Cancer Biomarkers - Volume 22, issue 1

Authors: Chen, Qi | Zhang, Hong

Article Type: Research Article

Abstract: Ovarian cancer has the highest mortality rate among gynecological malignancies, presenting a major threat to women’s life and health. It is essential to study the mechanisms of drug resistance to chemotherapy to identify ways to enhance drug-sensitivity. In recent years, many studies have shown that Smac/DIABLO is closely related to tumor drug resistance. Smac/DIABLO expression is markedly different between drug-resistant and chemo sensitive tumor cells. Up-regulation of Smac/DIABLO has been shown to increase tumor cell chemotherapy sensitivity. We found that Smac, combined with DDP greatly inhibited proliferation of subcutaneous xenografts of ovarian cancer cell line SKOV3/DDP without side effects. Mechanistic …studies showed that Smac can inhibit the expression of Survivin, promote cell apoptosis of drug-resistant ovarian cancer cells and reverse the drug resistance. Show more

Keywords: Smac, DDP, drug-resistant, ovarian cancer cell, Survivin

DOI: 10.3233/CBM-170325

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 1-6, 2018

Authors: Wang, Xu | Zhang, Xiaochang | Jin, Lina | Yang, Zhiguang | Li, Wei | Cui, Jiuwei

Article Type: Research Article

Abstract: OBJECTIVE: Early detection and diagnosis of lung cancer remain challenging but would improve patient prognosis. The goal of this study is to develop a model to estimate the risk of lung cancer for a given individual. METHODS: We conducted a case-control study to develop a predictive model to identify individuals at high risk for lung cancer. Clinical data from 500 lung cancer patients and 500 population-based age- and gender-matched controls were used to develop and evaluate the model. Associations between environmental variants together with single nucleotide polymorphisms (SNPs) of beta-catenin (ctnnb1 ) and lung cancer risk were analyzed …using a logistic regression model. The predictive accuracy of the model was determined by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Prior diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis, family history of cancer, and smoking are lung cancer risk factors. The area under the curve (AUC) was 0.740, and the sensitivity, specificity, and Youden index were 0.718, 0.660, and 0.378, respectively. CONCLUSION: Our risk prediction model for lung cancer is useful for distinguishing high-risk individuals. Show more

Keywords: ctnnb1, single nucleotide polymorphism, risk prediction model, lung cancer, Chinese population

DOI: 10.3233/CBM-170563

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 7-12, 2018

Authors: Su, Guangfeng | Chen, Hao | Sun, Xinhua

Article Type: Research Article

Abstract: BACKGROUND: Baicalein is an important Chinese herbal medicine and has multiple pharmacological activities. However, the biological mechanisms of the anti-tumor effects of Baicalein on non small cell lung cancer (NSCLC) still need to be understood. METHODS: Human NSCLC A549 and H1299 cells were pretreated with Baicalein or DMSO. Cells viability and transwell cell invasion assays were performed to assess cell proliferation and invasion. QRT-PCR assay was used to analyze mRNA expression levels of Twist1, E-cadhertin, Vimentin, Notch1 and hes-1. Western blot analysis was also performed to determine protein expression. RESULTS: In the study, …we found that Baicalein had a significantly inhibited effect on proliferation ability of A549 and H1299 cells. Cells treated with Baicalein showed a down-regulated expression of CyclinD1 and CDK1 in A549 and H1299 cells. Furthermore, we found that Baicalein significantly inhibited cell invasion and Epithelial-Mesenchymal Transition (EMT) by up-regulating the mRNA and protein expression of E-cadherin and down-regulated the Twist1 and Vimentin expression, Moreover, Treatment of Baicalein down-regulated Notch1 and hes-1 expression in A549 and H1299 cells, which indicated that Baicalein could suppress the Notch signaling pathway. CONCLUSION: Our studies suggest that Baicalein may be a potential phytochemical flavonoid for therapeutics of NSCLC and serve as a molecular target for NSCLC. Show more

Keywords: Baicalein, non small cell lung cancer, cell proliferation, epithelial-mesenchymal transition

DOI: 10.3233/CBM-170673

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 13-18, 2018

Authors: Khorasani, Maryam | Teimoori-Toolabi, Ladan | Farivar, Taghi Naserpour | Asgari, Mojgan | Abolhasani, Maryam | Shahrokh, Hossein | Afgar, Ali | Kalantari, Elham | Peymani, Amir | Mahdian, Reza

Article Type: Research Article

Abstract: BACKGROUND: Prostate cancer (PCa) is the second most common cancer in men worldwide. Currently, prostate-specific antigen (PSA) test and digital rectal exam are the main screening tests used for PCa diagnosis. However, due to the low specificity of these tests, new alternative biomarkers such as deregulated RNAs and microRNAs have been implemented. OBJECTIVES: Aberrant expressions of small heterodimer partner gene (SHP, NR0B2 ) and mir-141 are reported in various cancers. The aim of this study was to investigate the SHP and miR-141 expression level in tissue samples of prostate cancer. METHODS: The …expression level of SHP gene and miR-141 was assessed by real time PCR and their relative amounts were calculated by the Δ ⁢ Δ CT method. Also, IHC technique was used to determine the expression level of SHP protein. RESULTS: The miR-141 was significantly up-regulated in the samples of metastatic tumors compared to localized tumor samples (P < 0.001, 31.17-fold change). Tumor samples showed lower SHP mRNA expression levels than BPH samples (p = 0.014, 4.7-fold change). The results of paired t -test analysis showed there was no significant difference between the SHP gene expression in PCa samples and their matched tumor-adjacent normal tissue (p = 0.5). CONCLUSIONS: The data obtained in our study confirm the involvement of miR-141 in PCa progression and metastasis. These effects could be mediated by AR via down-regulation of its co-repressor protein, i.e., SHP . Show more

Keywords: Prostate cancer, SHP gene, miR-141, biomarker, nuclear receptors, gene expression, Immunohistochemistry

DOI: 10.3233/CBM-170696

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 19-28, 2018

Authors: Duan, Guoqing | Hou, Su | Ji, Jianjun | Deng, Bin

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

Keywords: Sclareol, cell apoptosis, mitochondrial membrane potential, osteosarcoma cells

DOI: 10.3233/CBM-170698

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 29-34, 2018

Authors: Choi, Kyu Young | Kim, Jin Hwan | Park, Il Seok | Rho, Young Soo | Kwon, Gee Hwan | Lee, Dong Jin

Article Type: Research Article

Abstract: BACKGROUND: Cervical lymph node metastases (LNM) in papillary thyroid carcinomas (PTCs) are common and develop in approximately 30–80% of PTCs. The presence of cervical LNM significantly increases the rate of locoregional recurrence in PTCs. OBJECTIVE: To search for predictive gene signatures for nodal metastasis in PTCs. METHODS: We used unsupervised clustering with unbiased manner to compare molecular profiles between PTCs with nodal metastasis and PTCs without nodal metastasis using mRNA-seq of TCGA data. Using gene ontology (GO) and logistic regression test, we generated 12-predictive genes for nodal metastasis in PTCs. RESULTS: …Unsupervised clustering of mRNA-seq (training set, N = 158) revealed that PTCs with nodal metastasis showed different gene expression patterns compared to PTCs without nodal metastasis. We generated 12 predictive genes and these gene signatures showed consistency for predicting nodal metastasis when we applied them to a validation set (N = 80). Based on multivariate analysis, these 12 predictive gene signatures showed more significant odds ratio compared to other variables. CONCLUSIONS: These 12 gene signatures could be used to predict the chance of nodal metastasis in PTCs in preoperative evaluation using fine needle aspiration biopsy (FNAB) so that appropriate plan such as central neck dissection could be made. Show more

Keywords: Gene expression, PTC, node metastasis, prediction, gene signature

DOI: 10.3233/CBM-170784

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 35-42, 2018

Authors: Zhou, Xin | Wang, Jing | Xia, Jun | Cheng, Feng | Mao, Jingjue | Zhu, Jianwei | Guo, Hongfeng

Article Type: Research Article

Abstract: BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. OBJECTIVE: We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. METHODS: A total of 76 newly diagnosed patients with MM treated with bortezomib-based …regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. RESULTS: Complete remission (CR) was seen in 39.2% of patients with NLR < 2.95 compared to 20% in the group with NLR ⩾ 2.95 (P = 0.094). NLR was lower in CR patients in comparison to Non-CR subjects (P = 0.044). Patients with a NLR ⩾ 2.95 experienced inferior median survival compared to those with NLR < 2.95 (4-year OS rates were 30.9% and 64.8%, respectively, P = 0.029). In multivariate analysis, only elevated LDH and IgA MM were factors predicting inferior OS. CONCLUSIONS: Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort. Show more

Keywords: Bortezomib, multiple myeloma, neutrophil-to-lymphocyte ratio, prognostic

DOI: 10.3233/CBM-170795

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 43-48, 2018

Authors: Dianatpour, Ali | Faramarzi, Sepideh | Geranpayeh, Lobat | Mirfakhraie, Reza | Motevaseli, Elahe | Ghafouri-Fard, Soudeh

Article Type: Research Article

Abstract: Long non-coding RNAs (lncRNA) constitute a significant percentage of RNAs with no translation to proteins. Their participation in fundamental aspects of cell physiology as well as their dysregulation in a number of pathologic conditions such as cancer have been documented. Among lncRNAs is actin filament associated protein 1 antisense RNA1 (AFAP1-AS1 ) whose elevated expression levels have been demonstrated in different cancers. In the in the present study we evaluated expression levels of AFAP1-AS1 and its antisense protein coding gene AFAP1 in breast cancer samples compare with adjacent non-cancerous tissues (ANCTs) as well as breast cancer cell …lines with special focus on the assessment of the association between their transcript levels and patients’ clinicopathological data. AFAP1-AS1 has shown significant up-regulation in both MDA-MB-231 and MCF-7 compared with control sample. AFAP1-AS1 has been shown to be expressed in all of tumor tissues but 76% (39 out of 51) ANCTs. AFAP1 expression was not significantly different between tumor samples and ANCTs. AFAP1-AS1 has been demonstrated to be significantly up-regulated in tumor tissues compared with ANCTs (fold change = 4.65, P = 0.028). No significant correlation has been detected between the levels of these two transcripts in tumor tissues (R= 2 0.081) or ANCTs (R= 2 0.115). No significant associations have been found between expression levels of these genes and patients’ characteristics. However, both genes were significantly down-regulated in Ki-67 negative tumor samples. The observed up-regulation of AFAP1-AS1 in tumor samples compared with ANCTs implies its involvement in breast cancer pathogenesis and potentiates it as a biomarker or therapeutic target. Show more

Keywords: lncRNA, AFAP1-AS1, AFAP1, breast cancer

DOI: 10.3233/CBM-170831

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 49-54, 2018

Authors: Baek, Ae Rin | Seo, Hyun Jung | Lee, June Hyuk | Park, Sung Woo | Jang, An Soo | Paik, Sang Hyun | Koh, Eun Suk | Shin, Hwa Kyun | Kim, Do Jin

Article Type: Research Article

Abstract: BACKGROUND: Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels are prognostic predictors in non-small cell lung cancer (NSCLC). However, even in patients with the same stage of cancer, the serum levels of those markers often vary. OBJECTIVE: We investigated the association between the initial biomarker levels and prognosis. METHODS: We retrospectively reviewed 445 patients with advanced NSCLC and their baseline serum CEA and CYFRA 21-1 levels. Patients were divided into four groups according to the initial levels of those markers: the NN, HN, NH, and HH group. Kaplan-Meier survival analysis …with Log-rank test and Cox proportional hazards regression analysis were performed. RESULTS: The 5-year overall survival (OS) rate in the HN group was the highest (32.2%). Multivariate analyses indicated that the HN group (HR 0.520, 95% CI 0.309–0.878, P = 0.014), female sex (HR 0.685, 95% CI 0.498–0.944, P = 0.021), serum CRP level (HR 1.057, 95% CI 1.034–1.080, P < 0.001), chemotherapy (HR 0.324, 95% CI 0.228–0.460, P < 0.001), and chemotherapy/radiotherapy (HR 0.266, 95% CI 0.171–0.414, P < 0.001) were independent prognostic factors for overall survival. CONCLUSIONS: In advanced NSCLC, patients with baseline high serum CEA but low CYFRA 21-1 level have a significant longer overall survival regardless of clinical stage. Show more

Keywords: CEA, CYFRA 21-1, tumor marker, prognostic factor, NSCLC

DOI: 10.3233/CBM-170885

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 55-62, 2018

Authors: Ma, Jun | Wu, Kaiming | Liu, Kuanzhi | Miao, Rong

Article Type: Research Article

Abstract: OBJECTIVE: To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. METHODS: LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting. The CCK8 assay was performed for cell proliferation, the scratch test for cell migration, the Transwell assay …for cell invasion, and the flow cytometry for cell cycle and apoptosis. Tumor xenograft in nude mice is performed to test tumorigenesis of the transfected A549 cells. RESULTS: The expression level of MALAT-1 in A549, SPC-A-1 and NCI-H460 cells was increased compared to HBE cells. And A549 with a high expression level of MALAT-1 were selected for cell transfection. si-MALAT-1 decreased cell proliferation, migration, invasion, and LC3-II/LC3-I ratio, reduced cell cycle progression, and increased cell apoptosis and P62 protein expression. No significant difference was found between A549 cells and A549 cells transfected with si-MALAT-1 + RAPA, A549 cells transfected with NC and A549 cells transfected with si-MALAT-1 + RAPA. Nude mice injected with A549 cells transfected with si-MALAT-1 had smallest tumor on size and weight among other nude mice. CONCLUSION: Downregulation of MALAT1 may promote apoptosis and suppress proliferation, migration and invasion of human NSCLC A549 cells by inhibiting autophagy, thereby suppressing the development of NSCLC. Show more

Keywords: Non-small cell lung cancer, MALAT-1, A549, autophagy, proliferation, apoptosis, migration, invasion

DOI: 10.3233/CBM-170917

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 63-72, 2018