Cancer Biomarkers - Volume 16, issue 4

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