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