Cancer Biomarkers - Volume 15, issue 4

Authors: Tian, Tian | Gu, Xiaobin | Zhang, Bo | Liu, Yang | Yuan, Chao | Shao, Lijuan | Guo, Yajun | Fan, Kexing

Article Type: Research Article

Abstract: BACKGROUND: High expression of CD14(+)HLA-DR-/low myeloid-derived suppressor cells (MDSCs) is correlated with immunosuppressive activity in various cancers, however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in small-cell lung cancer (SCLC) patients. OBJECTIVE: The purpose of the study was to investigate the number, frequency and clinical significance of CD14(+)HLA-DR-/low MDSCs in SCLC patients. METHODS: The peripheral blood of 42 patients with SCLC and 37 healthy controls was analyzed by using flow cytometry. The relationships between the number and frequency of MDSCs, clinicopathological features and overall survival(OS) were analyzed. …The prognostic value of MDSCs was tested by using univariate and multivariate analysis. RESULTS: Our results demonstrated that number and frequency of peripheral CD14(+)HLA-DR-/low MDSCs were significantly increased in SCLC patients than in controls (p< 0.0001 and p< 0.0001, respectively). The frequency of MDSCs correlated with tumor stage (p= 0.02), serum LDH levels (p= 0.001) and with the poorer OS (log-rank test, p= 0.017). Univariate and multivariate analyses suggested that frequency of CD14(+)HLA-DR-/low MDSCs as an independent biomarker for poor prognosis in SCLC patients during follow-up. Our study provides the first evidence that the frequency of CD14(+)HLA-DR-/low MDSCs negatively correlates with clinical outcomes in SCLC patients. CONCLUSIONS: The frequency of CD14(+)HLA-DR-/low MDSCs could be considered as a poor prognostic predictor in SCLC and the elimination of MDSCs during medical interventions may improve the prognosis of SCLC patients. Show more

Keywords: Small-cell lung cancer, myeloid-derived suppressor cells, prognosis, biomarker

DOI: 10.3233/CBM-150473

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 425-432, 2015

Authors: Hiura, Kazuya | Shiraishi, Akiko | Suzuki, Chinami | Takamura, Kei | Yamamoto, Makoto | Komori, Hitoshi | Watanabe, Yasuhiro | Iwaki-Egawa, Sachiko

Article Type: Research Article

Abstract: BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. OBJECTIVE: To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. METHODS: Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. RESULTS: There were no significant differences in these markers levels between groups. However, …the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC < median, n= 10), former group showed a significant improvement in the median progression-free survival compared with latter group (636 vs. 196 days, p = 0.032). CONCLUSIONS: MMP-9/ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy. Show more

Keywords: Absolute neutrophil count, matrix metalloproteinase-9, progression-free survival, tumor reduction rate, VEGF

DOI: 10.3233/CBM-150483

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 433-440, 2015

Authors: Abdel Salam, R. | El-Badry, N. | Rizk, A. | El-Sedfy, A. | Kamel, N. | El-Abd, E.

Article Type: Research Article

Abstract: BACKGROUND: Thyroid nodules require pre-surgical cytological assessment for possible risk of malignancy. Many techniques were introduced to enhance differential diagnosis and to avoid unnecessary diagnostic surgery. OBJECTIVE: The study aims to investigate the potential use of ECM1 gene and MMP-2 protein as preoperative tumor markers in suspicious follicular thyroid lesions. METHODS: The study included 40 Egyptian cases with solitary thyroid nodules. They underwent preoperative FNAB followed by thyroidectomy. MMP-2 protein and ECM1 gene were detected using immunostaining and conventional semi-quantitative RT-PCR techniques; respectively. The diagnostic accuracy of FNAB, gene and protein expression level cutoffs …was calculated by using ROC. RESULTS: Both MMP-2 protein and ECM1 gene expressions were significantly higher in malignant than benign group (P < 0.001). Both were significantly higher in higher tumor stages (PMMP-2 = 0.002; PECM1 = 0.032) but only ECM1 significantly differed with tumor size (P < 0.006). The diagnostic performances of ECM1 expression scores was significantly better than that of FNAB (P = 0.049). A significant direct correlation was detected between ECM1 gene and MMP-2 protein expressions in cases of FVPC and of FC (P = 0.014). CONCLUSIONS: MMP-2 protein and ECM1 gene are useful preoperative markers for defining malignancy in suspicious thyroid nodules. Show more

Keywords: ECM1 (Extracellular matrix protein 1), FNAB (fine needle aspiration biopsy), immunostaining, MMP-2 (Matrix metalloproteinase-2), RT-PCR (reverse transcriptase-polymerase chain reaction), thyroid nodules

DOI: 10.3233/CBM-150481

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 441-458, 2015

Authors: Khan, Mosin S. | Pandith, Arshad A. | Masoodi, Shariq R. | Khan, Shoukat H. | Rather, Tanveer A. | Andrabi, Khursid I. | Mudassar, Syed

Article Type: Research Article

Abstract: BACKGROUND: Among various polymorphic variants of TP53 gene, codon 72 polymorphism (Arg72Pro) has been found to be associated with cancer susceptibility, but only few studies have investigated their effect on thyroid cancer risk. OBJECTIVE: A case control study was conducted to elucidate the possible role of this SNP as risk factor in thyroid cancer development and to examine its correlation with various clinicopathological variables. METHODS: In this study, we tested the genotype distribution by PCR-RFLP in 140 thyroid cancer patients and 200 cancer-free controls from Kashmir Valley. RESULTS: Genotype frequencies of …Arg/Arg (GG), Arg/Pro (GC), and Pro/Pro (CC) genotypes among cases were 0.286, 0.343 and 0.371 while in controls 0.45, 0.37 and 0.18 respectively. Proline allele frequency was significantly higher than arginine frequency in patient group (OR = 2.06, 95% C.I = 1.5-2.8). Significant association was found between variant genotype of codon 72 of TP53 gene and young age group, female gender, urban dwellers, non-smokers and patients with elevated TSH levels (P < 0.05). CONCLUSION: It is evident from our study that Arg72Pro SNP of TP53 gene is connected with higher susceptibility to thyroid cancer especially in young age group, female gender, non-smokers and patients with elevated TSH levels, hence, implicated in thyroid carcinogenesis. Show more

Keywords: Papillary thyroid cancer, thyroid stimulating hormone, benign thyroid disease, differentiated thyroid cancer, polymerase chain reaction, restriction digestion

DOI: 10.3233/CBM-150485

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 459-465, 2015

Authors: Chen, Zhanwei | Wu, Haiwei | Huang, Shengyun | Li, Wengang | Zhang, Shizhou | Zheng, Peihui | Zhou, Xiaoqing | Liu, Wenlei | Zhang, Dongsheng

Article Type: Research Article

Abstract: BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3 (BNIP3) has been explored in many human malignancies, but not in adenoid cystic carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of expression of BNIP3 in ACC tissues and cells and elucidated its correlations to hypoxia-induced autophagy. METHODS: Immunohistochemical and immunofluorescence staining were used to explore BNIP3, HIF-1α and LC3 expression. RESULTS: BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P= 0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly …correlated with TNM stage (P= 0.023) and histological grade (P= 0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P= 0.019). The expression of BNIP3 was correlated with HIF-1α expression (P= 0.011). The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P= 0.011). In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and could be a new target for gene therapy of adenoid cystic carcinoma. Show more

Keywords: Adenoid cystic carcinoma, hypoxia, BNIP3, HIF-1α, autophagy

DOI: 10.3233/CBM-150474

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 467-475, 2015

Authors: Ouyang, Huoniu | Guo, Zhilin | Cheng, Zhihua | Guo, Yu

Article Type: Research Article

Abstract: BACKGROUND: Glioma is one of the most common primary malignant brain tumors. However, the potential molecular mechanism of glioma tumorigenesis is limited. In this study, we aimed to investigate the functional relationship between glioma and a potential tumor related gene JUB . METHODS: Lentivirus-based RNA interference was carried out to knock down JUB expression in human glioma cells U251. The effects of JUB on cell proliferation and cell cycle were detected by MTT, colony formation and flow cytometry assays. RESULTS: Lentivirus-mediated shRNA could effectively suppress JUB expression in …U251 cells, resulting in significant decreases in cell proliferation and colony formation. Flow cytometry analysis showed that JUB silencing blocked cell cycle at S and G2/M phases, and induced apoptosis, which could contribute to cell growth suppression. Furthermore, knockdown of JUB caused downregulation of CDK6 and activations of Caspase 3 and PARP. CONCLUSIONS: The results in this study uncovered that JUB was a regulator involved in proliferation of glioma cells, and it could be used as a potential therapeutic target for glioma. Show more

Keywords: Glioblastomas, JUB, proliferation, RNA interference, ajuba LIM protein

DOI: 10.3233/CBM-150491

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 477-484, 2015

Authors: Nuerrula, Yiliyaer | Rexiati, Mulati | Liu, Qiang | Wang, Yu-Jie

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Looking for tumor markers by using protein chip technology is one of the hot topics, but many studies are still limited on short term detection of differential expressed proteins before and after surgery among patients with RCC. This study analyzed differential expressed serum protein and its clinical significance with clear-cell renal cell carcinoma to further measurement of the rule of variable expressing. METHODS: Eighty-nine patients with clear-cell renal cell carcinoma who underwent surgery from November 2013 to 2014 and postoperatively confirmed by pathology were entered in RCC group, 100 healthy volunteers and patients …without RCC who underwent medical examination in the same period were entered in control group. The serum protein were analyzed in both group before surgery and every regular follow-up period in 1 year after surgery with RCC group. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and weak cation exchange protein chip (CM10) technology systems were used for identifying differential expressed serum protein in RCC group and controls. The linear support vector machine (SVM) was applied to establish the diagnostic model of protein fingerprints and the leave-one-out cross validation was used for determining model discriminating effect. The differential expressed proteins were analyzed by ZUCI-PDAS protein spectral data analysis system. RESULTS: Five kinds of proteins were identified as potential biomarker, ultimately. The M/Z of these proteins was 15953, 7987, 9304, 8948, 5911, respectively. There were significant difference on expression level of these proteins with two groups preoperatively (P< 0.05). Comparison of all postoperative expression levels to preoperative one and each differential level mutually between a year in postoperative period also revealed statistical significance (P< 0.05). With taking identified proteins as biomarker, the sensitivity and specificity in predicting clear-cell renal cell carcinoma was 88.8% (79/89) and 91.0% (91/100), respectively. CONCLUSION: The corresponding specific protein was Bcl-2 family apoptosis regulatory proteins, WAP four-disulfide core protein, Krueppel-like factor 8, monocyte chemotactic protein-1, serum amyloid β -protein-4, respectively, and will may serve as tumor markers of kidney cancer. These proteins manifests high predictive value for clear-cell renal cell carcinoma, and may contribute to therapeutic evaluation, prognosis and targeted therapy for clear-cell renal cell carcinoma. Show more

Keywords: Clear cell renal cell carcinoma, proteomics, tumor marker, expression

DOI: 10.3233/CBM-150490

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 485-491, 2015

Authors: Yoshimoto, Chiharu | Iwabuchi, Takuya | Shigetomi, Hiroshi | Kobayashi, Hiroshi

Article Type: Research Article

Abstract: OBJECTIVE: The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts. METHODS: Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery. RESULTS: The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 …mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels. CONCLUSIONS: We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis. Show more

Keywords: Endometriosis, malignant transformation, iron, cyst fluid

DOI: 10.3233/CBM-150484

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 493-499, 2015

Authors: Sarma, Anupam | Hazarika, Munlima | Das, Debabrata | Kumar Rai, Avdhesh | Sharma, Jagannath Dev | Bhuyan, Chidananda | Kataki, Amal Chandra

Article Type: Research Article

Abstract: BACKGROUND: Acute leukemia is a heterogenous disease having diverse phenotypes. Immunophenotyping by flowcytometry is essential for diagnosis of myeloid and lymphoid subtypes. Aberrant phenotype incidence is controversial and dissimilar results have been reported by different groups. OBJECTIVES: Purpose of the study was to determine the incidence of aberrant phenotypes in North East Indian patients with acute leukemia. METHODS: We analysed a total of 100 cases (AML = 36, ALL = 61, MPAL = 3) by multiparametric flow cytometry using an acute panel of monoclonal antibodies (MoAbs). The MoAbs were selected to identify differentiation-associated antigens …of both myeloid and lymphoid lineages. RESULTS: Aberrant phenotypes were found in 21 (58.3%) cases of AML, 36 (59.2%) cases of B-ALL and 6 (66.7%) cases of T-ALL. CD7 was the most frequent lymphoid associated antigen found in 33% of AML cases while CD117 was the myeloid antigen most frequently detected in ALL (54%) cases. Aberrant expression of CD 117 is highly significant by Fischer's exact test (P< 0.0001). CONCLUSION: We conclude that aberrant phenotypes are present in a great majority of acute leukemia patients of North East India. Future studies will be directed to correlate of these markers with prognosis and therapeutic response. Show more

Keywords: Acute leukemia, flow cytometry, aberrant phenotype, CD marker

DOI: 10.3233/CBM-150482

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 501-505, 2015

Authors: Dai, Shu-Long | Zhou, Jin | Pan, Chao | Huang, Guan | Shi, Zuo-Liang | Yang, Shi-Yong | Yang, Kun-Xing

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-145 (miR-145) plays a crucial role in cancer prognosis. OBJECTIVE: This study aimed to investigate the prognostic value of miR-145 in patients with various cancers. METHODS: We pooled published literature from PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews and calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the correlation between miR-145 expression levels and survival of patients with general cancers. RESULTS: A total of 615 cases from 8 studies of multiple cancers were examined in this meta-analysis. The HR for overall survival (OS) …of low miR-145 expression in multiple cancers was 1.80 (95% CI = 1.19-2.70). Furthermore, after excluding 1 study for its potential heterogeneity, the results suggested an increasing prognostic value of low miR-145 expression (HR = 2.20, 95% CI = 1.63-1.97). In addition, there was no significant difference between miR-145 expression levels and recurrence-free survival (RFS). CONCLUSION: In conclusion, our findings suggest that miR-145 expression is associated with OS in cancer patients and can serve as a promising biomarker for monitoring prognosis. Show more

Keywords: microRNA-145, cancer, prognosis, meta-analysis

DOI: 10.3233/CBM-150475

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 507-513, 2015

Authors: Mazurek, Agnieszka | Pierzyna, Magdalena | Giglok, Monika | Dworzecka, Urszula | Suwiński, Rafaƚ | Maƚusecka, Ewa

Article Type: Research Article

Abstract: BACKGROUND: Analysis of circulating cell-free DNA in blood is considered as a liquid biopsy, which enables non-invasive and repetitive investigation of the tumor DNA. The potential clinical usefulness of circulating DNA is frequently examined in lung cancer. Thus, our aim was assessment if chemotherapy influences the circulating DNA concentration. PATIENTS AND METHODS: Fifty-seven lung cancer patients in advanced stages of the disease were examined. Quantification of circulating DNA was determined by TERT amplification. RESULTS: Distant metastases and chemotherapy were significantly connected with circulating DNA level. Patients treated with conventional chemotherapy had statistically lower circulating …DNA levels when compared to patients not treated with chemotherapy. Histological types of tumor and smoking status were not associated with circulating DNA concentration. In this study, we have also genotyped the EGFR mutations in exon 19 of circulating DNA using the TaqMan PCR assays. One patient carried a deletion (2235-49del in EGFR), which has been confirmed by sequencing. CONCLUSIONS: Circulating DNA is easy to obtain, convenient biological material, although quantitative analysis cannot be used as diagnostic tool, but it can be applied to determination of EGFR mutations, basis of the tyrosine kinase inhibitors application. Show more

Keywords: Circulating DNA, cell-free DNA, lung cancer, liquid biopsy, chemotherapy

DOI: 10.3233/CBM-150471

Citation: Cancer Biomarkers, vol. 15, no. 4, pp. 515-524, 2015