Cancer Biomarkers - Volume 17, issue 4

Authors: Wang, Juan | Zhang, Shufang | Ni, Weihua | Zhai, Xiaoyu | Xie, Fei | Yuan, Hongyan | Gao, Sujun | Tai, Guixiang

Article Type: Research Article

Abstract: BACKGROUND: Mucin 1 (MUC1), as an oncogene, plays an important role in the diagnosis of lung cancer. OBJECTIVE: To establish a double-antibody sandwich enzyme-linked immune sorbent assay (ELISA) kit for the detection of serum MUC1 in lung cancer patients. METHODS: Commercial mouse anti-human MUC1 monoclonal antibody and rabbit anti-human MUC1 polyclonal antibody were used to construct a double-antibody sandwich ELISA kit. The serum MUC1 levels in peripheral blood of lung disease patients and healthy individuals were detected by the double-antibody sandwich ELISA kit and CA15-3 kit, respectively. RESULTS: A double-antibody …sandwich ELISA kit was successfully constructed, and the sensitivity was up to 0.5 μ g/l. The cut-off value for the serum MUC1 levels in the peripheral blood was 1.98 μ g/l, the sensitivity was 62.5%, the specificity was 100% and the Youden index was 0.6250 when detected by the double-antibody sandwich ELISA kit, while the sensitivity was 18.75%, the specificity was 100% and the Youden index was 0.1875 when detected by CA15-3 kit. CONCLUSION: The double-antibody sandwich ELISA kit is superior to the CA15-3 kit in the detection of serum MUC1 in lung cancer patients, suggesting an attractive applying of the double-antibody sandwich ELISA kit in the early diagnosis of lung cancer. Show more

Keywords: MUC1, anti-MUC1 polyclonal antibody, ELISA, CA15-3, lung cancer

DOI: 10.3233/CBM-160649

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 369-376, 2016

Authors: Li, Shu-Xia | Yang, Yan-Qi | Jin, Li-Jian | Cai, Zhi-Gang | Sun, Zheng

Article Type: Research Article

Abstract: INTRODUCTION: The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. MATERIALS AND METHODS: The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. …RESULTS: The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P < 0.05), but there was no significant difference in the content of the above factors in the serum sample between two groups. There was no significant difference in the ErbB2 content in the saliva, serum or local tumor-exfoliated cells between two groups. CONCLUSION: Survivin and CEA levels are significantly increased in the saliva and local tumor-exfoliated cells in OSCC patients, and they can be used as reliable markers for the early detection of oral malignant cancer. Show more

Keywords: Oral squamous cell carcinoma, detection, survivin, CEA, ErbB2

DOI: 10.3233/CBM-160651

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 377-382, 2016

Authors: Yang, Hai-Su

Article Type: Research Article

Abstract: BACKGROUND: Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation. OBJECTIVE: The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets. METHODS: The specimens were tested with immunohistochemistry, flow cytometry, RT-PCR and fragment analysis. RESULTS: In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present …in this patient. CONCLUSION: These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not mutually exclusive and the actual frequency of simultaneous JAK2 V617F and CALR mutations is unknown. Whether the coexistence of these mutations imposes any biological or clinical significance awaits further investigation. Show more

Keywords: Lymphoproliferative neoplasm, MPNs, JAK2, CALR

DOI: 10.3233/CBM-160652

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 383-389, 2016

Authors: Maden, Muhammet | Pamuk, Omer Nuri | Pamuk, Gulsum Emel

Article Type: Research Article

Abstract: BACKGROUND: Apelin/APJ system regulates angiogenesis and is overexpressed in some malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis. OBJECTIVE: We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL); and analyzed the association between apelin levels and clinical findings. METHODS: We included consecutive 29 MM, 31 NHL patients, and 19 healthy controls. Patients' demographic and clinical features, treatment modalities, and responses were recorded from hospital records. Plasma apelin was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: MM patients had significantly higher plasma apelin level than NHL …and healthy control groups (p< 0.001). Apelin level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed that the area under the curve value for apelin level in MM was 0.842 ng/ml (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level ≥ 0.827 ng/ml had 76% sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox regression analysis showed that MM patients with high apelin level had better prognosis and patients with advanced stage of disease (ISS-3) had significantly poor prognosis when compared to others. In the MM group, apelin level correlated negatively with LDH (r = -0.39, p= 0.038). CONCLUSIONS: In MM, plasma apelin level was significantly higher than in NHL and control groups. Apelin could be playing a role in MM pathogenesis; and apelin level could be used as a diagnostic and prognostic biomarker in MM. Show more

Keywords: Multiple myeloma, non-Hodgkin lymphoma, apelin, survival

DOI: 10.3233/CBM-160654

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 391-396, 2016

Authors: Yao, Hongliang | Yang, Zhulin | Liu, Ziru | Miao, Xiongying | Yang, Leping | Li, Daiqiang | Zou, Qiong | Yuan, Yuan

Article Type: Research Article

Abstract: OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with metastasis in most patients at diagnosis. The molecular mechanisms associated with its high malignancy have not been fully elucidated. This study investigated the clinicopathological significances of GPC3 and KRT19 expression in PDAC. METHODS: GPC3, KRT19, and CA19-9 protein expression were measured by immunohistochemistry. RESULTS: GPC3 and KRT19 protein levels were overexpressed in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P< 0.01). The percentage of positive GPC3 and KRT19 expression were significantly higher in PDAC …patients with larger tumor size, poorly differentiated tumor, lymph node metastasis, invasion, and TNM stage III/IV disease than in patients with small tumor size, well-differentiated tumor, no lymph node metastasis and invasion, as well as TNM stage I/II stage disease (P< 0.05 or P< 0.01). Benign pancreatic lesions with positive GPC3 and KRT19 protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier survival analysis showed that PDAC patients with positive GPC3 and KRT19 expression survived significantly shorter than patients with negative GPC3 and KRT19 expression (P < 0.05 or P< 0.001). Cox multivariate analysis revealed that positive GPC3 and KRT19 expression were independent poor prognosis factors in PDAC patients. CONCLUSIONS: GPC3 and KRT19 overexpression are associated with carcinogenesis, progression, and poor prognosis in patients with PDAC and a valuable biomarker for diagnosis of PDAC. Show more

Keywords: Pancreatic ductal adenocarcinoma, dysplasia, pancreatic intraepithelial neoplasia, GPC3, KRT19, CA19-9, immunohistochemistry

DOI: 10.3233/CBM-160655

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 397-404, 2016

Authors: Ittel, Antoine | Zattara, Hélène | Chaix, Charlène | Michel, Gérard | Levy, Nicolas

Article Type: Research Article

Abstract: BACKGROUND: According to the World Health Organization (WHO), recurrent cytogenetic abnormalities define many specific groups of hematopoietic tumors of acute myeloid and lymphoblastic leukemia, and these abnormalities are often strongly associated with prognosis and sometimes require specific treatments. These rearrangements are commonly detected by conventional and molecular cytogenetic techniques. OBJECTIVE: Using an alternative method, we sought to highlight the presence of chromosomal rearrangements. METHODS: We applied molecular combing to detect and directly visualize gene fusions associated with balanced translocations found in acute leukemia. RESULTS: In patients harboring t(12;21)(p13;q22), we demonstrated …the presence of the fusion using specific probes covering the ETV6 and RUNX1 genes, with a positive result occurring due to the hybridization of the two probes to the same DNA fiber. Thanks to molecular combing, we also showed the presence of different breakpoints using these same probes. CONCLUSIONS: Using several probes that are specific to the most common genes involved in acute leukemia, molecular combing could be an interesting additional tool in acute leukemia diagnosis. Show more

Keywords: Molecular combing, leukemia, recurrent chromosomal abnormalities, translocation t(12;21)(p13;q22)

DOI: 10.3233/CBM-160656

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 405-409, 2016

Authors: Wƚodarczyk, Marcin | Kasprzyk, Jakub | Sobolewska-Wƚodarczyk, Aleksandra | Wƚodarczyk, Jakub | Tchórzewski, Marcin | Dziki, Adam | Dziki, Ƚukasz

Article Type: Research Article

Abstract: BACKGROUND: Rectal cancer is a major cause of death and an early diagnosis is crucial in decreasing mortality. Previous studies found a relation between chronic inflammation and increased risk of rectal cancer. It was shown that mean platelet volume (MPV) level might be a marker of subclinical inflammatory process in gastrointestinal tract. OBJECTIVE: To determinate whether MPV could be a useful biomarker of tumor progression in the rectal cancer. METHODS: One hundred and three patients with rectal cancer who underwent surgical resection of tumor were enrolled in the study. The control group consisted …of 98 healthy subjects. RESULTS: The association between MPV, tumor stage and clinical status were assessed. The analysis proved that pre-operative MPV level was significantly lower in rectal cancer vs. healthy individuals (10.65 ± 0.79 vs. 11.41 ± 0.76 fL; p < 0.001). Receiver-operating characteristic curve analysis suggested 11.3 as the cut-off value for MPV (sensitivity = 83%; specificity = 54%; AUC = 0.745). Surgical resection of tumor resulted in the increase of the MPV level with statistical significance (10.65 ± 0.79 fL vs. 11.21 ± 0.82 fL; p < 0.001). No relationship was found between the post-operative MPV level in cancer patients and control subjects. CONLUSION: MPV level may be potentially useful and easily available biomarker for monitoring subclinical inflammation related to rectal cancer and predicting tumor progression. Show more

Keywords: Biomarker, mean platelet volume, rectal cancer, tumor progression, inflammation

DOI: 10.3233/CBM-160657

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 411-417, 2016

Authors: Paik, E Sun | Shim, Minhee | Choi, Hyun Jin | Lee, Yoo-Young | Kim, Tae-Joong | Choi, Chel Hun | Lee, Jeong-Won | Kim, Byoung-Gie | Bae, Duk-Soo

Article Type: Research Article

Abstract: BACKGROUND: Epithelial ovarian cancer (EOC) is leading cause of death in gynecologic cancer, and finding prognostic factors is important for establishing treatment plans. OBJECTIVE: The aim of this study was to investigate the prognostic value of the multiplication of neutrophil and monocyte counts (MNM) in epithelial ovarian cancer (EOC). METHODS: Data were retrospectively collected from Samsung Medical Center for EOC patients treated from January 2002 to December 2012. MNM was determined by multiplying neutrophil and monocyte counts and dividing by 10,000. Sensitivity and specificity of markers were assessed using receiver operating characteristic curves. …RESULTS: We included 674 patients with EOC. For predicting overall survival (OS), the area under the curve for MNM was 0.607 (95% CI, 0.554-0.661) with sensitivity 55.2% and specificity 63.2% (cut-off value 197.40). The ability of MNM to determine OS was similar to that of the previously validated NLR and PLR. When the cohort was divided by cut-off values, poorer survival outcomes were observed in the group with higher MNM. Higher MNM was associated with advanced stage and presence of residual disease after primary treatment. CONCLUSIONS: Elevated pretreatment MNM is an independent predictor of poor survival and can be a useful biomarker in patients with EOC. Show more

Keywords: Monocytes, neutrophils, ovarian neoplasm, biological markers, prognosis

DOI: 10.3233/CBM-160658

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 419-425, 2016

Authors: Clancy, Cillian | Khan, Sonja | Glynn, Claire L. | Holian, Emma | Dockery, Peter | Lalor, Pierce | Brown, James A.L. | Joyce, Myles R. | Kerin, Michael J. | Dwyer, Roisin M.

Article Type: Research Article

Abstract: BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown. OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs. METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells …were transferred to recipient cells and the impact examined. RESULTS: Microvesicles 40-100 nm in size secreted by cell lines were visualised and confirmed to express exosomal protein CD63. HT-29 exosomes contained 409 miRNAs, HCT-116 exosomes contained 393, and 338 were common to exosomes from both cell lines. Selected targets were validated. HCT-116-379 cells showed decreased proliferation (12-15% decrease, p < 0.001) and decreased migration (32-86% decrease, p < 0.001) compared to controls. HCT-116-379 exosomes were enriched for miR-379. Confocal microscopy visualised transfer of HCT-116-379 exosomes to recipient cells. CONCLUSIONS: Colorectal cancer cells secrete a large number of miRNAs within exosomes. miR-379 decreases cell proliferation and migration, and miR-379 enriched exosomes can be engineered. Show more

Keywords: Exosomes, microRNAs, colorectal cancer

DOI: 10.3233/CBM-160659

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 427-435, 2016

Authors: Yang, Zhulin | Li, Daiqiang | Liu, Ziru | Miao, Xiongying | Yang, Leping | Zou, Qiong | Yuan, Yuan

Article Type: Research Article

Abstract: This study investigated the KLF4 and BIRC7 protein expression in malignant and benign pancreatic tissues by immunohistochemical staining and the clinical and pathological significance of KLF4 and BIRC7 expression in PDAC. KLF4 expression was significantly lower, whereas BIRC7 expression was significantly higher in PDAC than that in peritumoral tissue, benign pancreatic lesions, and normal pancreatic tissue (P < 0.01). The percentage of positive BIRC7 and negative KLF4 expression was significantly lower in PDAC patients with well differentiated tumors, maximum tumor size < 3 cm, no lymph node metastasis, no invasion to the surrounding tissues and organs, and TNM stage I/II …stage disease than in patients with poorly differentiated tumor, maximum tumor size > 5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and TNM stage III/IV disease (P < 0.05 or P < 0.01). Kaplan-Meier survival analysis showed that the differentiation, maximum tumor size, TNM stage, lymph node metastasis, invasion, negative KLF4 expression, and positive BIRC7 expression were significantly associated with the short survival of patients with PDAC (P < 0.05 or P < 0.01). Cox multivariate analysis revealed that positive BIRC7 expression and negative KLF4 expression were independent poor prognosis factors in PDAC patients. In conclusions, positive BIRC7 expression and negative KLF4 expression are associated with the progression of PDAC and poor prognosis in patients with PDAC. Show more

Keywords: Pancreatic ductal adenocarcinoma, chronic pancreatitis, pancreatic intraepithelial neoplasia, KLF4, BIRC7, immunohistochemistry

DOI: 10.3233/CBM-160660

Citation: Cancer Biomarkers, vol. 17, no. 4, pp. 437-444, 2016