of spinophilin and some of it´s known interacting/down-stream genes (p53, p14ARF, pRB) and proliferation markers (MIB-1 and Cyclin D) in human hepatocellular carcinoma (HCC). The prognostic relevance of spinophilin expression was determined on a cohort of 104 HCC patients who underwent primary tumor resection, followed by functional gene silencing studies. Results: Reduced spinophilin expression was detected by three independent methods (Western blot, RT-PCR and IHC) in a substantial number of patients (70%, p<0.05). Loss of spinophilin expression in HCC tissue was correlated with increased MIB-1 proliferation marker (p=0.01). In terms of clinical outcome, the disease-free survival (DFS) rate was 14.8% and 39.1% (p=0.010) and the cancer-specific survival (CSS) rate was 23.5% and 43.5% (p=0.006) for patients with low and high spinophilin expression, respectively. Multivariate Cox regression analysis identified low expression of spinophilin as an independent poor prognostic factor with respect to DFS (HR=1.8, CI=1.04-3.40, p=0.043) and CSS (HR=2.0, CI=1.1-3.8, p=0.025). Silencing of spinophilin expression in HepG2 cells was associated with increased cellular growth rate (p<0.05). Conclusions: According to our data, the loss of this putative tumor suppressor protein is an independent negative prognosticator for the clinical outcome of HCC patients. Reduced levels of spinophilin expression are associated with higher proliferation rates of HCC cells.

scholarly journals Connection Between EIF3S3 Polymorphisms and Hepatocellular Carcinoma Prognosis

2020 ◽  
Author(s):  
Chao Yang ◽  
Peng Du ◽  
Wei Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Initiation Factor ◽  
Mrna Levels ◽  
Clinical Role ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Background: EIF3S3 that encodes a p40 subunit of eukaryotic initiation factor 3 (eIF3), has been reported overexpression in several human malignancies. The expression of EIF3S3 in hepatocellular carcinoma (HCC) and its clinical role in the disease progression is still unclear. Here we aimed to study the effect of EIF3S3 on HCC prognosis.Methods: Quantitative real-time polymerase chain-reaction (qRT-PCR) was performed to assess the mRNA levels of EIF3S3 in 120 HCC tissues samples and 60 adjacent noncancerous specimens. Kaplan-Meier and Cox regression analysis was used to study the prognostic value of EIF3S3.Results: The expression of EIF3S3 was significantly increased in HCC compared to the expression found in adjacent tissues (P<0.001). Furthermore, high EIF3S3 expression was positively correlated with vascular invasion, tumor size, cirrhosis, AFP levels and TNM stage (all P<0.05). Kaplan-Meier survival analysis showed that patients with high EIF3S3 expression had worse overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) than those with low EIF3S3 expression. In addition, multivariable analysis revealed that EIF3S3 could be an independent prognostic factor of OS (P<0.001) and DFS (P<0.001) for patients with HCC.Conclusion: The results suggested that EIF3S3 might serve as a promising prognostic factor for OS and DFS of HCC patients.

scholarly journals The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

2021 ◽  
Author(s):  
Philip J. Johnson ◽  
Sofi Dhanaraj ◽  
Sarah Berhane ◽  
Laura Bonnett ◽  
Yuk Ting Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Models ◽  
Controlled Study ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

2021 ◽  
Author(s):  
Xinxin Chen ◽  
Wenxia Qiu ◽  
Xuekun Xie ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Tumor Diameter ◽  
Cox Regression Analysis ◽  
Tumor Capsule ◽  
Calibration Curves ◽  
Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

scholarly journals Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer

2019 ◽  
Vol 8 (10) ◽  
pp. 1647 ◽  
Author(s):  
Sachiyo Onishi ◽  
Masahiro Tajika ◽  
Tsutomu Tanaka ◽  
Yutaka Hirayama ◽  
Kazuo Hara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Japanese Patients ◽  
Independent Prognostic Factor ◽  
Cancer Center ◽  
Advanced Esophageal Cancer ◽  
Cox Regression Analysis ◽  
Group 2

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.

Coexpression of PDGFR-Alpha, PDGFR-Beta and VEGF as a Prognostic Factor in Patients with Hepatocellular Carcinoma

2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Cox Regression Analysis

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

scholarly journals Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Peng Liu ◽  
Jinhong Wei ◽  
Feiyu Mao ◽  
Zechang Xin ◽  
Heng Duan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endoplasmic Reticulum ◽  
Regression Analysis ◽  
Endoplasmic Reticulum Stress ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Cancer Genome ◽  
Survival Prediction ◽  
Training Cohort ◽  
Cox Regression Analysis

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.

scholarly journals The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer

2020 ◽  
Vol 27 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Xinyue Wang ◽  
Xiwen Bi ◽  
Zhangzan Huang ◽  
Jiajia Huang ◽  
Wen Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Metastatic Breast Cancer ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Independent Prognostic Factor ◽  
First Line ◽  
Cox Regression Analysis

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.

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