Cancer Biomarkers - Volume 10, issue 5

Authors: Tsaur, Igor | Noack, Anika | Waaga-Gasser, Ana Maria | Makarevic, Jasmina | Schmitt, Lars | Kurosch, Martin | Huesch, Tanja | Wiesner, Christoph | Wedel, Steffen | Bartsch, Georg | Ackermann, Hanns | Oppermann, Elsie | Lazariotou, Maria | Gasser, Martin | Haferkamp, Axel | Blaheta, Roman A.

Article Type: Research Article

Abstract: Background: Chemokines play a critical role in tumor initiation, progression, and metastasis and have been associated with poor prognosis in diverse malignancies. The prognostic impact of chemokines for renal cell cancer (RCC) remains to be defined. Methods: Patients diagnosed with RCC and operated between 07/07 and 05/11 were differentially assessed for expression profiles of a series of chemokines and their receptors by RT-qPCR and Western Blot analysis (tumor and adjacent normal tissue, n=37) and by Luminex for corresponding serum expression levels. Results were statistically correlated with clinicopathologic parameters. Results: Gene expression of CCL2, CCR7, CXCL12, CXCR3, …CXCR5 and CX3CL1 chemokines was significantly down-regulated in tumor compared to normal tissue. The gene profile for CCR6 was positively correlated with tumor size and stage. A positive linear correlation was found between CXCL12 and tumor stage as well as between CX3CR1 and C-reactive protein. In contrast to clear cell RCCs those of a chromophobe type showed a significantly down-regulated gene expression for CCR6, CCL20, and CXCL12. The CXCR7 serum level was significantly increased in patients with tumor-related mortality during postoperative follow-up. Conclusions: Chemokines may serve as novel diagnostic and prognostic biomarkers for RCC. Studies on larger collectives are required for further assessment of potential clinical application. Show more

Keywords: Chemokine, ligand, renal cell cancer, biomarker, diagnosis

DOI: 10.3233/CBM-2012-0247

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 195-204, 2012

Authors: Jeong, Pildu | Ha, Yun-Sok | Kim, Ji Sang | Cho, In-Chang | Kim, Won Tae | Kim, Yong-June | Yi Kim, Isaac | Yun, Seok-Joong | Lee, Sang-Cheol | Cha, Eun-Jong | Kim, Wun-Jae

Article Type: Research Article

Abstract: This study sought to determine if runt-related transcription factor 3 (RUNX3) methylation could accurately predict the overall survival in patients with muscle invasive bladder cancer (MIBC). Forty-seven patients with a longer followup period (cohort 1; reported previously) were analyzed. Tumor samples (cohort 2; newly collected) were obtained from 139 MIBC patients. The prognostic significance of RUNX3 methylation was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. RUNX3 methylation affected the overall survival in cohort 1 (log-rank test; P=0.030). Among the patients in cohort 2, RUNX3 promoter methylation was observed in 93 of the 139 tumor samples (66.9%). Kaplan-Meier …estimates showed a significant difference in overall survival according to RUNX3 methylation (P=0.020). By multivariate Cox regression analysis, positive RUNX3 methylation was an independent predictor of overall survival. These results suggest that RUNX3 promoter methylation is a significant prognostic factor for overall survival in MIBC patients. Show more

Keywords: Urinary bladder neoplasm, RUNX3, methylation, biologic tumor marker, prognosis

DOI: 10.3233/CBM-2012-0248

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 205-211, 2012

Authors: Antonacopoulou, Anna G. | Kottorou, Anastasia E. | Dimitrakopoulos, Fotinos-Ioannis D. | Triantafyllia, Vasiliki | Marousi, Stella | Koutras, Angelos | Kalofonos, Haralabos P.

Article Type: Research Article

Abstract: The vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis. VEGF levels appear to be influenced by single nucleotide polymorphisms (SNPs) of the VEGF gene. The aim of this study was to assess the importance of four VEGF SNPs in modulating susceptibility to colorectal cancer. We have genotyped 223 patients with colorectal cancer and 264 healthy individuals for the −2578C>A, −1498C>T, −634G>C and +936C>T VEGF SNPs using Taqman probes in polymerase chain reactions. The −2578 A, −1498 C and −634 G alleles were more frequently detected in CRC patients compared to healthy controls. Moreover, …the haplotype −2578C/−1498T was less frequent in CRC patients while the −2578A/−1498C haplotype was significantly more frequent in patients compared to healthy controls. VEGF −2578C>A and −1498C>T SNPs and −2578/−1498 haplotypes appear to be associated with susceptibility to CRC. Show more

Keywords: VEGF, colorectal cancer, single nucleotide polymorphisms

DOI: 10.3233/CBM-2012-0249

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 213-217, 2012

Authors: Ha, Seon-Ah | Lee, Youn Soo | Kim, Hyun Kee | Yoo, Jinah | Kim, Sanghee | Gong, Gi-Hwan | Lee, Youn Kyung | Kim, Jin Woo

Article Type: Research Article

Abstract: The differential expression profiling with breast normal and tumor tissues, and a breast cancer cell line led to identification of cytokeratin 18 (KT18) gene over-expressed in breast cancer. The expression pattern of KT18 in breast cancer was compared to those of conventional tumor markers such as proliferating cell nuclear antigen (PCNA) and minichromosome maintenance protein 3 (MCM3). Their expression patterns in breast cancer were almost identical, suggesting that KT18 might be useful for detection of proliferating fractions in the breast cancer. The immunohistochemical analyses on the tissue microarray consisting of invasive ductal carcinomas revealed that the up-regulation of KT18 is …observed in a majority of breast carcinomas whereas its down-regulation also occurs at a less frequency. Of particular interest, KT18 down-regulation was associated with histologically poorly differentiated carcinomas than well differentiated carcinomas. In addition, it was also significantly associated with the loss of estrogen receptor (ER) and progesterone receptor (PR), the prognostic markers of the breast cancer (P < 0.05), while not with HER2, tumor size, and lymph node metastasis. This result suggests that KT18 correlated with ER and PR may be utilized for the prognosis of breast cancer. Furthermore, the forced down-regulation of KT18 enhanced the growth of tumor xenografts in vivo and invasiveness in vitro. Therefore, our findings suggest that loss of KT18 expression might be a good indicator of the poor prognosis of the breast cancer and it may play an active role in the breast tumorigenesis. Show more

Keywords: Breast cancer, prognosis, biomarker, keratin 18 tumor differentiation steroid receptors

DOI: 10.3233/CBM-2012-0250

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 219-231, 2012

Authors: Xu, Qian | Yuan, Bibo | Xue, Fengxia | Zhang, Linqin | Li, Jie | Guo, Hualing | Yue, Tianfu

Article Type: Research Article

Abstract: Aim: To explore the possible association between Osteopontin (OPN) genetic polymorphisms and cervical cancer risk, which remains undocumented yet. Method: We enrolled 300 patients with histologically confirmed cervical squamous cell carcinoma and 774 age-matched healthy, unrelated, cancer-free female healthy subjects as control subjects. Three OPN gene polymorphisms were determined. Reulsts: The genotype distributions and allele frequencies of –156 GG/G and –443 T/C polymorphisms were significantly differed between cervical cancer patients and controls. The cervical cancer cases had markedly higher percentage of –156 GG carriage and significantly lower TT and TC of –443 genotypes than controls. The …Logistic regression analysis showed that the –156 GG carriage was associated with significantly elevated OR of 2.492 for cervical cancer while the TT and TC of –443 represented lower risks. This trend was not seen in subjects without human papillomavirus infections. In addition, the –156 GG carriages was significantly associated with poorer clinical conditions, including higher clinical stage, poorer tumor differentiation, higher positive lymph node status and higher chance of parametrical invasion. The –443 T/C and –66 T/G polymorphisms did not show any association with the clinicopathological feature. Conclusion: These results suggest that the –156 GG/G and –443T/C polymorphisms might be used as a genetic marker for cervical cancer susceptibility. Show more

Keywords: Polymorphisms, cervical cancer, risk, Osteopontin

DOI: 10.3233/CBM-2012-0251

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 233-239, 2012

Authors: Pereira, Lutécia H. Mateus | Adebisi, Islamiyat Nancy | Perez, Aymee | Wiebel, Michael | Reis, Isildinha | Duncan, Robert | Goodwin, W. Jarrard | Hu, Jennifer J. | Lokeshwar, Vinata B. | Franzmann, Elizabeth J.

Article Type: Research Article

Abstract: Background: Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease largely due to late stage diagnosis. Prior work indicates that soluble CD44 (solCD44) and total protein may be useful diagnostic markers for HNSCC. In this study we combine the markers solCD44, IL-8, HA, and total protein with demographic and risk factor data to derive a multivariate logistic model that improves HNSCC detection as compared to our previous data using biomarkers alone. Methods: We performed the solCD44, IL-8, HA, and total protein assays on oral rinses from 40 HNSCC patients and 39 controls using ELISA …assays. Controls had benign diseases of the upper aerodigestive tract and a history of tobacco or alcohol use. All subjects completed a questionnaire including demographic and risk factor data. Results: Depending on cancer subsite, differences between cases and controls were found for all markers. A multivariate logistic model including solCD44, total protein and variables related to smoking, oral health and education offered a significant improvement over the univariate models with an AUC of 0.853. Sensitivity ranged from 75–82.5% and specificity from 69.2âĂŞ82.1% depending on predictive probability cut points. Conclusion: A multivariate model, including simple and inexpensive molecular tests in combination with risk factors, results in a promising tool for distinguishing HNSCC patients from controls. Impact: In this case-control study, the resulting observations led to an unprecedented multivariate model that distinguished HNSCC cases from controls with better accuracy than the current gold standard which includes oral examination followed by tissue biopsy. Since the components are simple, noninvasive, and inexpensive to obtain, this model combining biomarkers, risk factor and demographic data serves as a promising prototype for future cancer detection tests. Show more

Keywords: CD44, hyaluronic acid, IL-8, protein, head and neck cancer

DOI: 10.3233/CBM-2012-0252

Citation: Cancer Biomarkers, vol. 10, no. 5, pp. 241-249, 2012