Cancer Biomarkers - Volume 22, issue 2

Authors: Latini, Giuseppe | De Felice, Claudio | Barducci, Alessandro | Dipaola, Lucia | Gentile, Mattia | Andreassi, Maria Grazia | Correale, Mario | Bianciardi, Giorgio

Article Type: Research Article

Abstract: Cancer is the most important cause of death worldwide, and early cancer detection is the most fundamental factor for efficacy of treatment, prognosis, and increasing survival rate. Over the years great effort has been devoted to discovering and testing new biomarkers that can improve its diagnosis, especially at an early stage. Here we report the potential usefulness of new, easily applicable, non-invasive and relatively low-cost clinical biomarkers, based on abnormalities of oral mucosa spectral reflectance and fractal geometry of the vascular networks in several different tissues, for identification of hereditary non-polyposis colorectal cancer carriers as well for detection of other …tumors, even at an early stage. In the near future the methodology/technology of these procedures should be improved, thus making possible their applicability worldwide as screening tools for early recognition and prevention of cancer. Show more

Keywords: Clinical biomarkers, cancer, oral mucosal network abnormalities, fractal analysis, oral mucosal spectral reflectance

DOI: 10.3233/CBM-170050

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 179-198, 2018

Authors: Fricke, A. | Cimniak, A.F.V. | Ullrich, P.V. | Becherer, C. | Bickert, C. | Pfeifer, D. | Heinz, J. | Stark, G.B. | Bannasch, H. | Braig, D. | Eisenhardt, S.U.

Article Type: Research Article

Abstract: BACKGROUND: Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish dedifferentiated liposarcoma patients from healthy controls and lipoma patients. METHODS: Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma (n = 6) and of healthy donors (n = …4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients. RESULTS: As shown by the microarray, two miRNAs (miR-3613-3p, miR-4668-5p) were shown to be significantly upregulated (fold change: > 2.5; p < 0.05) in patients with dedifferentiated liposarcoma (n = 6) as compared to healthy controls (n = 4). miR-3613-3p was further validated by qRT-PCR to be significantly upregulated in dedifferentiated liposarcoma patients compared to an independent cohort of healthy controls (n = 3) and lipoma patients (n = 5). CONCLUSION: We identified a specific whole blood miRNA (miR-3613-3p) that may serve to distinguish between dedifferentiated liposarcoma patients and healthy controls, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma. Show more

Keywords: Whole-blood-RNA, miRNA, dedifferentiated liposarcoma, biomarker, liquid biopsy

DOI: 10.3233/CBM-170496

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 199-207, 2018

Authors: Tian, Chunmei | Zhang, Lin | Li, Xiaohua | Zhang, Yanjun | Li, Jianchang | Chen, Liang

Article Type: Research Article

Abstract: BACKGROUND: Abnormal expression of miR-192 has been observed in a variety of human cancers, but the expression pattern of miR-192 and its prognostic value in pediatric acute myeloid leukemia (AML) is poorly known. OBJECTIVE: This study was to explore the expression status of miR-192 and its clinical significance in pediatric patients with AML. METHODS: Quantitative RT-PCR was carried out to detect miR-192 expression level in the serum from 97 AML cases and 50 healthy controls. RESULTS: The results showed that downregulation of serum miR-192 was observed in pediatric AML patients and …strongly correlated with aggressive clinical features. Increased serum miR-192 expression occurred more frequently in the AML subjects with favorable risk cytogenetics. Moreover, serum miR-192 expression showed good performance to screen pediatric AML subjects from normal controls. Furthermore, serum miR-192 was identified as a independent prognostic indicator for both overall survival and event free survival. In addition, low serum miR-192 expression significantly contributed to poor prognosis in the whole cohort of AML patients or the AML patients with intermediate-risk cytogenetics. CONCLUSIONS: Collectively, serum miR-192 potentially can be a reliable biomarker for the diagnosis and prognosis in pediatric AML. Show more

Keywords: Acute myeloid leukemia, MiR-192, pediatric, prognosis

DOI: 10.3233/CBM-170657

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 209-215, 2018

Authors: Ding, Shimei | Qu, Wei | Jiao, Yang | Zhang, Jing | Zhang, Chunhong | Dang, Shuangsuo

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the expression and role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) in papillary thyroid carcinoma (PTC). METHODS: The relative expression levels of lncRNA SNHG12 (hereinafter referred to as SNHG12) in 42 pairs of PTC tissues and para-carcinoma tissues were detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). SNHG12 specific interference sequences were designed and synthesized. The relative expression level and transfection efficiency of SNHG12 in PTC cells were detected via qRT-PCR. After the interference in SNHG12 expression, the change in cell proliferation capacity was detected via methyl …thiazolyl tetrazolium (MTT) assay, the change in cell cycle distribution was detected via flow cytometry, the changes in cell migration and invasion capacities were detected via Transwell assay and wound healing assay, and the changes in expressions of molecular markers of Wnt/β -catenin pathway were detected via Western blotting. The pulmonary metastasis model of nude mice was established, and the changes in migration and invasion capacities of tumor cells were studied via the in-vivo experiment after the interference in SNHG12 expression. RESULTS: The results of qRT-PCR showed that the SNHG12 expression was up-regulated in 30 pairs of PTC tissues and cells. The results of MTT assay showed that the cell proliferation capacity was inhibited after the interference in SNHG12. The results of flow cytometry showed that the cell cycle progression was blocked in G1-G0 phase after the knockdown of SNHG12 expression. The results of Transwell assay and Western blotting showed that the interference in SNHG12 could inhibit the invasion and metastasis capacities of tumor cells through influencing the Wnt/β -catenin signaling pathway. Metastatic tumor model of nude mice showed that SNHG12 could affect the invasion and metastasis of tumor cells in vivo . CONCLUSION: The SNHG12 expression is relatively high in PTC tissues and cells. In-vivo /in-vitro experiments prove that SNHG12 can promote the proliferation and metastasis of PTC cells through influencing the Wnt/β -catenin signaling pathway. Show more

Keywords: Papillary thyroid carcinoma, lncRNA SNHG12, proliferation, invasion, metastasis, Wnt/β-catenin signaling pathway

DOI: 10.3233/CBM-170777

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 217-226, 2018

Authors: Wang, Yingchao | Jing, Wei | Ma, Weijie | Liang, Chunzi | Chai, Hongyan | Tu, Jiancheng

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the most common solid tumor in global range, with high degree of malignancy and poor prognosis. But the relationship between the expression of GAS5-AS1 and HCC is not documented. This study aimed to profile GAS5-AS1 expression signature and then to explore its clinical significance in HCC. METHODS: Quantitative real-time PCR (RT-qPCR) was performed to detect the expression of GAS5-AS1 in 83 pairs of HCC surgical tissues and adjacent normal liver tissues. We also performed RT-qPCR on plasma samples of 156 patients and 58 healthy controls. RESULTS: We found that GAS5-AS1 …was down-regulated in HCC tissues (P < 0.01). Correlation analysis showed that the expression of GAS5-AS1 was notably associated with differentiation (High/Moderate vs Low, P = 0.031), tumor-node-metastasis (TNM) stage (I∼ II vs III∼ IV, P = 0.020) and glucose levels (< 6.2 vs ≧ 6.2, P = 0.047) in HCC patients. The overall survival analysis showed that patients with lower GAS5-AS1 expression had a relatively poor prognosis. Univariate and multivariate analysis elaborated that GAS5-AS1 was an independent prognostic factor for HCC patients. The area under the ROC (AUC ROC ) demonstrated that GAS5-AS1 presented a high accuracy (AUC = 0.824, 95% CI: 0.741–0.906) for distinguishing HCC from the cirrhosis. When differentiating HCC cases with AFP < 200 ng/ml from the cirrhosis and hepatitis B whose AFP levels were also below 200 ng/ml, GAS5-AS1 had the high sensitivity (89.5%, 89.5%, respectively). CONCLUSIONS: GAS5-AS1 could be considered as a potential prognostic and diagnostic marker in HCC. However, the potential clinical application value of GAS5-AS1 still needs to be further illustrated. Show more

Keywords: Hepatocellular carcinoma, long non-coding RNA, GAS5-AS1, prognosis, diagnosis

DOI: 10.3233/CBM-170781

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 227-236, 2018

Authors: Wang, Yu | Jiang, Xiaorong | Wang, Shasha | Yu, Haixia | Zhang, Tingting | Xu, Shuan | Li, Wenlong | He, Ellen | Skog, Sven

Article Type: Research Article

Abstract: BACKGROUND: People with biomarkers above cut-off values normally have higher risk to develop pre-malignancies and malignancies. OBJECTIVE: Here we investigate if serological TK1 protein (STK1p), AFP, CEA and PSA below cut-off values predict development of pre-cancer. METHODS: The mean values and the concentration distribution of STK1p, AFP, CEA and PSA were determined in a cohort of 56,178 persons participating a health screening group, consist of people with non-tumor diseases, pre-malignancy and diseases associated with the risk process of malignancy. A health disease-free group (n = 428) was selected among …the 56,178 participants and used as controls. RESULTS: The STK1p below cut-off value (⩽ 2 pM) showed partly (51.6%) an almost normal concentration distribution and partly (43.9%) an extensive tail in the health screening group, which was not found in the disease-free group. Due to the extensive tail in the distribution, the mean value of STK1p increased significantly (p = 0.0001) from 0.38 ± 0.30 pM in the health disease-free group to 0.69 ± 0.55 pM in the group below the cut-off value. No significantly differences in the concentration distribution and the mean values among gender and ages were observed. On the other hand, there were no difference in the concentration distributions and the mean values of AFP, CEA and PSA between the health disease – free group and the group below cut-off values, as well as between gender and ages. Of interest, the elevated mean value of STK1p of the group below the cut-off value was correlated to pre-malignancy and diseases associated with the risk process of malignancy in liver and prostate. No such correlations were found with AFP, CEA and PSA. CONCLUSION: STK1p is a potential proliferating biomarker for early discover of persons in the risk to develop or already have pre-malignancies or diseases associated with the risk process of malignancy. Show more

Keywords: Thymidine kinase 1 (TK1), serum thymidine kinase 1 (STK1p), AFP, CEA, PSA, pre-malignancy

DOI: 10.3233/CBM-170846

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 237-247, 2018

Authors: Lu, Rongzhao | Zhang, Jie | Zhang, Wei | Huang, Yanhua | Wang, Ningxia | Zhang, Qing | Qu, Shaohua

Article Type: Research Article

Abstract: BACKGROUND: Long noncoding RNA HOTAIR has been detected in the serum of patients with various malignances and may be served as novel biomarker for diagnosis and prognosis prediction of breast cancer. However, the value of circulating HOTAIR to predict the response to neoadjuvant chemotherapy (NAC) remains unclear. OBJECTIVE: In the present study, we analyzed whether pretreatment circulating HOTAIR levels predict the response to NAC and investigated prognostic impact of circulating HOTAIR on disease-free survival (DFS) in breast cancer patients treated with NAC. METHODS: Circulating HOTAIR levels in the serum of 112 breast cancer …patients before NAC were measured using quantitative real-time PCR. The correlation of circulating HOTAIR with the clinicopathologic status and the response to NAC were analyzed. Kaplan-Meier survival analysis and log-rank test were used to estimate the DFS. RESULTS: In 112 serum samples obtained before NAC, high circulating HOTAIR was associated with larger tumor size, more positive lymph nodes as well as more distant metastasis. However, there was no significant correlation between the circulating HOTAIR levels and age, Ki67 status or hormone receptor. Furthermore, patients with high circulating HOTAIR achieved less clinical response as well as pathologic complete response than those with low circulating HOTAIR (p < 0.05). The Kaplan-Meier survival curve with a median follow-up of 48 months demonstrated that patients with high circulating HOTAIR expression had a worse disease-free survival than those with low circulating HOTAIR (log-rank p = 0.012). CONCLUSIONS: High circulating HOTAIR level correlates with less response to neoadjuvant chemotherapy as well as a worse prognosis in breast cancer patients. Therefore, the present study provides a favorable basis to use circulating HOTAIR as a predictor of neoadjuvant chemotherapy response. Show more

Keywords: Circulating HOTAIR, breast cancer, neoadjuvant chemotherapy

DOI: 10.3233/CBM-170874

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 249-256, 2018

Authors: Akinbo, David Bolaji | Onyeaghala, Augustine A. | Emomidue, Jennifer Ochuko | Ogbhemhe, Stephanie Okhuriafe | Okpoli, Henry Chijindu

Article Type: Research Article

Abstract: BACKGROUND: The Indian borage (Plectranthus amboinicus ) also called Oregano contains many effective antioxidants, which includes caffeic acid, rosmarinic acid and flavonoids. It has been employed in traditional medicine for its several health benefits including the prevention and cure of many debilitating diseases. Anti-inflammatory properties of Plectranthus amboinicus grown within this environment have not been adequately explored. OBJECTIVE: The protective and therapeutic effects of Oregano against endotoxaemia and inflammation were evaluated using lipopolysaccharide (LPS)-induced rat models. MATERIALS AND METHODS: A total of 30 Wistar rats were randomly selected for this study and …divided into six groups, with each group having 5 rats. Inflammation was induced on appropriate animal groups using LPS injection at a concentration of 4 mg/kg. Aqueous leaf extract of Indian borage was administered orally in four doses (100 mg/kg, 200 mg/kg, 400 mg/kg post-LPS exposure and 150 mg/kg pre-LPS exposure) to respective treatment rat groups. Haematological profile, toxicity profile of liver and kidney and levels of biomarkers of inflammation were assayed using standard methods. RESULTS: Rats injected with LPS showed severe anaemia and marked leucopoenia with significant decrease in monocytes compared to the control group (p < 0.05). There was increased expression of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α ) (p < 0.05) in the peripheral circulation of rats exposed to LPS. Treatment with Indian borage significantly (p < 0.05) reduced the toxic effects in the LPS-treated animals and attenuated the increase in the expression of circulating proinflammatory cytokines; tumor necrosis factor alpha (TN-Fα ) and interleukin-8 (IL-8) caused by LPS. Indian borage pretreatment also significantly (p < 0.05) counteracted the associated haematological dyscrasias caused by exposure to LPS. The extract elicited a significant protective effect on the kidney and liver as evidenced by the decreased renal markers and hepatic enzyme activities when compared with the control. The extract demonstrated protective and suppressive role against the overexpression of inflammatory mediators by ameliorating the induced inflammation and endotoxaemic conditions in the affected rat groups thereby validating its folkloric use. CONCLUSION: Our study thus reveals that the extract might be an active, natural and non-toxic drug lead against endotoxaemia-induced inflammation and toxicity. Show more

Keywords: Anti-inflammatory, haematological indices, Indian borage, lipopolysaccharide, phytochemical constituents

DOI: 10.3233/CBM-170893

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 257-265, 2018

Authors: Liu, Qingyun | Xiang, Ying | Yuan, Shuai | Xie, Weijia | Li, Chengying | Hu, Zeyao | Wu, Na | Wu, Long | Yu, Zubin | Bai, Li | Li, Yafei

Article Type: Research Article

Abstract: BACKGROUND: Biomarker studies revealed important clinical significance of exosome for cancer patients. However, there is currently no consensus on exosome quantification methods. METHODS: Bicinchoninic acid (BCA) method, acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were utilized to quantify 20 plasma exosome samples, and interrelations between these three methods were explored. Associations of plasma exosome levels with characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients were investigated. RESULTS: Results of the three methods for exosome quantification were significantly correlated with each other. Correlation coefficient between AChE and NTA (r = …0.79, P < 0.001) was greater than that between BCA and NTA (r = 0.64, P = 0.003). Plasma exosome levels of 208 NSCLC patients were then quantified with AChE method. Exosome level was significantly associated with tumour stage (P < 0.001) and the history of chronic obstructive pulmonary disease (P = 0.023). Cox proportional hazard analysis demonstrated that higher exosome level was independently associated with poorer overall survival (P = 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05–2.83). CONCLUSIONS: Plasma exosome level correlates with tumor stage and the history of chronic obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC. Show more

Keywords: Non-small-cell lung cancer, exosome, quantification, prognosis, biomarker

DOI: 10.3233/CBM-170955

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 267-274, 2018

Authors: Zhu, Zunwei | Xu, Lieyu | Wan, Yong | Zhou, Jie | Fu, Donghui | Chao, Haichao | Bao, Kunwang | Zeng, Tao

Article Type: Research Article

Abstract: Bladder cancer is derived from bladder mucosa and is the most common malignant tumor in urinary system. Long non-coding RNA (lnc-RNA) has high tissue specificity and can participate in cell proliferation and differentiation at various levels, and plays critical roles in occurrence of malignant tumors. This study aims to investigate the suppression of E-cadherin expression by lnc-RNA H19 to enhance bladder cancer metastasis. qRT-PCR was applied to analyze differential expression of lnc-RNA H19 in different bladder cancer tissues and tumor adjacent tissues. Patients clinical data were collected to analyze the correlation between H19 expression level and patient’s clinical stage, …tumor metastasis. RNA interference was employed to examine the effect of H19 on E-cadherin expression. The regulation of cancer metastasis was investigated on an animal model. H19 expression level was significantly higher in bladder cancer tissue compared to adjacent tissues (p < 0.05), and is correlated with advanced clinical stage (p < 0.05). In those metastatic patients, H19 expression level is significantly higher than those without metastasis (p < 0.05). RNA interference is applied to knockdown H19 expression in bladder cancer cell, and found potentiated E-cadherin expression (p < 0.05), accompanied with weakened metastatic potency (p < 0.05). H19 expression is up-regulated in bladder cancer, and is probably related with cancer clinical stage and metastasis. Cell transfection reveals up-regulation of E-cadherin expression in bladder cancer cells when H19 expression is suppressed, accompanied with weakened metastasis potency. Show more

Keywords: Bladder cancer, lnc-RNA-H19, E-cadherin, tumor metastasis

DOI: 10.3233/CBM-170998

Citation: Cancer Biomarkers, vol. 22, no. 2, pp. 275-281, 2018