Biomarkers For Prediction Of Metastasis Research Articles

Clinical and prognostic value of neutrophil-lymphocyte ratio for patients with thyroid cancer: A meta-analysis.

Background:Although the malignant degree is relatively low and overall prognosis is excellent, some patients with thyroid cancer still experience metastasis during the follow-up, which leads to their possible death. Pretreatment neutrophil-to-lymphocyte ratio (NLR) has been recommended as a biomarker for the prediction of metastasis and prognosis in patients with cancers. However, its value in thyroid cancer remains inconclusive. This study aimed to comprehensively evaluate the prognostic and clinicopathological significance of NLR for thyroid cancer by a meta-analysis.Methods:Eligible studies were identified by searching PubMed, EMBASE, and Cochrane Library databases. The associations between NLR level and disease-free survival (DFS) or clinicopathological parameters were estimated by calculating hazard ratio (HR) or effect size with 95% confidence interval (CI).Results:Nine studies consisting of 3081 patients were enrolled. Results of meta-analysis showed that elevated NLR was not significantly associated with unfavorable DFS overall, but subgroup analysis of multivariate-adjusted studies demonstrated an elevation in pretreatment NLR predicted poor DFS (HR = 3.51, 95%CI = 1.42–8.70). Overall, a high level of NLR was significantly correlated with larger tumor size (standardized mean difference [SMD] = 0.49, 95%CI = 0.33–0.64), and metastasis status (risk ratio [RR] = 1.70, 95%CI = 1.10–2.64). The association with tumor size was still significant in the stratified analyses by country and histology type (Asian: SMD = 0.719, 95%CI = 0.44–0.98; non-Asian: SMD = 0.36, 95%CI = 0.17–0.56; medullary thyroid carcinoma: SMD = 0.57, 95%CI = 0.09–1.05; papillary thyroid carcinoma: SMD = 0.48, 95%CI = 0.31–0.64). The association between NLR and metastasis was only significant for papillary thyroid carcinoma subtype (RR = 1.82, 95%CI = 1.04–3.20).Conclusion:Pretreatment NLR may serve as an excellent biomarker for prediction of tumor growth, metastasis, and prognosis in patients with thyroid cancer.

Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer.

BackgroundTo identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC).Materials and MethodsSerum exosomes were isolated from patients with metastatic CRC (n = 34) and non‐metastatic CRC (n = 108) by ultracentrifugation and characterized using transmission electron microscopy, qNano, and Western blot. Differential exosomal miRNAs were screened by sequencing and validated by qPCR in metastatic and non‐metastatic CRC patients.ResultsAfter sequence analysis, KEGG analysis showed that differential genes were associated with Rap1 signaling pathway and pathways in cancer, 6 upregulated exosomal miRNAs (miR‐224‐5p, miR‐548d‐5p, miR‐200a‐3p, miR‐320d, miR‐200b‐3p, and miR‐1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miR‐27a‐5p) were screened with fold change >1.5, among which miR‐320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miR‐320d could significantly distinguish metastatic from non‐metastatic CRC patients (P = .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miR‐320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC.ConclusionSerum exosomal miR‐320d is a promising non‐invasive diagnostic biomarker for distinguishing metastatic from non‐metastatic CRC.

Abstract 2765: Exosomal miRNAs as circulating biomarkers for prediction of metastasis in stage II/III gastric cancer

Abstract Background: Metastasis is the fatal character of cancer, leading to mortality of gastric cancer. In recent years, exosomes have been reported as extracellular vesicles secreted by cells. They contain various biological molecules including miRNAs from the original cells. Exosomal miRNAs are significant for pre-metastatic niche formation, as they can change the microenvironment and make it favorable for future metastasis. Therefore, the aim of this study was to identify dysregulated exosomal miRNAs as circulating biomarkers for prediction of metastasis of gastric cancer. Materials and Methods: Pre-treatment serum samples of 36 metastatic patients and 55 non-metastatic patients with stage II/III gastric cancer were collected. Exosomes were extracted and validated by western blot, transmission electron microscope and nanoparticle tracking analysis. MiRCURY LNATM miRNA miRNome PCR Array (containing 752 miRNAs) was performed in three pairs of serum exosomes. Each pair samples were with the same stage, race, gender and similar age. These three pairs of samples represented stage II, IIIA or IIIB gastric cancer, respectively. A panel of commonly dysregulated exosomal miRNAs was released from the PCR Array. Expressions of exosomal miRNAs were validated in the remaining 33 metastatic and 52 non-metastatic patients by RT-qPCR, as well as in gastric cancer cell culture medium and cell lines. Results: By comparing the expressions of exosomal miRNAs between the metastatic patients and matched non-metastatic ones, 13 upregulated and 6 downregulated miRNAs were released after normalization with miR-16-5p and miR-93-5p. Among these miRNAs, 7 of them were selected for further validation according to their fold changes, p-values and association with cancer development. MiR-379-5p and miR-410-3p were validated to be significantly upregulated in metastatic patients (P<0.01). Sensitivity, specificity and AUC were 67.31%, 69.70% and 0.6894 for miR-379-5p, and 65.38%, 66.67% and 0.6719 for miR-410-3p. Higher expression of serum exosomal miR-379-5p or miR-410-3p showed shorter overall survival of the patients (P<0.05). It was also found that miR-379-5p and miR-410-3p expressed significantly higher in gastric cancer cell culture medium comparing with gastric cancer cells. Conclusions: Exosomal miRNAs are dysregulated in the serum of metastatic gastric cancer patients before they are clinically diagnosed. Upregulation of serum exosomal miR-379-5p and/or miR-410-3p are promising circulating biomarkers for prediction of metastasis in stage II/III gastric cancer. Citation Format: Xin Liu, Kent-Man Chu. Exosomal miRNAs as circulating biomarkers for prediction of metastasis in stage II/III gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2765.

Prospective validation of DACH2 as a novel biomarker for prediction of metastasis and prognosis in muscle-invasive urothelial carcinoma of the bladder

Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80–96] versus 19% [95% CI 7–31], p < 0.001; 5-year OS: 93% [95% CI 87–99] versus 37% [95% CI 23–51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.

Biomarkers for prediction of metastasis and recurrence of hepatocellular carcinoma

Biomarkers for prediction of metastasis and recurrence of hepatocellular carcinoma