Cancer Biomarkers - Volume 16, issue 4

Authors: Zhao, Teng | Cui, Longjiu | Li, Aijun

Article Type: Research Article

Abstract: BACKGROUND: Red blood cell distribution width (RDW) is a parameter reported in blood routine examination, and has been reported as an inflammatory biomarker. The objective of this study was to investigate the significance of RDW in patients with hepatocellular carcinoma after radical resection. METHOD: The relationship between the preoperative serum RDW value and clinic pathologic characteristics was analyzed in 106 HCC patients who underwent curative resection of hepatocellular carcinoma. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: The RDW levels were divided …into two groups: high RDW (> 14.5%) and low RDW (≤ 14.5%), (n= 28 vs n= 78). The patients with preoperative high levels of RDW had significantly worse survival than those with low RDW (p< 0.05). According to multivariate analysis, high RDW (HR = 1.89, p= 0.002), TNM stage (HR = 1.70, p= 0.019), tumor size (HR = 1.33, p= 0.045), tumor number (HR = 1.42, p= 0.027) and vascular invasion (HR = 1.64, p= 0.009) were independent prognostic factors of OS. CONCLUSIONS: Preoperative high levels of RDW are associated with poor survival. It might be an independent prognostic factor in patients with hepatocellular carcinoma. Show more

Keywords: Red blood cell distribution width, hepatocellular carcinoma, prognosis

DOI: 10.3233/CBM-160591

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 507-512, 2016

Authors: Ribeiro, Karen Bento | da Silva Zanetti, Juliana | Ribeiro-Silva, Alfredo | Rapatoni, Liane | de Oliveira, Harley Francisco | da Cunha Tirapelli, Daniela Pretti | Garcia, Sergio Britto | Feres, Omar | da Rocha, José Joaquim Ribeiro | Peria, Fernanda Maris

Article Type: Research Article

Abstract: INTRODUCTION: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation. OBJECTIVE: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome. MATERIAL AND METHODS: Fifty-eight samples of tumor tissue samples of metastatic colon …adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray. RESULTS: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007). CONCLUSION: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis. Show more

Keywords: Colon cancer, KRAS mutation, cancer stem cell, biomarker

DOI: 10.3233/CBM-160592

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 513-521, 2016

Authors: Jiang, Yuanyuan | Xu, Huan | Jiang, Hongmin | Ding, Siyi | Zheng, Taiqing

Article Type: Research Article

Abstract: BACKGROUND: Inflammation plays a pivotal role in cancer development and progression. Neutrophil-lymphocyte count ratio (NLR) is an indicator of systemic inflammatory response which is supposedly associated with gastric cancer (GC) development and progression. Since this parameter can be easily obtained from routine blood examination, it will be a great economic relief to gastric patients if we can bring it into clinical application. OBJECTIVE: The current study aims to evaluate the pretreatment NLR in gastric cancer patients through retrospectively reviewing the medical records. METHODS: A total of 327 patients hospitalized on a tertiary care …hospital were retrospectively investigated and divided into two groups. Gastric cancer group were composed of patients with newly diagnosed, pathologically confirmed GC and the control group were patients with gastric polyp or benign gastric stromal tumor. The value of NLR in the presence and stage of gastric cancer was investigated in the entire gastric cancer group. RESULTS: Our study showed levels of NLR were significantly higher in gastric cancer cohort (2.17 (1.63-3.09) versus 1.62 (0.85-2.32), p< 0.001). After all the known confounders were excluded, NLR was an independent predicator of GC (OR = 1.446, 95%CI (1.121-1.866), and P= 0.005). Area under ROC curve (AUC) of NLR was 0.694. In addition, the results of Spearman's correlation showed NLR may have a positive correlation with size of tumor, N-stage, distant metastasis, and overall stage (r = 0.256, 0.256, 0.161 and 0.171, resp., all p < 0.05). CONCLUSIONS: The current study demonstrated that pre-treatment NLR may be a useful biomarker in the health care of gastric cancer patients. Show more

Keywords: Gastric cancer, neutrophil lymphocyte ratio, routine blood examination, inflammation biomarker, retrospective study

DOI: 10.3233/CBM-160593

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 523-528, 2016

Authors: Wang, Yu | Jiang, Xiaorong | Dong, Shaoliang | Shen, Jiankun | Yu, Haixia | Zhou, Ji | Li, Jin | Ma, Hongbo | He, Ellen | Skog, Sven

Article Type: Research Article

Abstract: BACKGROUND: The World Health Organization (WHO) has estimated that the number of cancer patients will increase by about 70% during the next 25 years world-wide. To deal with this problem, WHO has suggested a focus on prevention of tumor incidence and health screening for early detection of people with tumors. OBJECTIVE: To investigate the use of thymidine kinase 1 (TK1), CEA and AFP in serum to discover people with malignant tumors through health cancer screening. METHODS: Of a cohort in 486,085 people of a routine health screening at the Health Centre, Fujun 180 …Hospital, Quanzhou city, China, 56,286 people were investigated according to the presence of cancer during 2009-2014. The concentration of CEA and AFP were determined by an electrochemiluminescence immunoassay from Roche Diagnostics e601GmbH and STK1 by a commercial kit based on an enhanced chemiluminescent dot blot assay. RESULTS: The cancer incident rate increased from 0.048/100,000 to 0.220/100,000. The most common types of tumors were those of the liver, cervix and lung. STK1 correlated to tumor growth rate, was more sensitive than CEA and AFP for discovering people with malignant tumors and more sensitive among people who had diagnosis of malignant tumor. STK1 was also a prognostic biomarker for death at 10-40 months follow-up, while CEA and AFP were not. A combination of these markers increased the sensitivity by about 30%. CONCLUSION: STK1 is a reliable biomarker for discovering people with malignant tumors in cancer screening. Show more

Keywords: Thymidine kinase 1 (TK1), CEA, AFP, health screening

DOI: 10.3233/CBM-160594

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 529-536, 2016

Authors: Hogendorf, Piotr | Durczyński, Adam | Skulimowski, Aleksander | Kumor, Anna | Poznańska, Grażyna | Strzelczyk, Janusz

Article Type: Research Article

Abstract: BACKGROUND: Currently pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Because of its late manifestation and consequent dismal prognosis, there is an urgent need to develop highly sensitive and specific marker. Neutrophil Gelatinase-Associated Lipocalin (NGAL) recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE: Our aim was to assess the potential of urine and bile concentration of NGAL in differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Forty-two patients operated on due to pancreatobiliary lesions were enrolled in this study. All enrolled patients had eGFR …within reference range. Levels of CEA, CA 125 and Ca19-9 were assessed using standard laboratory protocols. A sample of urine was collected prior to the surgery. Intraoperatively a 5 ml sample of bile was collected directly from the common bile duct. Bile and urine levels of NGAL were measured using a ELISA kit. After standard pathological examination of specimens obtained during surgery, patients were divided into 2 groups: 21 patients with pancreatic adenocarcinoma and 15 patients with focal chronic pancreatitis. RESULTS: NGAL concentration in bile in patients with PDAC vs CP was 75.72 ± 16.05 ng/mL vs 62.62 ± 18.6 ng/mL respectively (p= 0,011). NGAL concentration in urine was 43.26 ± 21.21 ng/mL vs 17.96 ± 14.58 ng/mL (p= 0.002) respectively. In order to compare these markers with routinely used ones, ROC curve was built for Ca125 to establish cutoff point and in case of CA19-9 clinically used cutoff (≥ 37U/mL) was applied. Sensitivity and specificity for NGALurine with cutoff value of 27 ng/mL was 80.95% and 80% respectively, while these values for NGALbile were 71.43% and 80% respectively. Ca19-9 measured in plasma with clinically used cutoff value had sensitivity of 71.43% and specificity of 73.33%. Sensitivity and specificity for Ca 125 measured in plasma with cutoff value of 13 U/mL were 85.71% and 66.67% respectively. CONCLUSIONS: In conclusion, NGAL in urine and bile are remarkably accurate in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Therefore, NGAL concentrations in bile and urine should be further investigated in order to assess their usefulness in early pancreatic adenocarcinoma diagnosis. Show more

Keywords: Pancreatic cancer, pancreatic adenocarcinoma, focal chronic pancreatitis, cancer biomarker, Neutrophil Gelatinase Associated Lipocalin

DOI: 10.3233/CBM-160595

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 537-543, 2016

Authors: Jafarzadeh, A. | Fooladseresht, H. | Nemati, M. | Assadollahi, Z. | Sheikhi, A. | Ghaderi, A.

Article Type: Research Article

Abstract: BACKGROUND: The CXCL10 receptor, CXCR3, is preferentially expressed on Th1 and NK cells. Therefore, CXCL10 acts as a chemoattractant for these cells. OBJECTIVE: The aim was to evaluate the CXCL10 levels and a single nucleotide polymorphism (SNP), rs4508917, in chemokine gene, in patients with breast cancer (BC). METHODS: A total of 200 subjects including 100 women with BC and 100 healthy women were enrolled into study. The serum CXCL10 levels were measured by ELISA and the SNP rs4508917 was determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). RESULTS: The CXCL10 …levels were significantly higher in patients than control group (P< 0.0001). There was also significant difference between tumor stages regarding the CXCL10 levels (P< 0.0001). The frequencies of GG genotype and G allele at rs4508917 were significantly higher in patients than controls (P< 0.0001). The CXCL10 levels were higher in patients with GG genotype whereas they were lower in healthy subjects having GG genotype as compared with those having AA genotype at rs4508917 (P< 0.001). CONCLUSION: Higher CXCL10 levels in patients with BC represent that the chemokine may contributes in tumor development. The rs4508917 may play a role in the susceptibility to BC. Different association was also observed between rs4508917 and CXCL10 levels in patients with BC and healthy subjects. Show more

Keywords: Breast cancer, chemokine, CXCL10, gene polymorphism, rs4508917

DOI: 10.3233/CBM-160596

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 545-554, 2016

Authors: González, Miriam García | Vela, Diego | Álvarez, Mónica | Caramés, Jesús

Article Type: Research Article

Abstract: BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor, which can develop in nearly all anatomical locations. It is extremely rare in the duodenum and only seven cases have been reported previously. These lesions are of unknown etiology characterized by proliferation of myofibroblastic with an inflammatory infiltrate. It is considered a tumor of borderline malignancy. OBJECTIVE: We report the first case described of IMT located isolated in the third duodenal portion, which develops as a massive intestinal bleeding in a 14 years old girl. RESULTS: Complete surgical excision was successful and after …36 months of follow up the patient is asymptomatic. Show more

Keywords: Inflammatory, duodenal, massive bleeding, myofibroblastic

DOI: 10.3233/CBM-160597

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 555-557, 2016

Authors: Cybula, Magdalena | Wieteska, Ƚukasz | Józefowicz-Korczyńska, Magdalena | Karbownik, Michaƚ Seweryn | Grzelczyk, Weronika Lucas | Szemraj, Janusz

Article Type: Research Article

Abstract: BACKGROUND: Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers - and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS: We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p …and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1 , miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa. Show more

Keywords: Laryngeal squamous cell carcinoma, miRNA, expression

DOI: 10.3233/CBM-160598

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 559-568, 2016

Authors: Zhao, Ruihua | Jiang, Wenjing | Li, Xiangke | Zhang, Weijie | Song, Lijie | Chang, Zhiwei | Cao, Wei | Cao, Xinguang | Zong, Hong

Article Type: Research Article

Abstract: BACKGROUND: This study was aimed to investigating the frequency of Anaplastic lymphoma kinase (ALK) alterations in patients with gastric signet ring cell carcinoma (SRC) and the correlations between ALK alterations and the clinical-pathological features. METHODS: The expression of ALK protein was first determined in paraffin-embedded tissue specimens (FFPE) from 177 pathologically confirmed SRC patients by Ventana Immunohistochemistry (IHC). Then patients with ALK positive detected by IHC were assayed in ALK rearrangement by Fluorescence in Situ Hybridization (FISH). RESULTS: We assessed 4 of 177 cases (2.3%) as positive by IHC. 3 of the 4 …patients had T4 tumors and positive nodal status, and 1 of them had metastasis. All of them were HER2 negative. All of the 4 patients were positive for ALK rearrangement using the standard criteria of FISH. COUCLUSION: Our analysis showed that about 2.3% of Chineses SRC patients treated in our hospital were ALK positive. Ventana IHC and FISH were both of the reliable approaches in SRC patients. Patients with ALK positive seemed to have deep infiltrated and positive lymph nodes and HER2 negative. Show more

Keywords: Anaplastic lymphoma kinase (ALK), signet ring cell carcinoma (SRC), gastric cancer

DOI: 10.3233/CBM-160599

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 569-574, 2016

Authors: Mahas, Ahmed | Potluri, Keerti | Kent, Michael N. | Naik, Sameep | Markey, Michael

Article Type: Research Article

Abstract: BACKGROUND: Skin melanocytes can give rise to benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. OBJECTIVE: This substantial difference between melanoma and benign nevi can be exploited to discriminate between melanoma and benign nevi. METHODS: Array-comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA …copy number. In this study, high resolution, genome-wide single-nucleotide polymorphism (SNP) arrays were utilized to perform comprehensive and detailed analyses of recurrent copy number aberrations in 41 melanoma samples in comparison with 21 benign nevi. RESULTS: We found statistically significant copy number gains and losses within melanoma samples. Some of the identified aberrations are previously implicated in melanoma. Moreover, novel regions of copy number alterations were identified, revealing new candidate genes potentially involved in melanoma pathogenesis. CONCLUSIONS: Taken together, these findings can help improve melanoma diagnosis and introduce novel melanoma therapeutic targets. Show more

Keywords: Array comparative genomic hybridization, melanoma, FFPE

DOI: 10.3233/CBM-160600

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 575-597, 2016

Authors: Pang, Li | Wang, Da-Wei | Zhang, Nan | Xu, Da-Hai | Meng, Xiang-Wei

Article Type: Research Article

Abstract: BACKGROUND: Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. OBJECTIVE: The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. METHODS: Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival …(OS) and disease-free survival (DFS). RESULTS: Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. CONCLUSION: Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients. Show more

Keywords: Matrix metalloproteinase 11, colon cancer, prognosis, biomarker

DOI: 10.3233/CBM-160601

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 599-607, 2016

Authors: Fahrmann, Johannes F. | Grapov, Dmitry | DeFelice, Brian C. | Taylor, Sandra | Kim, Kyoungmi | Kelly, Karen | Wikoff, William R. | Pass, Harvey | Rom, William N. | Fiehn, Oliver | Miyamoto, Suzanne

Article Type: Research Article

Abstract: BACKGROUND: Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. OBJECTIVE: Identify blood-based metabolite biomarkers for diagnosing lung cancer. MEHTODS: Serum samples from subjects participating in a CT screening trial were analyzed using untargeted GC-TOFMS and HILIC-qTOFMS-based metabolomics. Samples were acquired prior to diagnosis (pre-diagnostic, n= 17), at-diagnosis (n= 25) and post-diagnosis (n= 19) of lung cancer and from subjects …with benign nodules (n= 29). RESULTS: Univariate analysis identified 40, 102 and 30 features which were significantly different between subjects with malignant (pre-, at- and post-diagnosis) solitary pulmonary nodules (SPNs) and benign SPNs, respectively. Ten metabolites were consistently different between subjects presenting malignant (pre- and at-diagnosis) or benign SPNs. Three of these 10 metabolites were phosphatidylethanolamines (PE) suggesting alterations in lipid metabolism. Accuracies of 77%, 83% and 78% in the pre-diagnosis group and 69%, 71% and 67% in the at-diagnosis group were determined for PE(34:2), PE(36:2) and PE(38:4), respectively. CONCLUSIONS: This study demonstrates evidence of early metabolic alterations that can possibly distinguish malignant from benign SPNs. Further studies in larger pools of samples are warranted. Show more

Keywords: Lung cancer, metabolomics, phospholipids, biomarkers, solitary pulmonary nodules

DOI: 10.3233/CBM-160602

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 609-617, 2016

Authors: Radwan, Sara M. | Hamdy, Nadia M. | Hegab, Hany M. | El-Mesallamy, Hala O.

Article Type: Research Article

Abstract: BACKGROUND: Beclin-1, an important autophagic gene, and hypoxia-inducible factor-1α (HIF-1α), the master regulator of the hypoxic response, are reported in several human cancers. However, their expressions in acute leukemia haven't yet been well investigated. OBJECTIVE: This study was designed to investigate the gene expression of beclin-1, microtubule-associated protein-1 light chain-3B (MAB1LC3B), the anti-apoptotic marker Bcl-2, and HIF-1α, as well as to evaluate the relationship between their expressions profile and prognosis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) adult patients. METHODS: The study involved 30 AML patients, 25 ALL patients, …and 20 controls. Gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS: In both AML and ALL groups, beclin-1 and MAB1LC3B expressions were significantly down-regulated (p < 0.001), while HIF-1α (p < 0.01) and Bcl-2 (p < 0.001) expressions were significantly up-regulated compared to the control group. HIF-1α fold expression was significantly negatively correlated with beclin-1 (p < 0.01). Moreover, decreased beclin-1 gene expression and increased HIF-1α gene expression were both associated with poor survival, supporting their pivotal role in the development and progression of acute leukemia. CONCLUSIONS: Both Beclin-1 and HIF-1α could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia. Show more

Keywords: Acute leukemia, autophagy, Beclin-1, MAP1LC3B, HIF-1α

DOI: 10.3233/CBM-160603

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 619-626, 2016

Authors: Jahed, Marzieh | Ebadi, Nader | Mivehchi, Mohamad | Majidizadeh, Tayebeh | Shahshanipour, Majid | Asgari, Mojgan | Ghadakzadeh, Sara | Hosseini, Seyed Ali

Article Type: Research Article

Abstract: BACKGROUND: Urinary bladder carcinoma is one of the leading causes of death among men, and its high recurrence rates make it one of the most solid tumors to treat. The silencing of the tumor suppressor gene by hypermethylation of the CpG islands and overexpression of proto-oncogene proteins are the main mechanisms in cancers. Here, we investigate methylation status of O6-methylguanine-DNA-methyltransferase (MGMT), a tumor suppressor gene and expression level of BCL-2 a proto-oncogene protein that is frequently observed in bladder carcinoma and its recurrences. MATERIALS AND METHODS: We analyzed the methylation of MGMT in 80 tissue …samples of patients suffering from bladder cancer and 80 urine samples of cancer-free individuals by MS-PCR. Additionally, BCL-2 protein expression level was analyzed on these 80 tissue samples by immunohistochemistry. RESULTS: 45% of patients had MGMT methylation, of which this hypermethylation does not have significant association with an increase in grade, but there was significant association in cases with recurrence tumors and metastasis tumors. Among patients with recurrence tumor, 92.5% patients showed MGMT hypermethylation; 66% of these showed BCL-2 overexpression. CONCLUSION: Our data indicate that MGMT hypermethylation and BCL-2 overexpression may have an intense role in superficial bladder cancer recurrences. Show more

Keywords: Bladder cancer, methylation, tumor suppressor gene, MGMT, BCL-2

DOI: 10.3233/CBM-160604

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 627-632, 2016

Authors: Li, Zihua | Lv, Tu | Liu, Youyu | Huang, Xuesong | Qiu, Zhongpeng | Li, Jianjun

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the expression of PARP1 in chordoma and analyzed its association with clinical factors and patients' prognosis. METHODS: The expression of Poly (ADP-ribose) polymerase 1 (PARP1) in chordoma specimens from 74 chordoma patients (50 primary and 24 recurrent tumors of 50 patients)and 20 distant normal tissue specimens was measured by immunohistochemical staining. The association of PARP1with the clinical factors and patients' prognosis was also analyzed. RESULTS: Of all the chordoma samples, 78% showed high expression of PARP1, whereas, only 10% of distant normal tissues expressed a high level of PARP1 (p< …0.01). Chi-square analysis revealed that high expression of PARP1 was significantly correlated with tumor recurrence (p< 0.01) and invasion into surrounding muscle (p< 0.01), while the data did not indicate any association with patients' gender, age, tumor location and size (p> 0.05). Kaplan-Meier survival curve and log-rank test showed that continuous disease free survival time (CDFS) was significantly shorter in the PARP1-positive group than in the PARP1-negative group (P= 0.019). CONCLUSION: High expression of PARP1 is significantly associated with chordoma invasion and recurrence. PARP1 may become a potential biomarker for chordoma in predicting its recurrence and patients' prognosis. Show more

Keywords: Chordoma, recurrence, PARP1, prognosis

DOI: 10.3233/CBM-160605

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 633-639, 2016

Authors: Li, Yu-Fen | Yang, Pei-Zhen | Li, Hua-Feng

Article Type: Research Article

Abstract: Emerging evidence showed that functional polymorphisms in the IL-10 gene may have effects on individuals' susceptibility to nasopharyngeal, oral and esophageal cancers, yet individually published findings are inconsistent. We therefore designed the meta-analysis to investigate the correlations of IL-10 genetic polymorphisms with susceptibility to nasopharyngeal, oral and esophageal cancers. The EMBASE, MEDLINE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) databases were searched with no language restrictions. We use Comprehensive Meta-analysis 2.0 software to carry out statistical analysis. Ten case-control studies with a number of 1,883 patients and 2,857 healthy subjects were enrolled. Our results revealed …that IL-10 rs1800872 T>G and rs1800896 A>G polymorphisms has a significantly association with the increased risk of esophageal cancer under the allele and dominant models; rs1800871 T>G, rs1800872 T>G and rs1800896 A>G under allele and dominant models could increase the risk of nasopharyngeal cancer; rs1800871T>G, rs1800872T>G and rs1800896 A>G SNPs under allele model were closely related to the susceptibility to oral cancer. Our findings support the point that IL-10 genetic polymorphisms may play essential role in identifying esophageal cancer, nasopharyngeal cancer and oral cancer at early stage. Show more

Keywords: IL-10, functional polymorphism, nasopharyngeal cancer, esophageal cancer, oral cancer, allele model, dominant model, subgroup analysis

DOI: 10.3233/CBM-160606

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 641-651, 2016

Authors: Chen, Wenxue | Lu, Shaohua | Ou, Jiaxian | Wang, Guifang | Zu, Yukun | Chen, Fener | Bai, Chunxue

Article Type: Research Article

Abstract: BACKGROUND: The combination of NMR spectroscopy and multivariate data analysis (MVDA), such as orthogonal partial least squares-discriminant analysis (OPLS-DA), has been collectively acknowledged as an excellent tool to investigate tissue metabolism and provide metabolite information for the diagnosis of disease, and become an important metabonomic platform for studies in biological tissues so far. METHODS: Both ex vivo high resolution magic-angle spinning1 H NMR and in vitro 1 H NMR spectroscopy technique were synchronously employed to analyze the metabonomic characteristics of 102 lung tissues from 34 patients with lung cancer in hope to identify potential diagnostic …biomarkers for malignancy detection in lung tissues. RESULTS: Significant elevations in the levels of lipids and lactate and significant reductions in the levels of myo -inositol and valine in the cancer tissues had been identified when compared with the adjacent non-involved tissues. Furthermore, the OPLSDA models calculated by two1 H NMR spectra provided for relatively high sensitivity, specificity and good prediction accuracy in the identification of class membership regardless of the number of metabolites involved. CONCLUSIONS: MVDA in combination with1 H NMR spectra highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for future lung cancer biomarker research or identification. Show more

Keywords: Lung cancer, NMR spectroscopy, metabonomics, multivariate data analysis (MVDA), diagnosis

DOI: 10.3233/CBM-160607

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 653-664, 2016

Article Type: Other

Citation: Cancer Biomarkers, vol. 16, no. 4, pp. 665-672, 2016