Prognostic Value of Long Non-Coding RNA HULC and MALAT1 Following the Curative Resection of Hepatocellular Carcinoma.
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ABSTRACT:
SUBMITTER: Sonohara F
PROVIDER: S-EPMC5700934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection.A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria.Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775-0.799) and 0.714 (95%CI 0.695-0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA.The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection.
| S-EPMC5369882 | biostudies-literature
Project description:BackgroundThe prognosis of hepatocellular carcinoma (HCC) is not optimistic. Our study focused on present inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-lymphocyte ratio (ALR) and fibrinogen-to-albumin ratio (FAR), and explored their optimal combination for the prognosis of HCC after resection.MethodsA total of 347 HCC patients who underwent curative resection were enrolled. The optimal cutoff values of the inflammatory markers were calculated using receiver operating characteristic (ROC) curve analysis, and used to divide patients into two groups whose differences were compared by Kaplan-Meier analysis. Cox univariate and multivariate analyses were used to analyze the independent prognostic inflammatory markers. The χ2 test was chosen to determine the relationship between independent prognostic inflammatory markers and clinicopathological features. We created combined scoring models and evaluated them by Cox univariate and multivariate methods. The concordance index (C-index), Akaike information criterion (AIC) and likelihood ratio were calculated to compare the models. The selected optimal inflammatory markers and their combinations were tested in different stages of HCC by Kaplan-Meier analysis.ResultsThe ALR and GPR were independent prognostic factors for disease-free survival (DFS); the ALR, PLR, and GPR were independent prognostic factors for overall survival (OS). The proposed GPR and ALR-GPR-PLR score models were independent predictors for DFS and OS, respectively.ConclusionThe preoperative GPR and ALR-GPR-PLR score models were independent predictors for DFS and OS, respectively, and performed well in stratifying patients with HCC. The higher the score in the model was, the worse the prognosis.
| S-EPMC8447627 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide; however, accurate prognostic tools are still lacking. We aimed to identify immunohistochemistry (IHC)-based signature as a prognostic classifier to predict recurrence and survival in patients with HCC at Barcelona Clinic Liver Cancer (BCLC) early- and immediate-stage. In total, 567 patients who underwent curative liver resection at two independent centers were enrolled. The least absolute shrinkage and selection operator regression model was used to identify significant IHC features, and penalized Cox regression was used to further narrow down the features in the training cohort (n = 201). The candidate IHC features were validated in internal (n = 101) and external validation cohorts (n = 265). Three IHC features, hepatocyte paraffin antigen 1, CD34, and Ki-67, were identified as candidate predictors for recurrence-free survival (RFS), and were used to categorize patients into low- and high-risk recurrence groups in the training cohort (P < 0.001). The discriminative performance of the 3-IHC_based classifier was validated using internal and external cohorts (P < 0.001). Furthermore, we developed a 3-IHC_based nomogram integrating the BCLC stage, microvascular invasion, and 3-IHC_based classifier to predict 2- and 5-year RFS in the training cohort; this nomogram exhibited acceptable area under the curve values for the training, internal validation, and external validation cohorts (2-year: 0.817, 0.787, and 0.810; 5-year: 0.726, 0.662, and 0.715; respectively). The newly developed 3-IHC_based classifier can effectively predict recurrence and survival in patients with early- and intermediate-stage HCC after curative liver resection.
| S-EPMC7874098 | biostudies-literature
Project description:BackgroundMultiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients' prognosis.MethodsA total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People's Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients' survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM).ResultsPatients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40-2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39-2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716-0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25-2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20-2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses.ConclusionIn a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.
| S-EPMC8505987 | biostudies-literature
Project description:PurposePlatelet derived growth factor-BB (PDGF-BB) has emerged as one of the key cytokines in malignant transformation of different cells. PDGF-BB also exhibits a potent mitogenic effect on liver cells; studies have advocated clinical implications of monitoring serum PDGF-BB (sPDGF-BB) in patients with liver disease. We thus investigated the predictive relevance of perioperative sPDGF-BB after curative resection of hepatocellular carcinoma (HCC).MethodsWe evaluated perioperative sPDGF-BB in a prospective homogenous cohort of 40 patients diagnosed with HCC. During the first two-year follow-up, patients were evaluated every three months for postresection HCC recurrence.ResultsPatients who developed recurrence during two-year follow-up were found to have lower concentration of sPDGF-BB than those without recurrence in both pre- and postoperative settings (P < 0.05 and P < 0.001, resp.). We validated that the reduced postoperative sPDGF-BB (< 2133.29 pg/mL) was associated with an increased incidence of postresection HCC recurrence [area under curve (AUC) > 0.8, 95% confidence interval (CI) = 0.68 - 0.94, P < 0.001]; furthermore, we were able to demonstrate that postoperative sPDGF-BB was an independent predictor of HCC recurrence (hazard ratio = 5.64, 95% CI = 1.56 - 20.30, P < 0.01).ConclusionsThese findings provide a new insight into an association between diminished perioperative sPDGF-BB and HCC recurrence. Patients with low perioperative sPDGF-BB progressed early HCC recurrence. Therefore, evaluating perioperative sPDGF-BB may provide useful clinical information to characterize patients with postresection HCC recurrence.
| S-EPMC6339767 | biostudies-literature
Project description:BackgroundMolecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker.MethodsWe analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection.ResultsGPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences.ConclusionsDownregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.
| S-EPMC5580443 | biostudies-literature
Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC.MethodsWe used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA.ResultsAmong the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001).ConclusionsOur findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.
| S-EPMC4931379 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have been identified as playing critical roles in multiple diseases. However, little is known regarding their roles and mechanisms in post-stroke angiogenesis. Our studies focused on deciphering the functional roles and the underlying mechanisms of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the process of angiogenesis following oxygen-glucose deprivation/reoxygenation (OGD/R). We characterized the up-regulation of MALAT1 expression in the process of angiogenesis after hypoxic injury in vivo and in vitro. We further showed that compared with the empty vector, MALAT1 knockdown had significantly reduced the capacity for angiogenesis, which was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), scratching, cell cycle and immunofluorescent staining. Thus, our findings suggest that MALAT1 may mediate proangiogenic function in OGD/R. To further explore the potential mechanisms, we used lentiviruses expressing shMALAT1 and empty vector; the results revealed that shMALAT1 reduced the expression of 15-lipoxygenase 1 (15-LOX1), vascular endothelial growth factor (VEGF) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). Taken together, our results are the first to propose that MALAT1 may regulate angiogenesis through the 15-LOX1/STAT3 signalling pathway, and they may provide a critical target for the treatment of hypoxic injury and an avenue for therapeutic angiogenesis.
| S-EPMC6433728 | biostudies-literature
Project description:Downregulation of MicroRNA-122 (miR-122) and its association with cancer progression have been reported in hepatocellular carcinoma (HCC) cell line models and a limited number of HCC samples. Recently, restoration of miR-122 expression by direct delivery of miR-122 yielded promising results in HCCs. However, the prognostic effect of miR-122 expression in human HCC samples is not fully understood. We investigated the expression level of miR-122 by quantitative real-time polymerase chain reaction in 289 curatively resected HCC samples and 20 normal liver samples and evaluated the prognostic effect of miR-122 expression. The relative quantification value of miR-122 was much lower in HCC samples than in normal liver tissues. During a median 119 months of follow-up for survival, the low miR-122 expression group showed shorter recurrence-free survival (RFS) (p = 0.033) and intrahepatic recurrence-free survival (IHRFS) (p = 0.014), and a trend of short distant metastasis-free survival (DMFS) (p = 0.149) than high expression group. On multivariate analysis, miR-122 expression was an independent prognostic factor for RFS, IHRFS and DMFS. Downregulation of miR-122 expression, frequently found in HCC samples, was an independent prognostic factor for RFS after curative resection. Emerging therapeutic approaches targeting miR-122 could be applicable in patients with miR-122 downregulated hepatocellular carcinoma.
| S-EPMC6791887 | biostudies-literature
Project description:Purpose:This study aimed to explore serum lipoprotein (a) (Lp(a)) levels and investigate their prognostic value in hepatocellular carcinoma (HCC) patients after curative resection. Materials and methods:One cohort of 102 healthy individuals, one cohort of 172 HCC patients, and one cohort of 171 HCC patients undergoing curative resection were studied to evaluate serum Lp(a) levels and their prognostic significance, using Kaplan-Meier curves and log-rank tests. Results:The Lp(a) levels in HCC patients were significantly lower than those in healthy individuals. Furthermore, the levels in HCC patients were significantly associated with recurrence. HCC patients were stratified into high Lp(a) (>20 mg/L) and low Lp(a) (?20 mg/L) groups, using an optimal cutoff point for the Lp(a) of 20 mg/L. Low Lp(a) levels significantly correlated with tumor recurrence and survival time; HCC patients with low Lp(a) levels had higher recurrence rates and shorter survival time than those with high Lp(a) levels; Lp(a) was an independent prognostic factor for relapse-free survival and overall survival, and retained its prognostic value for ?-fetoprotein ?400 ng/mL and tumor size ?5 cm subgroups in the training and validation cohorts. Conclusion:Lp(a) was a promising and useful marker for assessing and monitoring recurrence and prognosis of patients with HCC, and improving Lp(a) levels may be a promising therapeutic strategy in HCC patients.
| S-EPMC6149830 | biostudies-other