1.
Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: a study in Chinese patients with very small nodules.
Chen, C, Huang, X, Yin, W, Peng, M, Wu, F, Wu, X, Tang, J, Chen, M, Wang, X, Hulbert, A, et al
Clinical epigenetics. 2020;(1):39
Abstract
PURPOSE We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples. EXPERIMENTAL DESIGN Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP. RESULTS Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41-69% and 49-82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84-0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm. CONCLUSIONS Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage.
2.
Association of plasma visfatin with risk of colorectal cancer: An observational study of Chinese patients.
Chen, M, Wang, Y, Li, Y, Zhao, L, Ye, S, Wang, S, Yu, C, Xie, H
Asia-Pacific journal of clinical oncology. 2016;(1):e65-74
Abstract
AIM: To investigate the association between plasma visfatin levels and risk of early and advanced colorectal cancer (CRC). METHODS In total, 358 CRC patients and 286 controls were enrolled. According to the T factor of the TNM system. cancer patients were divided into two subgroups: early and advanced cancer. Levels of visfatin, anthropometric and metabolic parameters, which were classified as low, medium, and high, based on the tertile distributions in the control group, were determined. RESULTS The visfatin levels in patients with advanced and early cancer were higher than in controls (least significant difference test, P = 0.004 and 0.013, respectively). The patients in the highest tertile of visfatin concentration presented significantly higher odds for early and advanced CRC, adjusted for potential confounding factors (odds ratio 3.37; 95% CI, 1.93-8.37; P = 0.011; odds ratio 2.38; 95% CI: 1.82-8.35; P = 0.015, respectively). The visfatin level correlated significantly with waist:hip ratio (P < 0.05 for all) among case and control participants. Plasma visfatin levels in early and advanced CRC yielded a receiver operating characteristic curve area of 72 and 86%, respectively. The optimal sensitivity and specificity were 73% and 57% in discriminating between early CRC and normal controls while they were 76% and 68% in discriminating between advanced CRC and normal controls. CONCLUSION An increased level of visfatin was a strong risk factor for both early and advanced CRC in Chinese patients. Plasma visfatin levels might be a potential biomarker for CRC detection.
3.
High-density lipoprotein cholesterol as a predictor of poor survival in patients with nasopharyngeal carcinoma.
Liu, YY, Lin, SJ, Chen, YY, Liu, LN, Bao, LB, Tang, LQ, Ou, JS, Liu, ZG, Chen, XZ, Xu, Y, et al
Oncotarget. 2016;(28):42978-42987
Abstract
PURPOSE We aimed to assess the prognostic value of pretreatment high density lipoprotein cholesterol (HDL-C) levels in patients with nasopharyngeal carcinoma (NPC) and investigate the possible biological effects of these lipoproteins on NPC cells in vitro. EXPERIMENTAL DESIGN We examined the prognostic value of pretreatment HDL-C levels in 2443 patients with non-metastatic NPC from three independent institutions. The Cox proportional hazard model and log-rank test were used to analyze the correlation between HDL-C levels and overall survival (OS). Cell growth, colony formation, and apoptotic assays were used to determine the biological functions of HDL on NPC cells in vitro. All of the statistical tests were two-sided. RESULTS OS was decreased in patients with high pretreatment HDL-C levels compared with those with low HDL-C levels (P < 0.05). Similarly, a decreased OS was noted in advanced stage (stage III-IV), NPC patients with high pretreatment HDL-C levels (P < 0.01). Multivariate analyses indicated that HDL-C was an independent prognostic factor associated with shorter OS in training cohorts. These findings were confirmed in both independent validation cohorts (P < 0.01). In vitro experiments demonstrated that HDL could increase cell proliferation, invasion, and colony formation, which were largely dependent on the expression of its receptor SR-B1. Finally, HDL could enhance chemoresistance by protecting cancer cells from apoptosis. CONCLUSIONS Pretreatment HDL-C is a poor prognostic factor for patients with NPC. This effect may be associated with the ability of HDL to enhance proliferation, colony formation, migration, and chemoresistance in NPC cells.