Cancer Biomarkers - Volume 28, issue 1

Authors: Wang, Xiaonan | Bi, Xiaomin | Huang, Xing | Wang, Bijun | Guo, Qianying | Wu, Zhengsheng

Article Type: Research Article

Abstract: BACKGROUND: ARHGDIB, a Rho GDP dissociation inhibitor protein, has been reported playing critical roles in regulation of multiple biological responses. However, whether ARHGDIB serves as a valuable biomarker in cancer is little known so far, especially in breast cancer. OBJECTIVE: In this study, we aimed to investigate the importance of ARHGDIB in breast cancer, including but not limited to biomarker-like role, as well as potential mechanisms. METHODS: Total 100 breast cancer samples and 100 benign breast disease samples were enrolled and underwent detailed pathological assessment and IHC analysis. Human breast cancer cell lines …and epithelial cell line were subjected to siRNA-mediated knock-down, RT-qPCR, western blot, MTT staining, cell cycle assay, transwell analysis respectively. RESULTS: We observed the expression of ARHGDIB is significantly higher in human breast cancer tissues compared with the benign tissues. ARHGDIB expression was positively correlated with tumor size, lymph node metastasis and TNM stage in breast cancer patients. Moreover, ARHGDIB depletion decreased proliferation, migration and invasion of breast cancer cells. Furthermore, we found ARHGDIB mediated epithelial-mesenchymal transition, and MMP2 is the key downstream effector of ARHGDIB. CONCLUSIONS: Hence, our results suggested the significance and predictive role of ARHGDIB in breast cancer. High expression of ARHGDIB indicated the poor prognosis for breast cancer patients. Show more

Keywords: ARHGDIB, biomarker, breast cancer, EMT, prognosis

DOI: 10.3233/CBM-190562

Citation: Cancer Biomarkers, vol. 28, no. 1, pp. 101-110, 2020

Authors: Guan, Gege | Wang, Yuehua | Sun, Qiushi | Wang, Ling | Xie, Fei | Yan, Jiayin | Huang, Huajun | Liu, Huijie

Article Type: Research Article

Abstract: BACKGROUND: Cancer recurrence for patients with early breast cancer is significant. Patients will benefit from more non-invasive modes of monitoring and we aim to study the feasibility of urinary circulating tumor DNA (ctDNA) to monitor for residual disease (MRD). METHODS: In this longitudinal study, 300 early breast cancer patients were recruited prospectively. Measurements were taken prior to treatment and at different time points thereafter for a total of 8 measurements. Comparisons were made with healthy volunteers and patients without detectable mutations in urine specimens. Disease free relapse were correlated to both urinary DNA quantity and ctDNA …concentration. RESULTS: Baseline index measurements showed 38% of patients with detectable mutations. The concordance with biopsy tissues was 97.3%. Overall, breast cancer patients had higher urinary DNA compared with healthy volunteers. Over time, fluctuations in urinary DNA was negligible in healthy volunteers, indicating the stability of the marker. Among the patients with detectable mutations, we observed that higher urinary DNA quantity measurements at 6-month and patients with positive mutations were associated with greater risk of relapse. Hazard ratios for patients in this category was 1.65 (95% CI 1.26–2.16) and 1.98 (95% CI 1.48–2.63) respectively. CONCLUSION: Urinary DNA offers non-invasive probing and real-time monitoring of breast cancer relapse. Our results demonstrated clear clinical relevance in breast cancer and significant risk profiling of early breast cancer patients. This potentially aids to complement current cancer relapse monitoring and may help in early intervention. Show more

Keywords: Breast cancer, biomarker, MRD, disease relapse, circulating DNA

DOI: 10.3233/CBM-190523

Citation: Cancer Biomarkers, vol. 28, no. 1, pp. 111-119, 2020

Authors: Wang, Yitao | Jiang, Feifei | Wang, Jian | Fu, Yongxing | Li, Yuanyuan | Li, Feng

Article Type: Research Article

Abstract: BACKGROUND: Non-small cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are currently considered as novel targets and tools in cancer therapy. OBJECTIVE: The aim of this study was to investigate the expression level and functional role of miR-519a in NSCLC, as well as its clinical values. METHODS: One hundred and two patients with NSCLC were recruited. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-519a. Kaplan-Meier survival and Cox regression analyses were conducted to explore the prognostic significance of miR-519a in NSCLC. …MTT and Transwell assays were used to detect the effect of miR-519a on NSCLC cell proliferation, migration, and invasion. RESULTS: MiR-519a was significantly downregulated in NSCLC tissues, as well as NSCLC cell lines. The expression level of miR-519a was prominently associated with lymph node metastasis and TNM stage. Kaplan-Meier analysis suggested that low miR-519a expression was closely associated with shorter overall survival. Multivariate Cox regression analysis demonstrated that miR-519a expression level and TNM stage were two independent prognostic factors for 5-year overall survival in NSCLC patients. In vitro study, miR-519a significantly inhibited the proliferation, migration, and invasion of NSCLC cells. STAT3 was proved to be the target gene of miR-519a. CONCLUSIONS: MiR-519a functions as a tumor suppressor and inhibits tumor progression of NSCLC via targeting STAT3. MiR-519a may act as a prognostic biomarker and therapeutic target for NSCLC. Show more

Keywords: MicroRNA-519a, prognosis, progression, non-small cell lung cancer

DOI: 10.3233/CBM-190672

Citation: Cancer Biomarkers, vol. 28, no. 1, pp. 121-128, 2020