Cancer Biomarkers - Volume 12, issue 1

Authors: Kashyap, Manoj Kumar | Pawar, Harsh A. | Keerthikumar, Shivakumar | Sharma, Jyoti | Goel, Renu | Mahmood, Riaz | Kumar, M. Vijaya | Kumar, K.V. Veerendra | Pandey, Akhilesh | Kumar, Rekha V. | Prasad, T.S. Keshava | Harsha, H.C.

Article Type: Research Article

Abstract: The pathogenesis of esophageal squamous cell carcinoma (ESCC) involves both genetic and environmental factors. Previously, we have carried out gene and protein expression profiling of ESCC using DNA microarrays and mass spectrometry-based quantitative proteomics, respectively. These studies resulted in identification of several potential biomarkers of ESCC, some with known reports of differential expression in the scientific literature and others that were novel observations from our studies. We report systematic validation of selected markers from our studies on a larger cohort of cancer tissue sections by immunohistochemical labeling of tissue microarrays. We have validated expression of insulin-like growth factor-binding protein 7 …(IGFBP7), stanniocalcin 2 (STC2), inhibin beta A (INHBA) and four and a half LIM domains 1 (FHL1). Immunohistochemical labeling with anti-stanniocalcin 2 antibody demonstrated its overexpression in 132/140 (94%) cases, IGFBP7 showed overexpression in 127/140 (91%) cases and overexpression of INHBA was observed in 62/105 (59%) of ESCC cases. In contrast, FHL1 expression was observed only in 12/143 (8%) of ESCC cases suggesting its possible involvement in tumor suppression. These data suggest that IGFBP7, INHBA, STC2 and FHL1 might play an important role in ESCC tumorigenesis, which can be explored in future studies. Overall, our findings open up new avenues for development of novel therapeutics and/or diagnostic approaches in ESCC. Show more

Keywords: Invasion, tumor suppression, esophageal adenocarcinoma, extracellular matrix

DOI: 10.3233/CBM-120289

Citation: Cancer Biomarkers, vol. 12, no. 1, pp. 1-9, 2013

Authors: Tang, Xiaokui | Yin, Xuedong | Xiang, Tingxiu | Li, Hongzhong | Li, Fan | Chen, Li | Ren, Guosheng

Article Type: Research Article

Abstract: Purpose: Protocadherin 10 (PCDH10), a homophilic cell adhesion member of the protocadherin family, plays important roles in calcium-dependent cell-cell adhesion and signal transduction. PCDH10 expression is downregulated in a number of different malignances, predominantly through promoter methylation-driven silencing. This study was designed to investigate PCDH10 expression and promoter methylation status in non-small cell lung cancer (NSCLC), and biological effects of PCDH10 in lung cancer cells. Methods: The mRNA levels and promoter methylation status of PCDH10 were examined by RT-PCR and methylation-specific PCR (MSP) in lung cancer cell lines as well as primary lung tissue samples, and the clinical …correlation of PCDH10 promoter methylation in NSCLC was further analyzed. The effects of PCDH10 re-expression in lung cancer cell lines was determined by cell proliferation, colony formation, and wound healing assays. Results: PCDH10 expression was downregulated or silenced in 4/8 lung cancer cell lines but could be restored by treatment with 5-aza-2’-deoxycytidine and trichostatin A. PCDH10 was also downregulated in NSCLC tissues compared to their corresponding adjacent tissues. Promoter methylation of PCDH10 was observed in 50% (20/40) of the NSCLC tissues but not in tumor-adjacent or normal tissues, and PCDH10 promoter methylation was statistically related to smoking. Ectopic expression of PCDH10 in silenced cells can reduce lung cancer cell proliferation and migration. Conclusion: PCDH10 is frequently downregulated by promoter methylation and may serve as a tumor suppressor gene (TSG) in NSCLC. Show more

Keywords: Protocadherin 10, promoter, methylation, non-small cell lung cancer

DOI: 10.3233/CBM-2012-00280

Citation: Cancer Biomarkers, vol. 12, no. 1, pp. 11-19, 2013

Authors: de Muga, Silvia | Hernández, Silvia | Salido, Marta | Lorenzo, Marta | Agell, Laia | Juanpere, Núria | Lorente, José A. | Serrano, Sergio | Lloreta, Josep

Article Type: Research Article

Abstract: The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n=44), ERG protein by IHC (n=84), and CXCR4 by quantitative RT-PCR (n=44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the …cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index=0.954). Seventy percent of Gleason ⩾ 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p=0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement. Show more

Keywords: CXCR4, TMPRSS2, ERG, rearrangement, overexpression, prostate cancer

DOI: 10.3233/CBM-2012-00288

Citation: Cancer Biomarkers, vol. 12, no. 1, pp. 21-30, 2013

Authors: Gao, Yuzhong | Wang, Jian | Fan, Guangyu

Article Type: Research Article

Abstract: NPRL2 is a tumor suppressor gene whose inactivation contributes to tumor development. However, NPRL2 expression in osteosarcoma remains unclear. This study aimed to assess NPRL2 expression in osteosarcoma and analyze its potential as a prognostic factor. NPRL2 expression in 48 cases of osteosarcoma and 40 cases of osteochondroma tumors was examined by immunohistochemistry. NPRL2 expression in 20 osteosarcoma and 20 osteochondroma specimens were detected by Real-time PCR and Western blot analysis. We found that 18 cases (37.5%) of osteosarcoma and 27 cases (67.5%) of osteochondroma showed positive NPRL2 expression. Real-Time PCR and Western blot analysis showed that NRPL2 expression was …lower in osteosarcoma than in osteochondroma (p< 0.05). The positive rate of NPRL2 expression was 71.4% (10/14), 25% (4/16) and 16.7% (3/18) in stage I, II and III of osteosarcoma, respectively. The positive rate of NPRL2 was 19% (4/21) and 48.1% (13/27) for low grade and high grade of osteosarcoma, respectively, with significant difference (p< 0.05). Cox multivariate analysis showed that the value of NPRL2 for predicting the overall survival of osteosarcoma patients. Despite the small size of the samples, our results suggest that NPRL2 expression is negatively related with the survival of osteosarcoma patients, indicating its value as a prognosis factor of osteosarcoma. Show more

Keywords: Osteosarcoma, NPRL2, immunohistochemistry, prognosis

DOI: 10.3233/CBM-120290

Citation: Cancer Biomarkers, vol. 12, no. 1, pp. 31-36, 2013

Authors: Shao, Ning | Jiang, Wen Yu | Qiao, Di | Zhang, Shi Ge | Wu, Ye | Zhang, Xiang Xiang | Hua, Li Xin | Ding, Yi | Feng, Ning Han

Article Type: Research Article

Abstract: Objective: Evidence is accumulating that several genes encoding DNA repair molecules may be cancer-susceptibility genes. Recently, SNPs in XRCC4, a member of DNA repair genes, have been implicated in altering the risk of various cancers. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation, we performed an updated meta-analysis. Methods: A comprehensive search was conducted to examine all the eligible studies about XRCC4 polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We included 31 studies …investigated 8 SNPs in XRCC4. Overall, our paper showed significant associations between the rs28360071, rs2075686 polymorphisms and cancer risk. In addition, significant association was maintained in prostate cancer (rs28360071), lung cancer (rs6869366) and bladder cancer (rs1805377) subgroups analysis. Conclusions: We conducted a systematic search and combined the available results in this meta-analysis, which provided evidence of the associations between SNPs in XRCC4 and cancer risk. The results suggested that rs28360071 polymorphisms were significantly associated with cancer risk. However, future studies are needed to investigate molecular mechanisms underlying the biological functions of XRCC4 SNPs in cancer development. Show more

Keywords: XRCC4, polymorphism, cancer risk

DOI: 10.3233/CBM-120292

Citation: Cancer Biomarkers, vol. 12, no. 1, pp. 37-47, 2013