Cancer Biomarkers - Volume 26, issue 4

Authors: Ma, Ge | Song, Guoxin | Zou, Xuan | Shan, Xia | Liu, Qingxie | Xia, Tiansong | Zhou, Xin | Zhu, Wei

Article Type: Research Article

Abstract: OBJECTIVE: To determine the utility of plasma microRNAs (miRNAs) as biomarkers in cervical cancer (CC). METHODS: Some studies were conducted about the specific expression of plasma miRNAs in the diagnosis of CC. Plasma samples of 97 CC patients and 87 normal controls (NCs) were used to identify dysregulation of miRNAs in the training, testing, and external validation phases. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of identified individual miRNAs and miRNA panels for the diagnosis of CC. Expression levels of specific miRNAs were …also examined in plasma exosomes and tissue samples of CC patients. RESULTS: Four plasma miRNAs (miR-146a-5p, miR-151a-3p, miR-2110 and miR-21-5p) which showed up-regulation were identified and validated in CC patients. A panel of the four miRNAs were constructed as potential diagnostic markers for CC. The AUCs of the panel of these four-miRNAs for the training, testing, and external validation phases were 0.911, 0.774, and 0.786, respectively. miR-146a-5p and miR-21-5p levels were all up-regulated in CC tissue specimens, whereas miR-146a-5p, miR-151a-3p, and miR-2110 levels were up-regulated in plasma exosomes. CONCLUSION: The signature of the four-miRNAs identified in peripheral plasma is a promising novel biomarker for the diagnosis of CC. Show more

Keywords: Plasma microRNA, cervical cancer, diagnosis, exosome, qRT-PCR

DOI: 10.3233/CBM-190256

Citation: Cancer Biomarkers, vol. 26, no. 4, pp. 491-500, 2019

Authors: Li, Jian | Jin, Boxun | Wang, Tiezheng | Li, Wenlei | Wang, Zhenshun | Zhang, Haitao | Song, Yunjun | Li, Ning

Article Type: Research Article

Abstract: BACKGROUND: The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential. OBJECTIVE: The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC. METHODS: Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with …chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC. RESULTS: Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects. CONCLUSIONS: The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis. Show more

Keywords: Hepatocellular carcinoma, MiRNAs, serum, hepatitis c virus, liver cirrhosis

DOI: 10.3233/CBM-181970

Citation: Cancer Biomarkers, vol. 26, no. 4, pp. 501-512, 2019

Authors: Manai, Maroua | Abdeljaoued, Syrine | Goucha, Aïda | Adouni, Olfa | Bettaieb, Ilhem | Bouzaien, Hatem | Rahal, Khaled | Birnbaum, Daniel | Bertucci, François | Gamoudi, Amor

Article Type: Research Article

Abstract: BACKGROUND: Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial. OBJECTIVE: Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) in MBC and to investigate its prognostic value. MATERIALS AND METHODS: MARCKS protein expression in tumor and stromal cells was analyzed by immunohistochemistry (IHC) in a retrospective series of 96 pre-chemotherapy MBC samples and 80 normal breast samples, from Tunisian patients treated at Salah Azaiez Institute. Correlations were searched between MARCKS expression and clinicopathological features including overall survival (OS). …RESULTS: MARCKS was overexpressed in epithelial tumor cells in 66% of the MBC samples versus 26% of normal samples (p = 1.40 × 10 - 7 ). Such positive MARCKS expression in epithelial tumor cells was associated with positive HER2 status (p = 4.0 × 10 - 3 ). It was associated with shorter OS in uni-and multivariate analysis. By contrast, stromal IHC MARCKS expression was correlated only with tumor grade. CONCLUSION: MARCKS tumor cell overexpression might in part explain the aggressiveness and the poor prognosis of MBC. MARCKS can represent a potential therapeutic target for MBC. Show more

Keywords: MARCKS, expression, male breast cancer, immunohistochemistry, survival

DOI: 10.3233/CBM-190637

Citation: Cancer Biomarkers, vol. 26, no. 4, pp. 513-522, 2019

Authors: Lv, Min | Wang, Fen | Wang, Xiaoyan | Zhang, Cuilan

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to assess the diagnostic value of human epididymis protein 4 (HE4) in the pleural effusion of lung cancer patients. METHODS: HE4 protein in the pleural effusion of 60 lung cancer patients was measured by electrochemiluminescence, in parallel with those from 56 patients with benign lung disease, and the association with malignant pleural effusion was evaluated. RESULTS: The level of HE4 in samples from lung cancer patients was significantly higher than the level for those with benign lung lesions (P =  0.001) and patients with lung …adenocarcinoma showed significantly higher levels of HE4 than those with squamous cell carcinoma and small cell carcinoma (P =  0.002 and P =  0.034, respectively). Using an optimal threshold of 652.2 pmol/L, the HE4 level distinguished malignant lung cancer from benign lesions with a sensitivity of 78.3% and a specificity of 75.0%. Moreover, the HE4 level differentiated adenocarcinoma from benign lesions with a sensitivity of 75.9% and a specificity of 85.7% when a threshold of 744.05 pmol/L was used. However, there was no significant difference in the 2 year survival rates of lung cancer patients with high and low HE4 concentrations in pleural fluid (P =  0.882). In addition, there was no significant difference in HE4 levels between tuberculous and inflammatory pleural effusions (P =  0.309). CONCLUSION: HE4 in the pleural fluid of lung cancer patients can be valuable in the diagnosis of malignant pleural effusion; however, it does not correlate with the prognosis of patients. Show more

Keywords: Lung cancer, malignant pleural effusion, diagnosis, prognosis, HE4, electrochemiluminescence

DOI: 10.3233/CBM-190840

Citation: Cancer Biomarkers, vol. 26, no. 4, pp. 523-528, 2019