Cancer Biomarkers - Volume 16, issue 3

Authors: Petrović, Nina | Kolaković, Ana | Stanković, Aleksandra | Lukić, Silvana | Řami, Ahmad | ivković, Maja | Mandušić, Vesna

Article Type: Research Article

Abstract: BACKGROUND: Breast carcinoma is heterogeneous disease. Understanding the process of invasion and metastasis and the selection of the therapy for patients with breast carcinomas still remains difficult. MicroRNAs are powerful gene expression regulators. Because of inconsistent findings, we have analyzed potential difference in miR-155 levels in three breast cancer groups. OBJECTIVES: Our goals were to examine miR-155 expression levels in normal tissue, non-invasive and invasive breast carcinomas, and their association with standard clinical and pathological parameters and oncomiR-21, and to investigate the ability of miR-155 to separate invasive breast carcinomas with non-invasive component from pure invasive. …METHODS: In the group of 40 breast tissue samples, relative expression levels of miR-155 were examined with stem-loop quantitative real-time PCR using TaqMan technology. RESULTS: The significant difference among four examined groups of the breast tissue was detected (p = 0.001). In the group of pure invasive tumors, patients with positive nodal status had significantly higher miR-155 levels (p = 0.046). CONCLUSION: Our results suggest that miR-155 might be involved in breast cancer pathogenesis and in tumor spreading to the lymph nodes, and that it might be used as biomarker for additional stratification of patients with invasive breast carcinomas with non-invasive component. Show more

Keywords: miR-155, , breast cancer, , microRNA expression levels

DOI: 10.3233/CBM-160577

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 385-394, 2016

Authors: Gu, Xi | Xue, Jin-Qi | Han, Si-Jia | Qian, Song-Ying | Zhang, Wen-Hai

Article Type: Research Article

Abstract: OBJECTIVE: We aimed to explore the potential application of circulating microRNA-451 (miR-451) in serum in predicting the resistance to neoadjuvant chemotherapy (NACT) in breast cancer (BC). METHODS: Eighty-two BC patients who underwent NACT were recruited in our study, including 41 NACT-sensitive patients (NACT-sensitive group) and 41 NACT-resistant patients (NACT-resistant group). Additionally, 60 healthy subjects were selected as normal controls. Epirubicin-resistant MCF-7 BC cell line (MCF-7/EPI) and docetaxel-resistant MCF-7 BC cell line (MCF-7/DOC) were cultured in our study. MTT assay was applied to calculate the survival rates of MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells. The expression …levels of miR-451 in normal controls, NACT-sensitive group, NACT-resistant group, MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells were measured by qRT-PCR method. RESULTS: The proliferation rates of both the MCF-7/DOC and MCF-7/EPI cells were significantly restrained at the drug concentration of 10 ng/ml, 50 ng/ml, 100 ng/ml and 200 ng/ml. However, the proliferation rates of MCF-7/DOC and MCF-7/EPI cells both increased significantly at the drug concentration of 500ng/ml. Furthermore, the IC50 of MCF-7/DOC cells was 23.603 ng/ml and the IC50 of MCF-7/EPI cells was 3.209 ng/ml. The relative expression of miR-451 was significantly lower in both the NACT-resistant group and the NACT-sensitive group than the normal control group. We also found that the relative expression level of miR-451 was significantly lower in the NACT-resistant group than that in the NACT-sensitive group. The expression of miR-451 in the MCF-7/EPI and the MCF-7/DOC cell lines was significantly lower than that in the MCF-7 cell lines. CONCLUSION: We supported the view that the relative expression level of miR-451 was lower in the NACT-resistant BC patients, suggesting the circulating miR-451 may have a functional significance in predicting the resistance to NACT in BC patients. We laid a foundation for further research on the resistance to NACT in BC treatment. Show more

Keywords: Breast cancer, microRNA-451, neoadjuvant chemotherapy, drug tolerance, circulating serum level, epirubicin-resistant MCF-7 cell line, docetaxel-resistant MCF-7 cell line

DOI: 10.3233/CBM-160578

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 395-403, 2016

Authors: Xie, Bin-Hui | He, Xiao | Hua, Rui-Xi | Zhang, Bing | Tan, Guo-Sheng | Xiong, Shi-Qiu | Liu, Liang-Shuai | Chen, Wei | Yang, Jian-Yong | Wang, Xiao-Nong | Li, He-Ping

Article Type: Research Article

Abstract: microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively. Overexpression of mir-765 increased HCC cells proliferation and tumorigenicity, whereas inhibition of mir-765 reverses this effect. Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 …repressed INPP4B expression, resulting in upregulation of p-AKT, Cyclin D1, and downregulation of p-FOXO3a, p21 expression in HCC. Strikingly, we found that silencing the expression of INPP4B is the essential biological function of miR-765 during HCC cell proliferation. Collectively, our findings reveal that miR-765 is a potential onco-miR that participates in carcinogenesis of human HCC by suppressing INPP4B expression, and might represent a potential therapeutic target for HCC patients. Show more

Keywords: miR-765, INPP4B, proliferation, human hepatocellular carcinoma

DOI: 10.3233/CBM-160579

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 405-413, 2016

Authors: Zhang, Xiuxiu | Guo, Mengfei | Fan, Jinshuo | Lv, Zhilei | Huang, Qi | Han, Jieli | Wu, Feng | Hu, Guorong | Xu, Juanjuan | Jin, Yang

Article Type: Research Article

Abstract: BACKGROUND: Lactare dehydrogenase (LDH) has been proven to be a prognostic and a potential pro-tumor factor in patients with lung cancer. But the prognostic value of serum LDH in small cell lung cancer (SCLC) has not been quantified systematically. OBJECTIVE: Thus, this study was to evaluate the correlations between serum LDH and overall survival of SLCLC by systematic review with meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science databases were searched from inception to October 2014 and references in those publications would be included if the association between serum LDH and overall …survival of SCLC can be derived. Quality assessment and data extraction were performed in the articles selected according to inclusion and exclusion criteria. RESULTS: Twenty-eight studies including 4785 patients with SCLC were deemed eligible. Pooled results showed that SCLC patients with elevated LDH levels were associated with an increased hazard ratio (HR 1.45, 95%CI 1.27∼ 1.66) of overall survival. CONCLUSIONS: The study suggests significant correlations between elevated serum LDH levels and poor overall survival in patients with SCLC. And serum LDH levels can be measured combining with other tools for assessing the risk stratification and prognosis of SCLC, which shows directions for treatments of SCLC. Show more

Keywords: Serum LDH levels, small cell lung cancer, prognosis, meta-analysis

DOI: 10.3233/CBM-160580

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 415-423, 2016

Authors: Park, Sehhoon | Park, Seongyeol | Lee, Se-Hoon | Suh, Beomseok | Ock, Chan-Young | Keam, Bhumsuk | Kim, Tae Min | Kim, Dong-Wan | Kim, Young Whan | Heo, Dae Seog

Article Type: Research Article

Abstract: BACKGROUND: A low albumin-to-globulin ratio (AGR) has been known as a prognostic factor for cancer-related mortality. However, no study has elucidated its usefulness as a predictive factor in the era of targeted therapy, and so, we evaluated this in the present study. METHODS: We retrospectively analyzed 2012 non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Among these patients, 645 patients who had EGFR mutation and suitable pretreatment laboratory values were included. AGR was calculated 2 months before treatment and 4 months after treatment in each patient. …The optimal cutoff value of AGR, and progression free survival (PFS) were also determined. RESULTS: The optimal cutoff value of AGR was 1.17, which yielded a highest HR of 1.89 (P< 0.001) for poor PFS. The median PFS was 9.5 months (95% confidential interval [CI] 7.0-10.4) in patients with pretreatment AGR < 1.17 and 13.5 months (95% CI 11.9-14.7) in those with pretreatment AGR ≥ 1.17. Pretreatment AGR showed an independent predictive value (adjusted HR 1.80, P < 0.001) when age, performance status, and pre-TKI systemic treatment was adjusted for. CONCLUSIONS: We suggest that patients with NSCLC with EGFR mutations who have AGR values lower than 1.17 at the beginning of EGFR TKI treatment should be considered to have a high risk of early EGFR TKI failure. Show more

Keywords: Albumins, globulins, non-small-cell lung carcinoma, tyrosine kinases inhibitor, epidermal growth factor receptor, disease-free survival

DOI: 10.3233/CBM-160581

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 425-433, 2016

Authors: Li, Ri-Heng | Zhang, Ai-Min | Li, Shuang | Li, Tian-Yang | Wang, Lian-Jing | Zhang, Hao-Ran | Li, Ping | Jia, Xiong-Jie | Zhang, Tao | Peng, Xin-Yu | Liu, Min-Di | Wang, Xu | Lang, Yan | Xue, Wei-Lan | Liu, Jing | Wang, Yan-Yan

Article Type: Research Article

Abstract: BACKGROUND: Rectal cancer is an important contributor to cancer mortality. OBJECTIVE: The objective of this paper is to identify key genes across three phenotypes (fungating, polypoid and polypoid & small-ulcer) of rectal cancer based on multiple differential expression networks (DENs). METHODS: Differential interactions and non-differential interactions were evaluated according to Spearman correlation coefficient (SCC) algorithm, and were selected to construct DENs. Topological analysis was performed for exploring hub genes in largest components of DENs. Key genes were denoted as intersections between nodes of DENs and rectal cancer associated genes from Genecards. …Finally, we utilized hub genes to classify phenotypes of rectal cancer on the basis of support vector machines (SVM) methodology. RESULTS: We obtained 19 hub genes and total 12 common key genes of three largest components of DENs, and EGFR was the common element. The SVM results revealed that hub genes could classify phenotypes, and validated feasibility of DEN methods. CONCLUSIONS: We have successfully identified significant genes (such as EGFR and UBC ) across fungating, polypoid and polypoid & small-ulcer phenotype of rectal cancer. They might be potential biomarkers for classification, detection and therapy of this cancer. Show more

Keywords: Rectal cancer, differential interactions, non-differential interactions, differential expression network, genes

DOI: 10.3233/CBM-160582

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 435-444, 2016

Authors: Ni, Zhenhua | Chen, Qingge | Lai, Yiming | Wang, Ziyuan | Sun, Li | Luo, Xuming | Wang, Xiongbiao

Article Type: Research Article

Abstract: BACKGROUND: CLPTM1L (Cleft lip and palate transmembrane protein 1-like) has been previously shown to be overexpressed in lung cancer and is involved in regulating cisplatin sensitivity. In this study, we assessed the relationship between CLPTM1L expression and prognosis of lung cancer in patients and explored its role in regulating cell migration and invasion. METHODS: Immunohistochemistry was used to examine CLPTM1L expression levels on a tissue microarray containing 73 sets of human lung cancer specimens with adjacent normal tissue. The correlation between CLPTM1L expression and patient survival was analysed by the Kaplan-Meier method. In addition, CLPTM1L-knockdown lung …cells were used to investigate the effect of CLPTM1L on cell migration and invasion in vitro . RESULTS: The results of immunohistochemical analysis showed that CLPTM1L was overexpressed in lung cancer tissues compared with adjacent normal tissues. Kaplan-Meier analyses revealed that patients with high CLPTM1L expression showed poorer survival than those with low CLPTM1L expression. In addition, in vitro studies revealed that the knockdown of CLPTM1L expression in 95-D lung cancer cells suppressed cell migration and invasion. Further, the loss of CLPTM1L resulted in decreased matrix metalloproteinase-2 (MMP-2) expression in these cells. CONCLUSION: Our data demonstrate that CLPTM1L overexpression can predict poor prognosis in patients with lung cancer and suggest that CLPTM1L might be associated with the regulation of cell migration and invasion. Show more

Keywords: Lung cancer, CLPTM1L, prognosis, migration, invasion

DOI: 10.3233/CBM-160583

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 445-452, 2016

Authors: Asanuma, Kunihiro | Matsumine, Akihiko | Nakamura, Tomoki | Matsubara, Takao | Asanuma, Yumiko | Oi, Toru | Goto, Mikinobu | Okuno, Kazuma | Kakimoto, Takuya | Yada, Yuuki | Sudo, Akihiro

Article Type: Research Article

Abstract: BACKGROUND: Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. OBJECTIVES: The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. METHODS: The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before …biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. RESULTS: According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). CONCLUSIONS: We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools. Show more

Keywords: Fibrinogen, soft tissue tumor, malignant, sarcoma, logistic analysis, receiver operating characteristic (ROC)

DOI: 10.3233/CBM-160584

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 453-458, 2016

Authors: Wang, Guanghui | Shen, Wei | Cui, Long | Chen, Wei | Hu, Xuguang | Fu, Jihong

Article Type: Research Article

Abstract: BACKGROUND: Our previous study found ANLN was over-expressed in colorectal cancer(CRC), however the role of ANLN in CRC remained unknown. OBJECTIVE: To investigate the relationship of ANLN expression in CRC with clinical features and to determinate the prognostic significance of ANLN expression in CRC. METHODS: The ANLN expression in CRC tissue and adjacent normal colorectal mucosa were measured, the relationship between ANLN expression and clinical features as well as overall survival were analyzed. RESULTS: ANLN was overexpressed in CRC. ANLN expression was associated with tumor invasion and enlarged tumor size. …Furthermore, Kaplan-Meier survival analysis revealed that higher expression of ANLN was associated with poorer overall survival. Multi-variate analysis suggested that higher expression of ANLN, preoperative CEA level and distant metastasis were independent prognostic factor in patients with CRC CONCLUSIONS: ANLN expression is elevated in CRC and has a strong potential to act as a biomarker for the prognosis of CRC. Show more

Keywords: Colorectal cancer, ANLN, prognosis

DOI: 10.3233/CBM-160585

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 459-465, 2016

Authors: Xu, Xiao-Feng | Lu, Ren-Quan | Xiao, Ran | Zhou, Lei | Zhao, Xin-Min | Hu, Xi-Chun | Gao, Xiang | Guo, Lin

Article Type: Research Article

Abstract: BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer. OBJECTIVE: This study aimed to detect the expression of Epstein-Barr viral Rta protein in patients with untreated NPC, and compare the serum Rta-IgG with the VCA-IgA in patients with NPC. METHODS: In the current work, the nasopharyngeal tissues of untreated NPC patients (n= 13) and non-NPC controls (n= 10) were collected for the immunohistochemical (IHC) staining to analyze the levels of Rta protein expression, meanwhile serum samples from the participants were prepared to assess the roles of Rta-IgG level with …Enzyme-linked immunosorbence assay (ELISA) in diagnosis of NPC including the patients with NPC, the patients with other cancers, and normal volunteers. RESULTS: The levels of serum Rta-IgG in 26 NPC patients were monitored at pre- and post-treatments, as well as one to two year after. We found that there was a significant difference of the expression levels of Rta protein between NPC and non-NPC groups (P< 0.05). Correspondingly, the levels of serum Rta-IgG in NPC patients (3.05, 1.19-4.95) were significantly higher than those of non-NPC participants (0.15, 0.08-0.30, P< 0.05) including the patients with lung cancer (0.14, 0.08-0.19), the patients with breast carcinoma (0.17, 0.10-0.25), the patients with gastric carcinoma (0.08, 0.05-0.16), the patients with malignant lymphoma (0.13, 0.08-0.20), the patients with benign nasopharyngeal disease (1.65, 0.74-1.93) and healthy volunteers (0.22, 0.13-0.32), respectively. With a receiver operation characteristic (ROC) analysis, the cut-off value to discriminate NPC patients from the controls was established at 0.92 (S/CO) for Rta-IgG (sensitivity 83.6%; specificity 82.4%), the diagnosis efficacy of Rta-IgG was higher than VCA-IgA. The positive rates of Rta-IgG were related to clinical stage, but not metastatic sites. Serum concentrations of Rta-IgG were decreased in NPC patients with effective radiation, and slightly raised or with no change with ineffective radiation. CONCLUSIONS: Rta expression levels are elevated in the patients with NPC, and serum Rta-IgG is a promising biomarker in both differential diagnosis and therapy-monitoring of the patients with NPC. Show more

Keywords: Nasopharyngeal carcinoma, Epstein-Barr virus, Rta protein, VCA-IgA, Enzyme-linked immunosorbent assay (ELISA)

DOI: 10.3233/CBM-160586

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 467-476, 2016

Authors: Li, Zhen | Shu, Jinian | Zhang, Peng | Sun, Wanqi | Yang, Bo | Zhang, Haixu

Article Type: Research Article

Abstract: BACKGROUND: Identifying endogenous volatile organic compounds (VOCs) as markers for different cancers currently requires time-consuming procedures and specialized operators. OBJECTIVE: The objective of this study was to develop a rapid and simple method for measuring VOCs at trace levels. METHODS: A simple vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS) was used to detect trace levels of dimethyl trisulfide (DMTS), dimethyl sulfide (DMS), and 2-butanone, which correspond to volatile biomarker candidates present in the exhaled breath of patients with breast, liver, and lung cancers, respectively. The practicality of measuring endogenous VOCs using VUV-PIMS was confirmed …by detecting them in cultured cell lines. RESULTS: The abovementioned VOCs were detected with high sensitivity by VUV-PIMS. The limits of detection (LODs) for DMTS, DMS, and 2-butanone were 3.1, 3.9, and 23.2 pptv, respectively, under ambient conditions, which surpass the sensitivity of nearly all other MS-based techniques. Moreover, relatively high concentrations of 2-butanone and DMS were observed in VOCs emitted from the A549 lung cancer cell line and the HepG2 liver cancer cell line, respectively. CONCLUSIONS: Our results show that VUV-PIMS may serve as a reliable method for real-time measurement of endogenous volatile cancer biomarkers. Show more

Keywords: VUV-PIMS, cancer, endogenous VOCs, cell measurement

DOI: 10.3233/CBM-160587

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 477-487, 2016

Authors: Kanmaz, Zehra Dilek | Aras, Gülfidan | Tuncay, Esin | Bahadır, Ayşe | Kocatürk, Celalettin | Yaşar, Zehra Asuk | Öz, Büge | Özkurt, Canan Ünlü | Gündoğan, Cihan | Çermik, Tevfik Fikret

Article Type: Research Article

Abstract: AIM: The aim of this study is to evaluate the diagnostic value of PET-CT scan for the prediction of EGFR mutation status and the contribution of TTF-1 expression to PET-CT scan. METHODS: We retrospectively studied 218 cases with a diagnosis of pulmonary adenocarcinoma between 2012-2014 which underwent EGFR analysis, TTF-1 and PET-CT before treatment. RESULTS: The EGFR mutation was present in 28.9% (n= 63) of cases. TTF-1 positivity was 66.9% (n= 105). Standardized uptake value (SUV max) was 16.7 ± 6.8 in EGFR mutant type, 13.8 ± 7.6 in cases having no …EGFR mutations. According to our evaluations, high SUVmax is positively correlated with EGFR mutation status. TTF-1 expression in multivariate analysis strengthens the accuracy of detecting an EGFR mutation. CONCLUSION: PET-CT FDG uptake may, together with TTF-1 expression, help diagnosis in lung adenocarcinoma cases when evaluating for EGFR mutation status. Show more

Keywords: Lung cancer, EGFR, TTF-1

DOI: 10.3233/CBM-160588

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 489-498, 2016

Authors: Kazemzadeh, Mina | Safaralizadeh, Reza | Feizi, Mohammad Ali Hosseinpour | Ravanbakhsh, Reyhaneh | Somi, Mohammad Hossein | Hashemzadeh, Shahryar

Article Type: Research Article

Abstract: Colorectal cancer (CRC) is one of the most common cancers in the world; therefore, extensive research is needed to find new molecular therapeutic targets and biomarkers. LncRNA (long non-coding RNA), a new class of non-coding RNAs, has a crucial role in the onset and progression of various cancersincluding colorectal cancer. Research on lncRNA is still at initial stages and underlying molecular mechanisms of the vast majority of lncRNA have remained unclear. LOC100287225 is one of these novel lncRNAs (long intergenic non-coding RNA) located in the long arm of the chromosome 18. The purpose of this study was to determine the …expression of LOC100287225 in colorectal tissue, and its misregulation in CRC patients. Quantitativereal-time-PCR (qRT-PCR) was used to investigate the LOC100287225 expression in pairs of tumorous and adjacent tumor-free tissues of 39 colorectal cancer patients. Also, the relationship between the clinicopathology and expression of LOC100287225 was determined. QRT-PCR results revealed that not only is LOC100287225 expressed in the intestinal tissue, but has also been misregulated during tumorigenesis. Moreover, LOC100287225 RNA relative expression levels were significantly lower in tumor tissues compared with adjacent tumor-free tissues (P< 0.001). RNA expression level of LOC100287225 did not show significant correlation with clinical characteristics. In conclusion, our study demonstrated that LOC100287225 misregulation couldbe a potential target for gene therapy in colorectal cancer. Show more

Keywords: CRC, lincRNA, LOC100287225, qRT-PCR

DOI: 10.3233/CBM-160589

Citation: Cancer Biomarkers, vol. 16, no. 3, pp. 499-505, 2016