Cancer Biomarkers - Volume 24, issue 4

Authors: Laxmi, Aishwarya | Gupta, Pawan | Gupta, Jeena

Article Type: Other

Abstract: Cancer, a deadly disease is characterized by abnormal cell growth with the potential to invade to other parts of the body. Most cancers start due to changes at gene level that happen over a person’s lifetime when DNA repair system becomes faulty. CCDC6, one of the players in DNA repair system acts as a tumor suppressor gene. It was originally identified in chimeric genes caused by chromosomal translocation involving RET proto-oncogene in some thyroid tumors. Different fusion chimers with different proto-oncogenes like RET are known for CCDC6 which hampered its function. Further, CCDC6 is recognized as a pro-apoptotic phosphoprotein, which …is an ATM substrate responsive to genotoxic stress. In this article, we reviewed the published literature to characterize CCDC6 fusions with proto-oncogenes and the role of natural phytochemicals which can potentially alter CCDC6 activity and thus can prove beneficial for cancer patients. Show more

Keywords: CCDC6, cancer, chimeric protein, DNA repair, proto-oncogenes

DOI: 10.3233/CBM-181601

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 383-393, 2019

Authors: Li, Xue-Feng | Zhao, Guo-Qing | Li, Long-Yun

Article Type: Research Article

Abstract: BACKGROUND: Osteosarcoma (OS) is the most commonly occurred primary bone malignancy with high incident rates among children and adolescents. In pharmacologic treatment, the drug ginsenoside has been shown to exert anticancer effects on several malignant diseases. The purpose of this research was to investigate the effect of ginsenoside on the apoptosis and proliferation of human OS MG-63 and Saos-2 cells by regulating the expression of β -catenin. METHODS: Human OS MG-63 and Saos-2 cells were assigned into control group, and four groups with treatment by varying concentrations (12.5 μ g/mL, 25 μ …g/mL, 50 μ g/mL and 100 μ g/mL) of ginsenoside, respectively. Cell growth after treatment was observed through cell slides. The proliferation rate of MG-63 and Saos-2 cells in each group was detected by CCK-8. After cell transfection at 48 h, cell cycle and cell apoptosis were detected by FITC-Annexin V staining and flow cytometry. The protein and mRNA expressions of β -catenin, Cyclin D1, Bcl-2, Bax and cleaved caspase-3 were detected by RT-qPCR and western blot analysis. RESULTS: With increased exposure and concentration of ginsenoside, the cell density, total cell numbers and the absorbance of MG-63 and Saos-2 cells gradually decreased. FITC-Annexin V and FITC-Annexin V/PI staining demonstrated that the cell proportion at S phase decreased, whereas the total apoptotic rate of MG-63 and Saos-2 cells was increased. Furthermore, RT-qPCR and western blot analysis highlighted a gradual decrease in protein and mRNA expressions of β -catenin, Bcl-2 and Cyclin D1, while an elevation in those of Bax and cleaved caspase-3. CONCLUSION: The results of this study demonstrate that ginsenoside inhibits proliferation and promotes apoptosis of human OS MG-63 and Saos-2 cells by reducing the expressions of β -catenin, Bcl-2 and Cyclin D1 and increasing the expression of Bax and cleaved caspase-3. Show more

Keywords: Ginsenoside, osteosarcoma, MG-63 cells, Saos-2 cells, proliferation, apoptosis, cell cycle, β-catenin, Bcl-2, Cyclin D1, Bax

DOI: 10.3233/CBM-182046

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 395-404, 2019

Authors: Globus, Tatiana | Moskaluk, Christopher | Pramoonjago, Patcharin | Gelmont, Boris | Moyer, Aaron | Bykhovski, Alexei | Ferrance, Jerome

Article Type: Research Article

Abstract: ABSTRACT: We introduce here recently developed highly resolved Sub-Terahertz resonance spectroscopy of biological molecules and cells combined with molecular dynamics (MD) computational analysis as a new approach for optical visualization and quantification of the presence of microRNAs, particularly the mir-200 family, as potential biomarkers in samples from tissue of epithelial ovarian cancers for disease early detection, analysis, prognosis and treatment. METHOD: A set of samples for this study was prepared from anonymized archival formalin-fixed, paraffin-embedded ovarian epithelial tissue containing regions of invasive neoplastic cells from cases of high-histologic grade serous papillary ovarian carcinoma. Control samples were …normal mucosa from fallopian tubes of patients with no known malignancy. Spectroscopic characterization of tissue samples in this study was performed using a continuous wave, frequency domain automated spectrometer operating at room temperature in the spectral region of 310–500 GHz. The spectral results were compared with molecular dynamics simulations and absorption coefficient calculations utilized to predict the absorption spectra. RESULTS: The characteristic spectroscopic features in absorption spectra, particularly the presence of absorption peaks near 13 cm - 1 have been identified as cancer indicators. Tissue samples heterogeneity, reflected by diverse spectral signatures, provides additional, very specific information that may be used for identification of cancer subtypes, clinical behavior or sensitivity to specific therapies. Further work is warranted to determine if this signature can be detected in bio-fluids from ovarian cancer patients. If strongly correlated with cancer burden, it may then be investigated as a potential new biomarker for disease monitoring, and also perhaps as a biomarker for cancer screening. Show more

Keywords: Optical, visualization, molecular, biomarkers, ovarian cancer tissue, subtypes

DOI: 10.3233/CBM-182120

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 405-419, 2019

Authors: Zeng, Saitian | Liu, Shikai | Feng, Jing | Gao, Jiefan | Xue, Fengxia

Article Type: Research Article

Abstract: BACKGROUNDS: Upregulation of lncRNA AB073614 is found in some cancer types and involved in tumor development and progression including ovarian cancer. However, the clinical value and functional role of lncRNA AB073614 in epithelial ovarian cancer (EOC) still needed to be investigated. METHODS: We examined lncRNA AB073614 expression using quantitative real time polymerase chain reaction (qRT-PCR) in 75 paired of EOC tissue samples and adjacent normal tissues. Association of lncRNA AB073614 expression with overall survival (OS) was evaluated using Kaplan-Meier analysis. Univariate and multivariate analysis of factors associated with OS were assessed in EOC patients. After lncRNA …AB073614 knockdown using siRNAs, the cell viability and cell colony forming assays were performed. Western blot analysis was used to assess relative protein expression. RESULTS: In present study, we demonstrated that lncRNA AB073614 was significantly upregulated in ovarian cancer tissues compared to adjacent normal tissues in patients. Higher lncRNA AB073614 expression significantly associated with tumor size, lymph node invasion, FIGO stage, and shorter OS rate of EOC patients. Furthermore, multivariate Cox regression analysis results showed that higher lncRNA AB0736141 was identified as an independent risk factor of OS in EOC patients. Moreover, we demonstrated that lncRNA AB0736141 knockdown suppressed EOC cell proliferation ability and cell colony formation in vitro . In vivo , we showed that AB0736141 knockdown suppressed tumor growth. We also revealed that lncRNA AB0736141 knockdown inhibited the PTEN/PI3K/AKT signaling pathway in EOC. CONCLUSIONS: Thus, these results indicated that LncRNA AB073614 may serve as a prognostic biomarker and potential target of treatment for EOC. Show more

Keywords: Epithelial ovarian cancer, AB0736141, tumor prognosis, cell proliferation, long non-coding RNA

DOI: 10.3233/CBM-182160

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 421-428, 2019

Authors: Zhang, Shuhua | Xu, Jianqun | Wang, Hongjuan | Guo, Hongrong

Article Type: Research Article

Abstract: BACKGROUND: Long noncoding RNA have been indicated to be involved in tumor development. However, the role of LINC00460 in gastric cancer (GC) still remains large unknown. The current study is designed aiming at determining the effects of LINC00460 on GC progression. PATIENTS AND METHODS: The expression of LINC00460 in GC tissues and cells were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The cell proliferation, cell cycle distribution and cell invasion were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry analysis and transwell cell invasion assays. Western blot analysis was used to detect the WNT signaling …related protein expression. Tumor xenograft assay was used to detect the effects of LINC00460 in vivo . RESULTS: In the study, we demonstrated that LINC00460 expression was higher in gastric cancer tissues compared to adjacent normal tissues. Higher LINC00460 expression associated with lymph node metastasis and advanced TNM stage. Furthermore, we showed that higher LINC00460 expression predicted a poor disease-free survival (DFS) and overall survival (OS) time of gastric cancer. Multivariate analysis showed that LINC00460 expression was an independent risk factor of GC prognosis. Furthermore, in vitro , we demonstrated that inhibition of LINC00460 expression suppressed cell proliferation, S phase cell number and cell invasion of gastric cancer cells compared to the control groups. In addition, we showed that downregulation of LINC00460 inhibited the Wnt/β -catenin signaling by downregulating c-Myc and β -catenin expression, which indicated LINC00460 could promote cell proliferation and invasion by activating Wnt/β -catenin signaling. In vivo , we also demonstrated that LINC00460 knockdown significantly suppressed cell proliferation. CONCLUSIONS: LINC00460 is a new type of molecule involved in the development of GC, which may become a potential target for the treatment of GC. Show more

Keywords: Gastric cancer, LINC00460, prognosis, cell proliferation, cell invasion

DOI: 10.3233/CBM-182177

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 429-437, 2019

Authors: Zhou, Xiao-Hui | Zhang, Xin-Yu | Liang, Jin-Hua | Zhu, Hua-Yuan | Wang, Li | Xia, Yi | Cao, Lei | Wu, Wei | Fan, Lei | Li, Jian-Yong | Xu, Wei

Article Type: Research Article

Abstract: BACKGROUND: Although risk stratification of mantle cell lymphoma (MCL) is most frequently performed using the simplified MCL International Prognostic Index (sMIPI), the identification of host-related factors and tumor microenvironment, including absolute monocyte counts (AMC) and peripheral blood T lymphocyte subsets, especially absolute natural killer cell counts (ANKC) has been suggested to be critical in the prediction of prognosis and the guidance of treatment. OBJECTIVE: This study was aimed at investigating whether peripheral blood ANKC and AMC at diagnosis had an impact on MCL prognosis. METHODS: A total of 92 newly diagnosed MCL patients …was enrolled in this retrospective study. Flow cytometric analysis was conducted on fresh peripheral blood samples with a FACSCalibur flow cytometer (BD Biosciences, San Jose, CA, USA). RESULTS: The median follow-up was 42 months (range, 2–144 months) and the median overall survival (OS) of all cases was 45 months. High AMC (> 0.6 × 10 9 /L) was the parameter associated with inferior progression free survival (PFS) (P = 0.044) and poor OS (P = 0.028) while low ANKC (⩽ 0.1 × 10 9 /L) was associated with unfavorable OS (P = 0.023) by univariable analysis. Multivariable analysis revealed that only low ANKC (⩽ 0.1 × 10 9 /L) was statistically significant in worse OS (P = 0.009) independent of sMIPI. CONCLUSIONS: Low ANKC (⩽ 0.1 × 10 9 /L) proved to be a significant predictor of inferior OS in patients with MCL. Show more

Keywords: Mantle cell lymphoma, absolute natural killer cell counts, absolute monocyte counts, prognosis

DOI: 10.3233/CBM-182193

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 439-447, 2019

Authors: Chen, Xi | Xu, Zhijie | Zeng, Shuangshuang | Wang, Xiang | Liu, Wanli | Qian, Long | Wei, Jie | Yang, Xue | Shen, Qiuying | Gong, Zhicheng | Yan, Yuanliang

Article Type: Research Article

Abstract: OBJECTIVE: Sirtuins (SIRT) are NAD + -dependent protein deacetylases that are involved in the regulation of cancer-associated pathways. However, the biological role of these deacetylases remains elusive in glioblastoma (GBM). Here, we evaluated the effects of 7 sirtuins regarding their occurrence and prognostic value for GBM. METHODS: In this research, the effects of SIRT5 on the occurrence and prognosis of GBM were evaluated using integrative bioinformatics analyses. RESULTS: Based on comprehensive analyses of data obtained from web-based bioinformatics platforms, the data demonstrate that only SIRT5 expression is statistically decreased in …GBM tissues. The clinical relevance analysis shows that downregulation of SIRT5 is significantly correlated with a shorter survival time. Moreover, the expression levels of SIRT5 were confirmed to be negatively associated with DNA methylation status. In addition, a protein-protein interaction network was constructed to determine the relationship of genes coexpressed with SIRT5. Functional enrichment analysis revealed that SIRT5 was potentially involved in epithelial-mesenchymal transition and in regulating cell communications. CONCLUSIONS: Collectively, our results indicate that SIRT5 acts as a potential suppresser during tumorigenesis, and suggest that SIRT5 may be a promising prognostic biomarker of GBM. Show more

Keywords: Glioblastoma, SIRT5, prognosis, overall survival, DNA methylation

DOI: 10.3233/CBM-182197

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 449-459, 2019

Authors: Wang, Gang | Fu, Shan | Li, Dechuan | Chen, Yinbo

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to investigate the expression level and clinical significance of serum NT5E protein (ecto-5’-nucleotidase) in patients with colorectal cancer. METHODS: The expression level of serum NT5E protein in 232 patients with colorectal cancer and 158 normal controls was detected using enzyme-linked immunosorbent assay. Moreover, the relationship between the expression level of serum NT5E and the clinicopathological features of colorectal cancer was analyzed. RESULTS: The expression level of serum NT5E in patients with colorectal cancer was significantly higher compared with that in normal controls (P < …0.05). The expression level of serum NT5E in patients with colorectal cancer closely correlated with the family history of tumors (P = 0.001), expression level of CA19-9 (P = 0.031), lymph node metastasis (P = 0.001), distant metastasis (P = 0.010), nerve invasion (P = 0.049), degree of differentiation (P = 0.013), and TNM staging (P = 0.001), but not with gender, age, smoking and drinking histories, expression level of carcinoembryonic antigen (CEA), tumor locations, vascular tumor thrombus, cancer nodules, and pathological type (P > 0.05). Moreover, the overall survival rate of patients with colorectal cancer was significantly lower in the NT5E high-expression group, with statistical significance (χ 2 = 11.184, P = 0.001). CONCLUSIONS: The expression level of serum NT5E increased in patients with colorectal cancer, and closely correlated with the malignant evolution and clinical prognosis of colorectal cancer. NT5E might serve as a serological indicator for molecular diagnosis and prognosis of colorectal cancer clinically. Show more

Keywords: NT5E, colorectal cancer, prognosis

DOI: 10.3233/CBM-182207

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 461-468, 2019

Authors: Qin, Yujing | Li, Wenxue | Long, Yingli | Zhan, Zhijia

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to determine the correlation between p-cofilin expression and cisplatin resistance in patients with ovarian cancer, and also to investigate the role of p-cofilin in prognosis. PATIENTS AND METHODS: The ovarian cancer cell line A2780/DDP resistant to cisplatin was prepared. The cell resistance to cisplatin was measured via MTT assay. The cell invasion capacity was identified via Transwell assay. The mRNA expression and protein level was evaluated via semi-quantitative PCR and Western blot, respectively. The tumor tissues of patients with cisplatin-resistant ovarian cancer were collected. The relationship between prognosis and p-cofilin expression was …analyzed. RESULTS: The growth rate of A2780 was similar to that of A2780/DDP. The sensitivity of A2780 to cisplatin was significantly higher than that of A2780/DDP (p < 0.01). The migration capacity of A2780/DDP was significantly increased compared to that of A2780 (p < 0.01), indicating that the cisplatin-resistant cell lines were successfully constructed. Both CFL1 mRNA level and p-cofilin level in A2780/DDP was significantly higher than that in A2780 (p < 0.01). The p-cofilin level in cancer tissues in patients with cisplatin-resistant ovarian cancer was significantly higher than that in patients with cisplatin-sensitive ovarian cancer (p < 0.01). The cisplatin resistance was positively correlated with the p-cofilin expression level (r = 0.802, p = 0.023). The survival time of patients with normal or low level of p-cofilin was significantly longer than that of patients with high expression. CONCLUSION: The cisplatin resistance of ovarian cancer is closely related to the expression level of p-cofilin, which affects the prognosis of patients with ovarian cancer. Show more

Keywords: Ovarian cancer, p-cofilin, drug resistance

DOI: 10.3233/CBM-182209

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 469-475, 2019

Authors: Kong, Ying | Ning, Liang | Qiu, Fei | Yu, Qian | Cao, Bin

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: MicroRNAs (miRNAs) are under investigation as novel diagnostic and prognostic biomarkers in several malignancies, including gastric cancer (GC). miR-25 was overexpressed in GC tissues, and higher miR-25 expression was statistically correlated with aggressive clinicopathological characteristics. In our study, we investigate the associations of serum miR-25 level with the clinicopathological characteristics, diagnosis and prognosis of GC patients. METHODS: Serum samples from 184 GC patients, 56 gastritis patients and 78 healthy controls were subjected to real-time quantitative polymerase chain reaction (RT-qPCR), and the relationship between micR-25 level and cliniopathological characteristics including diagnosis and prognosis was …explored. RESULTS: Compared with the gastritis and healthy patients, serum miR-25 level was significantly up-regulated in patients with GC. Using a cut-off of 0.042, the level of miR-25 was significantly increased in serum samples from cancer patients; Using this test cancer patients were identified with 67.3–69.4% sensitivity and 80.4%–81.0% specificity. High serum miR-25 level was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univariate and multivariate analyses, miR-25 was an independent prognostic factor for overall survival (OS). Moreover, high serum miR-25 level was correlated with poor prognosis in patients subgroups stratified by tumor size, depth of invasion and lymph node metastasis. Serum miR-25 level was increased in both prominent serosal invasion group and lymph node metastasis group. Furthermore, stratified analysis showed that the TNM stage I–VI patients with high serum miR-25 level had poor prognosis than those with low serum miR-25 level. CONCLUSIONS: Serum levels of miR-25 could improve gastric cancer screening, and as the better diagnostic and prognostic marker of gastric cancer. Show more

Keywords: Gastric cancer, miR-25, prognosos, diagnosis

DOI: 10.3233/CBM-182213

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 477-483, 2019

Authors: Jeong, Dongjun | Kim, Hyeongjoo | Kim, Doyeon | Ban, Seona | Oh, Seunghyun | Ji, Sanghee | Kang, DongHyun | Lee, Hyunyong | Ahn, Tae Sung | Kim, Han Jo | Bae, Sang Byung | Lee, Moon Soo | Kim, Chang-Jin | Kwon, Hyog Young | Baek, Moo-Jun

Article Type: Research Article

Abstract: Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo . Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro . Furthermore, DEFA6-deficient cancer …cells exhibited significantly reduced growth rates compared to control cells in vivo . More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease. Show more

Keywords: DEFA6, CRC, tumorigenesis

DOI: 10.3233/CBM-182221

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 485-495, 2019

Authors: Ding, Qiuli | Li, Xiaoyan | Sun, Yongcun | Zhang, Xinru

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM-229008.

Keywords: Schizandrin A, thyroid cancer, miR-429, Wnt/β-catenin, MEK/ERK

DOI: 10.3233/CBM-182222

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 497-508, 2019

Authors: Fang, Jiyang | Huang, Jianyue

Article Type: Research Article

Abstract: BACKGROUND: Glioma is the most common primary malignant tumor in the nervous system. OBJECTIVE: To investigate the expression of long non-coding RNA Pvt1 oncogene (PVT1) in glioma and its clinical significance. METHODS: The expression levels of PVT1 were determined in 59 glioma and 10 normal tissue samples using qRT-PCR. The patients were divided into high and low expression groups and analyzed for their relationship with clinicopathological factors and the survival time using the Kaplan-Meier method. RESULTS: The expression levels of PVT1 were significantly higher in glioma tissues than in normal …tissues (p < 0.01) and higher in high grade (III–IV) than in low grade (I–II) tumors (p < 0.01). Analysis showed that the PVT1 level was closely related to glioma grade (p < 0.01), but not to age, gender, Karnofsky performance status (KPS) and tumor size (p > 0.05). Receiver operator characteristic curve analysis showed an area under the curve of 0.835. Log-rank test showed that the prognosis of high PVT1 group was poorer than that of low PVT1 group (p < 0.01). CONCLUSIONS: PVT1 is highly expressed in gliomas and its level is positively related to WHO glioma grade and prognosis of gliomas. Therefore, it may be explored as a new molecular marker for predicting malignancy and prognosis of gliomas. Show more

Keywords: Glioma, long non-coding RNA, plasmacytoma variant translocation gene 1, prognosis

DOI: 10.3233/CBM-182253

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 509-513, 2019

Authors: Li, Ming-Ming | Wang, Xin | Yun, Zhi-Yuan | Wang, Rui-Tao | Yu, Kai-Jiang

Article Type: Research Article

Abstract: BACKGROUND: Platelets play a crucial role in cancer progression and metastasis. The aim of the present study was to assess the relationship between platelet indices and non-small cell lung cancer (NSCLC) with brain metastases. METHODS: Between January 2015 and December 2017, 232 NSCLC patients with brain metastases and 244 NSCLC patients without metastases were retrospectively analyzed. Patients’ clinicopathological characteristics data were collected. RESULTS: Platelet count was increased and mean platelet volume (MPV) was reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. In addition, the prevalence of NSCLC decreased …as MPV quartiles increased. After adjusting for other risk factors, the ORs (95% CIs) for NSCLC brain metastases according to MPV quartiles were 1.757 (1.024–3.015), 2.097 (1.209–3.635), 1.517 (0.874–2.635), and 1.000, respectively. CONCLUSIONS: MPV is reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. Moreover, MPV is found to be independently associated with the presence of NSCLC brain metastases. Show more

Keywords: Non-small cell lung cancer, mean platelet volume, platelet activation

DOI: 10.3233/CBM-192393

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 515-519, 2019

Article Type: Other

DOI: 10.3233/CBM-179556

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 521-, 2019

Article Type: Other

DOI: 10.3233/CBM-189863

Citation: Cancer Biomarkers, vol. 24, no. 4, pp. 523-, 2019