Unfavorable Predictor Of Overall Survival Research Articles

Circulating Extracellular Vesicle-Derived microRNAs as Novel Diagnostic and Prognostic Biomarkers for Non-Viral-Related Hepatocellular Carcinoma.

Extracellular vesicle-derived microRNAs (EV-miRNAs) are promising circulating biomarkers for chronic liver disease. In this study, we explored the potential significance of plasma EV-miRNAs in non-hepatitis B-, non-hepatitis C-related HCC (NBNC-HCC). We compared, using the NanoString method, plasma EV-miRNA profiles between NBNC-HCC and control groups including patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls. The differentially expressed EV-miRNAs were validated in another set of plasma samples by qRT-PCR. A total of 66 significantly differentially expressed EV-miRNAs between the HCC and the control groups were identified in the discovery set. In the validation cohort, including plasma samples of 70 NBNC-HCC patients, 70 NAFLD patients, and 35 healthy controls, 5 plasma EV-miRNAs were significantly elevated in HCC, which included miR-19-3p, miR-16-5p, miR-223-3p, miR-30d-5p, and miR-451a. These miRNAs were found to participate in several cancer-related signaling pathways based on bioinformatic analysis. Among them, EV-miR-19-3p exhibited the best diagnostic performance and displayed a high sensitivity for detecting alpha-fetoprotein-negative HCC and early-stage HCC. In multivariate analysis, a high EV-miR-19-3p level was demonstrated as an independently unfavorable predictor of overall survival in patients with NBNC-HCC. In conclusion, our data have indicated, for the first time, that EV-miR-19-3p could serve as a novel circulating biomarker for the diagnosis and prognosis of NBNC-HCC.

High pretreatment D-dimer level is an independent unfavorable prognostic factor of small cell lung cancer: A systematic review and meta-analysis.

Background:High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively.Methods:We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed.Results:A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I2 = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I2 = 0.0%) in patients with SCLC.Conclusion:High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.

Unambiguous advanced radiologic extranodal extension determined by MRI predicts worse outcomes in nasopharyngeal carcinoma: Potential improvement for future editions of N category systems

Background and purposeTo explore the prognostic value of different radiologic extranodal extension (rENE) grades and their potential improvement for the 8th edition N category in nasopharyngeal carcinoma (NPC). Materials and methodsFrom 2009 to 2013, a cohort of 1887 patients with NPC was retrospectively enrolled and randomized to the training (n = 955) and validation (n = 932) groups. rENE was categorized as follows: grade 0, nodes without rENE; grade 1, nodes with rENE infiltrating the surrounding fat only; grade 2, matted nodes; grade 3, nodes with rENE infiltrating adjacent structures. ResultsThe percentage of patients with MRI-positive cervical nodes was 66.5% (1254/1887), of whom grade 0, 1, 2 and 3 rENE cases accounted for 33.2% (416/1254), 14.9% (187/1254), 36.5% (458/1254) and 15.4% (193/1254), respectively. The kappa coefficients for the inter-rater and intra-rater assessments were 0.63, 0.51, 0.65 and 0.93, and 0.76, 0.69, 0.72 and 1.0 in grade 0, 1, 2 and 3 rENE, respectively. Grade 3 rENE rather than grades 0–2 rENE was an independent unfavorable predictor of overall survival and disease-free survival (P < 0.001). Recursive partitioning analysis was applied to refine the N category: eN0 (N0), eN1 (N1 without grade 3), eN2 (N2 without grade 3), and eN3 (N1/N2 with grade 3, N3). Compared to the current system, the proposed N category performed better in hazard consistency, hazard discrimination, sample size balance and outcome prediction. ConclusionGrade 3 rENE was an independent unfavorable indicator of NPC. Upstaging patients in N1-2 with grade 3 rENE to N3 led to a superior prognostic performance.

Downstream neighbor of SON (DONSON) is associated with unfavorable survival across diverse cancers with oncogenic properties in clear cell renal cell carcinoma.

A precise stratification of our patients is essential and can support clinicians to determine the right therapy. The aim of this study was to identify clinically relevant genes using The Cancer Genome Atlas (TCGA) datasets.A comprehensive pan-cancer analysis of 30 distinct tumor entities (N = 9022) identified the largely unknown gene Downstream neighbor of SON (DONSON) to be particularly associated with unfavorable overall survival in clear cell renal cell carcinoma (KIRC). This prognostic potential of DONSON was validated in an independent KIRC cohort via quantitative real-time PCR (n = 152). Further, DONSON protein expression was evaluated via immunohistochemical staining followed by quantitative image analysis using the image analysis software QuPath on a renal cancer tissue microarray (n = 270).Interestingly, DONSON overexpression was preferentially associated with poor survival in 9 of the 30 entities, suggesting tumor-independent oncogenic properties of this largely unknown gene. A particularly strong association of DONSON to an aggressive phenotype was evident in KIRC and proved to be a strong independent predictor of unfavorable overall survival in two additional cohorts on the mRNA and protein level. In our KIRC cell culture model, we observed a substantial attenuation of proliferative activity and migration capacity of the KIRC cells Caki1 and 769p.In conclusion, we identified DONSON as a robust biomarker for risk stratification in KIRC in three independent cohorts and provide evidence that DONSON is linked to a malignant phenotype in the KIRC cell culture model.

Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: A systematic review and meta-analysis.

Several studies have been conducted to evaluate the prognostic value of prothrombin induced by vitamin K absence-II (PIVKA-II) overexpression in hepatocellular carcinoma patients treated with curative ablation. However, the results remain controversial. The purpose of this meta-analysis was to explore the correlation between PIVKA-II expression and survival outcomes in these patients. We performed a systematic literature search in PubMed, EMBASE, Medline, Cochrane Library, and Web of Science to identify the relevant articles investigating the prognostic value of PIVKA-II in patients with hepatocellular carcinoma. Combined hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival and recurrence-free survival were calculated as the analysis endpoints. A total of 15 cohorts encompassing 5647 patients were included. The results indicated that elevated PIVKA-II was significantly associated with poorer overall survival (HR 1.59; 95% CI 1.40, 1.82; P < 0.001) and recurrence-free survival (HR 1.76; 95% CI 1.42, 2.17; P < 0.001). Similar results were observed in the subgroup analysis based on sample size, analytical method, treatment modality, and cut-off value. This meta-analysis suggests that elevated PIVKA-II is a predictor of unfavorable overall survival and recurrence-free survival in hepatocellular carcinoma patients receiving curative ablation. More rigorous studies are warranted to confirm the clinical utility of PIVKA-II in determining hepatocellular carcinoma prognosis.

Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies.

Background and aimsSeveral studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer.Materials and methodsEmbase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed.ResultsFifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17–1.40, P<0.00001; I2=42%). Similar results were observed in the subgroup analyses of OS, which was based on the analysis model, ethnicity, sample size and cut-off value. Further analyses based on the adjusted potential confounders were conducted, including CA199, neutrophil-to-lymphocyte ratio, modified Glasgow Prognostic Score, albumin, C-reactive protein, Eastern Cooperative Oncology Group, stage, tumor size, nodal involvement, tumor differentiation, margin status, age and gender, which confirmed that low PLR was a protective factor in pancreatic cancer. In addition, low PLR was significantly associated with longer PFS when compared to high PLR in pancreatic cancer (hazard ratio=1.27, 95% CI=1.03–1.57, P=0.03; I2=33%).ConclusionIn conclusion, it was found that high PLR is an unfavorable predictor of OS and PFS in patients with pancreatic cancer, and PLR is a promising prognostic biomarker for pancreatic cancer.

Prognostic role of long non-coding RNA TUG1 expression in various cancers: a meta-analysis.

Several studies were conducted to explore the prognostic role of long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) expression in various cancers, with contradictory. This study aims to summarize the prognostic role of lncRNA TUG1 expression in various cancers. Embase, PubMed and Cochrane Library were completely retrieved. The cohort studies focusing on the prognostic role of lncRNA TUG1 expression in various cancers were eligible. The endpoints were overall survival (OS) and clinicopathological parameters. 9 studies involving a total of 1,078 patients were identified. The results showed that high lncRNA TUG1 expression was obviously associated with worse OS when compared to the low lncRNA TUG1 expression (HR = 1.37, 95% CI = 1.07–1.76, P = 0.01; I2 = 85%). However, No distinct relationship was observed between the lncRNA TUG1 expression and age (OR = 0.99, 95% CI = 0.76–1.28, P = 0.92; I2 = 4%), gender (OR = 0.92, 95% CI = 0.70–1.22, P = 0.57; I2 = 0%), diameter (OR = 0.83, 95% CI = 0.34–2.01, P = 0.67; I2 = 85%), smoking (OR = 1.09, 95% CI = 0.37–3.21, P = 0.87; I2 = 73%), TNM stage (OR = 0.60, 95% CI = 0.25–1.43, P = 0.25; I2 = 86%) and lymph node metastasis (OR = 1.07, 95% CI = 0.47–2.45, P = 0.87; I2 = 86%). In conclusion, it was revealed that high lncRNA TUG1 expression is an unfavorable predictor of OS in patients with cancers, and lncRNA TUG1 expression is a promising prognostic biomarker for various cancers.

Prognostic role of platelet to lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis.

Background and AimsSeveral studies were conducted to explore the prognostic significance of platelet to lymphocyte ratio (PLR) in hepatocellular carcinoma (HCC), however, contradictory results across most reports were documented. To this end, we present a systematic review that aims to summarize the prognostic significance of PLR in patients with HCC.ResultsA total of 10 studies involving a total of 2,315 patients were identified. The Newcastle-Ottawa Quality Assessment Scale (NOS) of each included study was greater than or equal to 5. The results indicated that high PLR was significantly associated with a worse OS when compared to the low PLR (HR = 1.60, 95% CI = 1.23−2.08, p = 0.0005; I2 = 88%, p < 0.00001). Similar results were detected in the subgroup analysis of the analysis model, cut-off value, ethnicity, sample size and therapy. However, no obvious correlation between the PLR and DFS/RFS in patients with HCC was observed (HR = 1.21, 95% CI = 0.87−1.67, p = 0.26; I2 = 61%, p = 0.07).Materials and MethodsA complete literature search in the PubMed, Cochrane Library and Embase database was performed. Retrospective and prospective studies focusing on the role of PLR on the prognosis in HCC were all deemed as “suitable” for our scope. The endpoints determined were: the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and the progress free survival (PFS).ConclusionsThe study revealed that high PLR is an unfavorable predictor of OS in patients with HCC, and high PLR is a promising prognostic biomarker for HCC, especially for patients in Asia.

Prognostic role of podocalyxin-like protein expression in various cancers: A systematic review and meta-analysis.

Several studies were conducted to explore the prognostic significance of podocalyxin-like protein (PODXL) expression in various cancers, with contradictory. This study aims to summarize the prognostic significance of PODXL expression in cancers. PubMed, the Cochrane Library and Embase were completely retrieved. The prospective or retrospective studies focusing on the prognostic role of PODXL expression in cancers were eligible. The endpoints were overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS).12 studies involving a total of 5,309 patients were identified. The results indicated that high PODXL expression was significantly associated with worse OS when compared to the low PODXL expression (HR=1.76, 95%CI=1.53-2.04, p<0.00001; I2=41%, p=0.08). And similar results were detected in the subgroup analysis of analysis model, ethnicity, sample size, tumor type and antibody type. And the results also showed that high PODXL expression was obviously related to shorter DSS (HR=2.47, 95%CI=1.53-3.99, p=0.0002; I2=66%, p=0.03) and DFS (HR=2.12, 95%CI=1.58-2.85, p<0.00001; I2=19%, p=0.29). In conclusion, it was revealed that high PODXL expression is an unfavorable predictor of OS, DSS and DFS in patients with cancers, and high PODXL expression is a promising prognostic biomarker for cancers, especially for patients in European.

Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma.

Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

Dickkopf-1 is a novel prognostic biomarker for laryngeal squamous cell carcinoma

Conclusions: Dickkopf-1 (DKK1) is a novel prognostic biomarker for laryngeal squamous cell carcinoma (LSCC). DKK1 may be a promising strategy for the future treatment of LSCC metastasis and recurrence. Objectives: DKK1 is reportedly involved in the metastasis and invasion of several tumor types. This study aimed to investigate the prognostic value of DKK1 in LSCC. Methods: DKK1 expression was measured in Hep-2 cell lines, as well as in tumor and peritumoral tissues, using quantitative real-time PCR and western blot analyses. The role of DKK1 in LSCC was investigated by depleting DKK1 using small interfering RNAs. Tissue microarrays of 102 LSCC patient samples were employed to immunohistochemically detect expression of DKK1, vascular endothelial growth factor C (VEGF-C), and β-catenin. Prognostic significance was assessed using Kaplan–Meier survival estimates. Results: DKK1 expression was elevated in the Hep-2 cell line and tumor samples. DKK1 depletion decreased cell proliferation, migration, and invasiveness. High DKK1 expression was significantly associated with T and clinical stage, lymph node metastasis, and tumor size (p < 0.05). Increased DKK1 levels in LSCC tissues correlated with elevated VEGF-C and β-catenin. Multivariate analyses revealed that DKK1 was an unfavorable predictor of overall survival.

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer

The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 6 (KLK6) by immunohistochemistry in CRC to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK6 expression was evaluated by immunohistochemistry and an expression score was calculated for each case. In CRC, KLK6 expression was decreased compared to normal colonic mucosa. A statistically significant, positive association was observed between KLK6 and tumor stage (p=0.036), lymph node metastases (p=0.030), and liver metastases (p=0.025). Univariate analysis showed that KLK6 expression and stage had statistically significant correlation with disease-free survival (p=0.045 and p<0.001, respectively) and overall survival (p=0.027 and p<0.001, respectively). Cox multivariate analysis showed that KLK6 expression was an independent predictor of unfavorable overall survival (p=0.041). Kaplan–Meier survival curves showed that KLK6-positive patients have statistically significant lower disease-free and overall survival. In conclusion, KLK6 immunostaining is an independent prognostic marker in patients with CRC.