scholarly journals Clusterin role in hepatocellular carcinoma patients treated with oxaliplatin

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Xiumei Wang ◽  
Yongqiang Liu ◽  
Qiong Qin ◽  
Ti Zheng

Abstract Aim: To explore the prognostic value of clusterin (CLU) in hepatocellular carcinoma (HCC) patients treated with oxaliplatin (OXA). Methods: Relative expression of plasma CLU mRNA was examined via fluorescence quantitative real-time PCR (qRT-PCR), and CLU protein level in tissue samples was detected through immunohistochemistry. Chi-square test was used to analyze the relationship between CLU mRNA expression and clinical features of HCC patients treated with OXA. Kaplan–Meier method was performed to assess overall survival for the patients, and prognostic value of CLU in HCC patients was estimated via Cox regression analysis. Results: CLU expression in plasma and tissue specimens was significantly higher among HCC patients than in non-malignant controls (P < 0.001 for both). Moreover, elevated CLU mRNA was closely related to tumor stage, lymph node metastasis and response to OXA (P < 0.05). HCC patients with high CLU expression showed poor response to OXA. In addition, low CLU levels predicted long overall survival time among the study subjects (20.8 vs. 36.6 months, P < 0.001). CLU was an independent prognostic indicator for HCC patients treated with OXA (HR = 2.587, 95%CI = 1.749–3.828, P < 0.001). Conclusion: CLU may be a novel prognostic marker for HCC patients treated with OXA.

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Kidane Siele Embaye ◽  
Qing Yang ◽  
Lingzhi Qin ◽  
Chao Zhang ◽  
...  

Abstract Background: Given that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes(MRGs) for hepatocellular carcinoma (HCC) diagnosis and treatment. Methods: The metabolism-related genes sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium(ICGC) and The Cancer Genome Atlas (TCGA). The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate Cox regression analysis were performed to identify metabolism-related DEGs that related to overall survival(OS). A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses . Furthermore, the signature was validated in the TCGA dataset. Finally, cox regression analysis was applied to identify the prognostic value and clinical relationship of the signature in HCC. Results: A total of 178 differentially expressed MRGs were detected between the ICGA dataset and the TCGA dataset. We found that 17 MRGs were most significantly associated with OS by using the univariate Cox proportional hazards regression analysis in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes, and were further associated with tumor TNM stage, gender, age, and pathological stage. Finally, the signature was found to be associated with various clinicopathological features. Conclusions: In summary, our data provided evidence that the metabolism-based signature could serve as a reliable prognostic and predictive tool for overall survival in patients with HCC.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Manni Wang ◽  
Hui Xu ◽  
Liu Xiao ◽  
Wenpeng Song ◽  
Sha Zhu ◽  
...  

Objectives. The aim of this study is to explore the textural features that may identify the morphological changes in the lymphoma region and predict the prognosis of patients with primary renal lymphoma (PRL) and primary adrenal lymphoma (PAL). Methods. This retrospective study comprised nineteen non-Hodgkin’s lymphoma (NHL) patients undergoing 18F-FDG-PET/CT at West China Hospital from December 2013 to May 2017. 18F-FDG-PET images were reviewed independently by two board certificated radiologists of nuclear medicine, and the texture features were extracted from LifeX packages. The prognostic value of PET FDG-uptake parameters, patients’ baseline characteristics, and textural parameters were analyzed using Kaplan–Meier analysis. Cox regression analysis was used to identify the independent prognostic factors among the imaging and clinical features. Results. The overall survival of included patients was 18.84 ± 13.40 (mean ± SD) months. Univariate Cox analyses found that the tumor stage, GLCM (gray-level co-occurrence matrix) entropy, GLZLM_GLNU (gray-level nonuniformity), and GLZLM_ZLNU (zone length nonuniformity), values were significant predictors for OS. Among them, GLRLM_RLNU ≥216.6 demonstrated association with worse OS at multivariate analysis (HR 9.016, 95% CI 1.041–78.112, p=0.046). Conclusions. The texture analysis of 18F-FDG-PET images could potentially serve as a noninvasive strategy to predict the overall survival of patients with PRL and PAL.


2020 ◽  
Author(s):  
Zhong Dai ◽  
Ke-Qing Yao ◽  
Xing-Sheng Hu ◽  
Yi-Qun Li ◽  
Yu-Tao Liu ◽  
...  

Abstract Background: Rab25 was indicated to be involved in several human tumors. However, the clinical significance of Rab25 in hepatocellular carcinoma (HCC) was still unclear. The purpose of this study was to investigate the expression and prognostic value of Rab25 in HCC.Methods: The relative mRNA expression levels of Rab25 in HCC tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the relationship between Rab25 expression and clinical characteristics of patients. The prognostic value of Rab25 in HCC was estimated through Kaplan-Meier method and cox regression analysis.Results: Rab25 gene expression level was significantly higher in HCC tissues than that in normal tissues (P<0.001). Importantly, the increased Rab25 expression was closely associated with TNM stage (P=0.024), metastasis (P=0.022) and invasion classification (P=0.039). Moreover, patients with high Rab25 expression tended to have obviously shorter overall survival than those with low expression of Rab25 (log rank test, P<0.001) via Kaplan-Meier analysis. Univariate and multivariate cox regression analyses revealed that Rab25 was an independent prognostic factor of HCC.Conclusions: Rab25 is up-regulated in HCC and contributes to the progression of this tumor. What’s more, Rab25 may be a potential bio-marker for the prognosis of HCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Feiyu Mao ◽  
Duguang Li ◽  
Zechang Xin ◽  
Yan Du ◽  
Xiaodong Wang ◽  
...  

COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis ( p < 0.0001 ), TNM clinical stage ( p < 0.0001 ), and pathology differentiation ( p < 0.01 ). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival ( p < 0.001 ) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients’ overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.


2020 ◽  
Author(s):  
Ran Wei ◽  
Jichuan Quan ◽  
Shuofeng Li ◽  
Zhao Lu ◽  
Xu Guan ◽  
...  

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11273
Author(s):  
Lei Yang ◽  
Weilong Yin ◽  
Xuechen Liu ◽  
Fangcun Li ◽  
Li Ma ◽  
...  

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.


2021 ◽  
Author(s):  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
I-Cheng Lu ◽  
...  

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


2021 ◽  
Vol 20 ◽  
pp. 153303382110414
Author(s):  
Xiaoyong Li ◽  
Jiaqong Lin ◽  
Yuguo pan ◽  
Peng Cui ◽  
Jintang Xia

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Zheng Yao ◽  
Song Wen ◽  
Jun Luo ◽  
Weiyuan Hao ◽  
Weiren Liang ◽  
...  

Background. Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. Methods. The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. Results. Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. Conclusions. The present study may contribute to the improvement of current prognostic systems for patients with HCC.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


Sign in / Sign up

Export Citation Format

Share Document