Cancer Biomarkers - Volume 14, issue 4

Authors: Zhao, Wei | Zhang, Bingyuan | Guo, Xiao | Zhang, Xianxiang | Hu, Jilin | Hu, Xiao | Lu, Yun

Article Type: Research Article

Abstract: Backgroud: Hilar cholangiocarcinoma (HCC) is defined as a cholangiocarcinoma located in the bifurcation of the right and left bile duct, constituting 40%–60% of all reported cholangiocarcinoma and 58%–75% of the extrahepatic cholangiocarcinoma. In this study, we aim to investigate the expression of Ki-67, Bax and p73 in the patients with HCC, and identify their potential roles in the prognosis of HCC. Objective: Thirty five HCC patients (male: 25, female: 10) with an average age of 62.8 years were diagnosed with HCC according to the pathological tests. A total of 20 cadavers with normal hilar bile ducts were used …as control. Methods: The expression of Ki-67, Bax, and p73 was determined using immunohistochemical analysis. Results: The pathological test indicated that Ki-67 expression increased with the stage of the disease, and the infiltration of the cancer cells. Statistical difference was noted in the expression of Bax LI between the patients with HCC and normal control (32.4 ± 17.6 vs 11.2 ± 7.9, P< 0.01). Statistical difference was observed between the patients with or without lymphatic metastasis, and those of various differentiation stages (P < 0.05). Among the 35 patients with HCC, expression of p73 was observed in 11 patients (31.43%). Compared with normal control, remarkable increase of p73 expression was noted in the HCC patients (P < 0.01). Additionally, no statistical difference was noted in the expression of p73 in the patients with various disease stages, and those with or without metastasis (P> 0.05). Conclusions: Ki-67, Bax, and p73 could be used as biomarkers for the prognosis of HCC. Show more

Keywords: Hilar cholangiocarcinoma, Ki-67, Bax, p73, prognosis

DOI: 10.3233/CBM-140393

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 197-202, 2014

Authors: Yamamoto, Shinya | Chishima, Takashi | Adachi, Shouko | Harada, Fumi | Toda, Youko | Arioka, Hitoshi | Hasegawa, Naoki | Kakuta, Yukio

Article Type: Research Article

Abstract: Background: The significance of the measurement of anti-p53 antibodies in serum remains undisclosed. The aim of this study was to assess anti-p53 antibodies in the serum of patients with breast cancer, and correlate these results with various clinicopathologic parameters. Methods: We analyzed serum anti-p53 antibody levels in 124 patients with breast cancers and 7 patients with benign disease between April 2012 and March 2013, as well as levels of serum carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3. Results: Twenty-two of 124 patients with breast cancer had an increased concentration of anti-p53 antibodies. By distribution of …clinical stage, in stage 0–II the positive ratio of anti-p53 antibodies was significantly higher than that of CEA (p=0.03) and CA15-3 (p=0.01). There was a significant correlation between anti-p53 antibodies and family history (p=0.03). Triple-negative cancer also showed a significant correlation with anti-p53 antibodies (p=0.007). In patients with multiple and/or bilateral breast cancer, the level of anti-p53 was significantly higher than in unilateral breast cancer (62.5% vs 14.7%, p=0.004). Conclusion: Measurement of anti-p53 antibodies is useful for the prevention of oversight in the evaluation of multiple and/or bilateral breast cancer. Show more

Keywords: p53, breast cancer

DOI: 10.3233/CBM-140396

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 203-206, 2014

Authors: Lou, Emil | Johnson, Melissa | Sima, Camelia | Gonzalez-Espinoza, Rita | Fleisher, Martin | Kris, Mark G. | Azzoli, Christopher G.

Article Type: Research Article

Abstract: Background: Serum biomarkers are not in routine clinical use for diagnosis, prognosis, or treatment selection in lung cancer. Objective: We examined serum protein biomarkers from patients with metastatic lung cancer to determine whether they correlate with progression-free survival (PFS), overall survival (OS), or histologic subtype. Methods: Serum samples were collected prior to chemotherapy from 153 patients with metastatic lung cancer treated at Memorial Sloan-Kettering Cancer Center. Serum biomarkers were selected for ELISA testing based on their availability in a CLIA-certified clinical laboratory: ProGRP, SCC-Ag, NSE, CYFRA 21-1, TIMP1, and HE4. Pretreatment biomarker levels were correlated with …outcome using proportional hazards analysis and tumor histology using logistic regression analysis. Results: Univariate analysis indicated that only higher levels of CYFRA 21-1 were significantly associated with worsened PFS (HR 1.3, 95% CI 1.1–1.5, p< 0.01) and OS (HR 1.4, 95% CI 1.2–1.7, p< 0.001). Multivariate analysis of NSE, CYFRA 21-1, and TIMP1 indicated that CYFRA 21-1 remained independently associated with lower OS (HR 1.3, 95% CI 1.1–1.6, p< 0.01). Univariate analysis indicated that ProGRP (OR 3.3, 95% CI 1.7–6.5, p< 0.001) and NSE (OR 4.8, 95% CI 2.6–8.8, p< 0.0001) had the highest probabilities of differentiating SCLC from NSCLC. Multivariate analysis of these two markers demonstrated that they predicted SCLC histology with 94% accuracy. Univariate analysis showed that only SCCL-Ag distinguished squamous cell histology from adenocarcinoma (OR 4.4, 95% CI 1.7–11.5, p< 0.01). Conclusions: Serum CYFRA 21-1 may be useful in predicting patient survival, and serum ProGRP, NSE 21-1, and SCCL-Ag may be helpful in distinguishing between lung cancer sub-types. Show more

Keywords: Lung cancer, biomarkers, biomarker panel, CYFRA 21-1, SCCL-Ag

DOI: 10.3233/CBM-140399

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 207-214, 2014

Authors: Arrieta, Oscar | Pineda, Benjamín | Muñiz-Hernández, Saé | Flores, Diana | Ordóñez, Graciela | Borbolla-Escoboza, Jose R. | Orta, David

Article Type: Research Article

Abstract: Background: Few studies, have evaluated the prognostic impact of the quantification of mRNA expression levels in advanced non-small cell lung cancer (NSCLC). Objective: The aim of this work was to quantify mRNA expression levels in peripheral blood through three epithelial markers in patients with stages IIIB and IV in NSCLC. Methods: Seventy advanced NSCLC patients and ten healthy controls were included. All patients received platinum-based chemotherapy in first line treatment. Peripheral blood was obtained of each participant and mRNA expression levels present in circulating cells were quantified by molecular techniques (RT-PCR) using three epithelial markers: cytokeratin …(CK)-18, CK-19 and Carcinoembryonic-Antigen (CEA). The expression levels were quantified from a standard curve using the cDNA obtained from A549 cells. Registered in ClinicalTrials.gov (NCT01052818). Results: We found a significant statistical correlation between levels of CK-18, CK-19 and CEA mRNA. mRNA expression levels were lower in patients who present three or less metastasis; higher CEA mRNA expression was associated a worse progression-free survival to platinum-based chemotherapy and overall survival. Conclusion: RNA expression of CEA by RT-PCR is useful as a prognostic marker in advanced NSCLC. Show more

Keywords: Cytokeratins, carcinoembryonic-antigen, prognosis, lung cancer, circulating tumor cells

DOI: 10.3233/CBM-140394

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 215-223, 2014

Authors: Wang, Fen-Juan | Ding, Ye | Mao, Ying-Ying | Jing, Fang-Yuan | Zhang, Zhen-Yu | Jiang, Long-Fang | Guo, Jian-Feng | Sun, Xiang-Jue | Jin, Ming-Juan | Chen, Kun

Article Type: Research Article

Abstract: Background: Accumulated studies have suggested that single nucleotide polymorphisms (SNPs) in microRNAs are associated with risk of colorectal cancer (CRC). Objective: We tested our hypothesis that rs11014002 in hsa-miR-603 may be associated with CRC risk with a crosstalk of life-related factors. Methods: We conducted a case-control study which included 102 CRC patients and 204 matched cancer-free controls in Xiaoshan County. Results: We observed that subjects with rs11014002 CT/TT genotype had an increased susceptibility for CRC (CT vs. CC: odds ratio (OR)=2.352, 95% confidence interval (CI): 1.142–4.840, P=0.020; CT+TT vs. CC: OR=2.031, 95% CI: 1.063–3.883, …P=0.032). After stratification by lifestyle-related factors, similar results were found among nonsmokers (CT vs. CC: OR=2.753, 95% CI: 1.085–6.983, P=0.033; CT+TT vs. CC: OR=2.971, 95% CI: 1.188–7.435, P=0.020) and non-alcohol drinkers (CT+TT vs. CC: OR=3.279, 95% CI: 1.071–10.033, P=0.037). Conclusions: Our data suggest that hsa-miR-603 may be involved in colorectal tumorigenesis, and the genetic polymorphism in hsa-miR-603 is associated with CRC susceptibility. Show more

Keywords: hsa-miR-603, polymorphism, colorectal cancer, susceptibility

DOI: 10.3233/CBM-140395

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 225-231, 2014

Authors: Li, Xue-Mei | Su, Jing-Ran | Yan, Shi-Ping | Cheng, Zhao-Ling | Yang, Ting-Ting | Zhu, Qiang

Article Type: Research Article

Abstract: Aims: TIPE2 is a novel inflammation regulator, and the role of TIPE2 in colitis-induced colon cancer is not clear. The aim of this study was to test whether TIPE2 inhibits TLR4 pathway in colon cancer patients and to explore potential mechanism of TIPE2 in colon cancer by caspase-8. Methods: Expression of TIPE2 and TLR4 in human colon cancer tissues and cell line HT-29 was detected by immunohistochemistry or real-time PCR. TIPE2 mRNA was suppressed by siRNA transfection and the transfection efficiency was proved by fluorescence microscopy and real-time PCR. TLR4 pathway was activated by treating the cells with …1 μg/ml LPS for 4 h. Caspase-8 activities were tested by colorimetric assay in four HT-29 cell groups. Results: TIPE2 was expressed in the cytoplasm of colon cancer tissues and HT-29 cells. TIPE2 expression was more pronounced in colon cancer tissues compared to normal controls and it was related with lymph node metastasis and Dukes stage of colon cancer. TIPE2 expression was positively correlated with that of TLR4 in colon cancer (r=0.7354). TIPE2 expression was knocked down successfully by siRNA transfection. Caspase-8 activity was elevated both in TIPE2 knockdown cells and in TLR4 activated cells compared to wild-type cells (P< 0.05). And the caspase-8 activity was further increased in TIPE2 knockdown cells after TLR4 was activated (P < 0.05). Conclusion: TIPE2 can inhibit caspase-8 activity in colon cancer cells. TIPE2 can regulate TLR4 inflammatory effect and inhibit further amplification of cascade reaction via caspase-8, which provides one new therapeutic target for clinical treatment schedule. Show more

Keywords: TIPE2, TLR4, caspase-8, colon, tumorigenesis, colon, inflammation

DOI: 10.3233/CBM-140402

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 233-240, 2014

Authors: Gong, Jian | Zhang, Haili | Xing, Shushan | Li, Chunde | Ma, Zhenyu | Jia, Ge | Hu, Wanning

Article Type: Research Article

Abstract: Background: Adamantinomatous craniopharyngioma (ACP) is a benign but maldevelopmental tumor with a high recurrence rate. Objective: Theaim of this study was to investigate the dysregulated biological molecules that play important roles in the recurrence of ACP. Methods: We first performed microarray analysis on tumor samples from two pediatric patients with recurrent ACP and from two pediatric ACP patients without recurrence after a one-year follow-up. The expression of CXCL12 and CXCR4 in 45 specimens of pediatric ACP was further evaluated by immunohistochemistry. These results were correlated with the clinicopathological parameters and survival of the patients. …Results: Four downregulated genes (APC, ITGA, MCAM, and TIMP4) and 16 upregulated genes (CST7, CTSK, CTSL1, CXCL12, CXCR4, FN1, FXYD5, ITGB3, MMP2, MMP3, MMP7, MMP9, NR4A3, PLAUR, TIMP2, and VEGFA) were found in the recurrent patients. CXCL12 and CXCR4 were highly expressed in 13 patients (28.9%) and 14 patients (31.1%), respectively. High levels of CXCL12 and CXCR4 expression were significantly associated with a poor recurrence-free survival and were the prognostic factors for ACP recurrence in pediatric patients. Conclusions: High levels of CXCL12 and CXCR4 expression were associated with ACP recurrence. The role of CXCL12 and CXCR4 in the development of brain tumors requires further research. Show more

Keywords: Adamantinomatous craniopharyngioma, recurrence, CXCR4, CXCL12, Ki-67

DOI: 10.3233/CBM-140397

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 241-251, 2014

Authors: Can, Ozge | Erdemgil, Yigit | Yildirim, Zeynep Zulfiye | Ozduman, Koray | Pamir, M. Necmettin | Sav, Aydın | Ozpinar, Aysel

Article Type: Research Article

Abstract: Background: DR-70 is an immunoassay for fibrin and FDP in plasma and it has been shown useful in detection of over 14 different cancers. This study investigated the validity of the DR-70 test in gliomas as well as meningiomas. Methods: 77 brain tumor patients as well as 40 healthy individuals were prospectively included in the study and investigated using DR-70 kit. The glioma cohort of 33 patients consisted of 1, 11, 6 and 15 WHO grade 1, 2, 3 and 4 gliomas, respectively. The meningioma cohort of 44 patients contained 38, 5 and 1 WHO grade 1, 2 …and 3 tumors. Results: Test results were significantly higher than control values for both gliomas and meningiomas. The most balanced sensitivity and specificity values were obtained at cut-off level of 0.5 µg/ml FDP for both gliomas and meningiomas. Above this cutoff level the relative-risk for having a glioma was 5.1 times higher compared to controls with sensitivity and specificity of 76% and 85%, respectively. The relative-risk for meningioma was 5.8 with a sensitivity and specificity of 87% and 85%, respectively. Conclusion: FDP testing, which is a nonspecific cancer screening tool, is sensitive to the two most common primary brain malignancies, gliomas and meningiomas. Show more

Keywords: Meningioma, glioma, fibrin degradation products, DR-70

DOI: 10.3233/CBM-140400

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 253-258, 2014

Authors: Koyama, N.

Article Type: Research Article

Abstract: Background: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF) that provides a survival benefit to patients with non-small cell lung cancer (NSCLC). However, the treatment is sometimes accompanied by life-threatening bleeding events, and studies have not yet identified factors that can predict outcomes for NSCLC patients receiving bevacizumab. Methods: To identify prognostic factors for patients with NSCLC who are undergoing bevacizumab therapy, this study retrospectively investigated 34 consecutive patients with NSCLC treated with bevacizumab-containing chemotherapy. Results: Adverse cardiovascular events, including hypertension and bleeding events, during bevacizumab therapy were observed in 18 patients (53%). …Kaplan-Meier survival analyses and log-rank tests revealed that median overall survival was significantly better in patients who experienced adverse cardiovascular events than those who did not (442 versus 304 days; P=0.012). In the multivariate Cox proportional hazard model, the onset of adverse cardiovascular events was independently associated with a better overall survival. Conclusions: The onset of adverse cardiovascular events during bevacizumab therapy may be a favorable prognostic factor for patients with NSCLC. The results of this retrospective study warrant further large-scale prospective trials. Show more

Keywords: Adverse cardiovascular event, bevacizumab, non-small cell lung cancer, survival benefit, vascular endothelial growth factor

DOI: 10.3233/CBM-140404

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 259-265, 2014

Authors: Ma, Xuelei | Huang, Jingwen | Wu, Xin | Li, Xie | Zhang, Jing | Xue, Luqi | Li, Ping | Liu, Lei

Article Type: Research Article

Abstract: Background: Epidermal growth factor receptor (EGFR) has been reported to play a prognostic role in nasopharyngeal carcinoma (NPC). Nevertheless, the effect of EGFR predicting clinical outcomes is still controversial. Methods: Potentially eligible studies were retrieved using PubMed. Basic clinical characteristics of patients and statistical data were collected. Survival data can be got directly or could be calculated if it was available in other resources. Then, we used a meta-analysis model to review the correlation between over-expression of EGFR and survival outcome in NPC patients. Results: 15 eligible studies and 1225 patients were yielded in our meta-analysis. …The HRs with 95% confidence intervals (CIs) for OS and DFS/RFS/PFS were 2.11 [1.23, 3.60] and 2.17 [1.41, 3.35], respectively. Histological differentiation stage, race, different cut-off values and the percentage of TNM stage were divided for subgroup analysis. Conclusion: EGFR could be a fine prognostic factor of NPC, which might be proven by further multicenter clinical trials. Show more

Keywords: EGFR, nasopharyngeal carcinoma, meta-analysis, prognosis

DOI: 10.3233/CBM-140401

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 267-277, 2014

Authors: Xu, Weiping | Nan, Shuliang | Bai, Wenkun | Shen, E | Hu, Bing

Article Type: Research Article

Abstract: Background: Caveolin-1 is a major structural component of cell membrane invaginations. Over-expression of caveolin-1 is closely related to the tumorigenesis and progression of prostate cancer. Recently, contrast microbubbles in combination with ultrasound are being investigated for their therapeutic applications in tumor cells. However, the response of caveolin-1 after low-frequency ultrasound and SonoVue treatment in animal model is unclear. Objective: The goal of this study was to evaluate the effect of 80 kHz ultrasound and/or SonoVue on caveolin-1 expression and secretion in DU145 prostate tumors in nude mice. Methods: Six-week-old BALB/c male nude mice were subcutaneously injected …with DU145 cells in the right flank to establish a prostate cancer model, which were randomly divided into four groups (n=8 each): control group (sham-ultrasound exposure), SonoVue group, 80 kHz ultrasound group, 80 kHz ultrasound combined with SonoVue group. Tumor volumes and wet weights were measured, and the tumor volume curve was obtained as well. The mice were euthanized 21 days after treatment. Specimens of the tumor tissues were assessed the expression of caveolin-1 by immunohistochemistry and Western blot. The serum concentrations of caveolin-1 were detected by ELISA. Results: Treatment with ultrasound alone produced tumor volumes and weights reduction compared with control and SonoVue group. Combined ultrasound and SonoVue treatment produced greater tumor regression than either treatment alone (p < 0.05). Serum caveolin-1 concentrations were lower in the combination of ultrasound and SonoVue group than they were in control group (p =0.005), and had some certain correlation with tumor growth (wet weight) (r =0.507), although the difference was not statistically significant (p=0.199). Ultrasound alone treatment only slightly reduced the caveolin-1 concentrations in comparison with the control, and the difference was not statistically significant (p=0.125). The ultrasound-treated mice showed significant reduction in expression levels of caveolin-1 protein, compared with the control (p < 0.05). Levels of caveolin-1 were further reduced when combined with ultrasound and SonoVue as compared to the control (p < 0.01). Conclusions: Our results suggest that 80 kHz ultrasound have antitumor effect and the effect could be further strengthened by the combination of SonoVue. Down-regulating the expression of caveolin-1 is likely a potential biomarker of response to ultrasound and SonoVue treatment in prostate cancer mouse model. Show more

Keywords: Prostate cancer, low-frequency ultrasound, SonoVue, caveolin-1, biomarker

DOI: 10.3233/CBM-140405

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 279-286, 2014

Authors: Gao, Xueren | Zhang, Shulong | Qiao, Xiaoliang | Yao, Yao | Wang, Limin | Dong, Dong | Ma, Xinxiu | Wang, Taosheng

Article Type: Research Article

Abstract: Background: Associations between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49A/G polymorphism and cancer risk are inconclusive. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: A comprehensive literature search was performed using electronic databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: A total of 16,358 cases and 19,737 controls from 46 studies were included. Overall, significant association between CTLA-4 +49A/G polymorphism and cancer risk was observed in all genetic models (G vs. A: OR=0.88, 95%CI=0.83–0.93, P H …=0.000; GA vs. AA: OR=0.87, 95%CI=0.79–0.97, P H =0.000; GG vs. AA: OR=0.75, 95%CI= 0.65–0.86, P H =0.000; GG vs. GA+AA: OR=0.84, 95%CI=0.79–0.91, P H =0.001; GG+GA vs. AA: OR=0.83, 95%CI=0.74–0.92, P H =0.000). Stratified analysis by cancer type revealed that the CTLA-4+49A/G polymorphism is associated with the decreased risk of cervical cancer, breast cancer, lung cancer, HCC. Further subgroup analysis by ethnicity indicated that there was a statistically decreased cancer risk in Asian population. Conclusion: This meta-analysis suggests that CTLA-4+49A/G polymorphism is associated with cancer risk, especially in Asian population. Show more

Keywords: \CTLA-4, polymorphism, cancer risk, meta-analysis

DOI: 10.3233/CBM-140403

Citation: Cancer Biomarkers, vol. 14, no. 4, pp. 287-294, 2014