Cancer Biomarkers - Volume 10, issue 3-4

Authors: Mearini, Luigi | Zucchi, Alessandro | Scarponi, Emanuele | Nunzi, Elisabetta | Aglietti, Maria Chiara | Bini, Vittorio | Porena, Massimo

Article Type: Research Article

Abstract: Introduction: Serum levels of Chromogranin A (CgA) were measured in consecutive patients with prostate diseases in order to evaluate the impact of age on CgA diagnostic significance. Materials and Methods: Serum levels of CgA were determinated in 217 consecutive patients immediately before prostate biopsy: CgA differences between cases (prostate cancer PC) and control (benign prostatic hyperplasia BPH) were analyzed, and CgA performance in prediction of PC was compared with age and standard diagnostic tools. CgA values were also analyzed in patients affected by PC, and compared with age and standard prognostic parameters. Results: At multivariate analysis, …CgA approaches a statistically significant value as independent predictor of PC and positively correlates with age. In PC group, CgA positively correlates with age, while no correlations are found with PSA, Gleason score or stage of disease. Conclusions: Age, correlating with CgA values in overall population and in PC subgroup, emerged as a confounding factor in CgA determination. Serum CgA has not been demonstrated as a diagnostic marker of PC being only a marker of neuroendocrine differentiation. Cga values did not correlate with other clinical prognostic factors, except age, in untreated-naive PC. Show more

Keywords: Chromogranin A, Prostate-specific antigen, serum marker, prostate cancer, diagnosis, prognosis

DOI: 10.3233/CBM-2012-0237

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 117-123, 2012

Authors: Gill, Kamaldeep | Mohanti, Bidhu Kalyan | Singh, Abhay Kumar | Mishra, Biswajit | Dey, Sharmistha

Article Type: Research Article

Abstract: The over expression of LL37, an antimicrobial peptide belonging~to the cathelicidin family has implication in the progression of human malignancy but the exact role is still not clear. This study aims to elucidate the correlation of LL37 with Head and Neck Squamous Cell Carcinoma (HNSCC) and the consequences of radiotherapy on it. The LL37 levels were quantified in serum samples of control and HNSCC patients at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance technology and ELISA. The LL37 of 50 HNSCC patients was significantly (p< 0.0001) threefold higher than the 25 controls and declined with respect …to radiation therapy (p< 0.0001) supporting its candidature as a prognostic marker in HNSCC. Show more

Keywords: LL37, HNSCC, radiation therapy, prognostic marker

DOI: 10.3233/CBM-2012-0238

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 125-134, 2012

Authors: Misawa, Kiyoshi | Kanazawa, Takeharu | Misawa, Yuki | Imai, Atsushi | Endo, Shiori | Hakamada, Katsura | Mineta, Hiroyuki

Article Type: Research Article

Abstract: Objectives: Collagen production plays a role in the development of tumors from cancer cells. The aim of the present study is to examine the involvement of epigenetic alteration of Collagen α 2 (I) (COL1A2) gene expression in cases of head and neck squamous cell carcinoma (HNSCC). Methods: COL1A2 expression was examined in a panel of cell lines using RT-PCR. The methylation status of the COL1A2 promoter was studied using bisulfate sequencing and methylation-specific PCR (MSP). Results: COL1A2 expression was absent in 6 of 11 (54.5%) UM-SCC cell lines, whereas three nonmalignant cell lines …had stable expressions. MSP analysis showed that 46/98 (46.9%) contained methylated alleles. COL1A2 methylation was significantly correlated with tumor size (P=0.041), lymph node status (P= 0.008), tumor stage (P=0.011), H-cadherin methylation (P=0.039) and disease-free survival (P=0.005). On multivariate Cox proportional hazard regression, which included age, sex, smoking status, and alcohol exposure, both tumor stage and COL1A2 methylation remained independent prognostic factors. Conclusions: This study suggests that CpG hypermethylation is a likely mechanism of COL1A2 gene inactivation, supporting the hypothesis that the COL1A2 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker. Show more

Keywords: COL1A2, DNA methylation, CpG island, head and neck cancer, 5-azacytidine

DOI: 10.3233/CBM-2012-0242

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 135-144, 2012

Authors: Bartling, Babett | Vanhooren, Valerie | Dewaele, Sylviane | Libert, Claude | Hofmann, Hans-Stefan | Haerting, Johannes | Nuding, Sebastian | Silber, Rolf-Edgar | Simm, Andreas | Chen, Cuiying Chitty

Article Type: Research Article

Abstract: Successful therapy of the non-small cell lung carcinoma (NSCLC) depends on its early detection, and non-invasive detection methods are preferred. As plasma proteins are modified by N-linked glycosylation, we tested the importance of the N-glycan profile in diagnosing and prognosticating NSCLC. We analysed desialylated plasma samples from 75 NSCLC patients, and 71 healthy individuals by the high-throughput DNA sequencer-based carbohydrate analytical profiling technique. We detected alterations in the levels of several N-glycans in NSCLC patients. Total α-1,6-core fucosylated biantennaries (NGA2F, NG1A2F, NA2F) and total bisecting α-1,6-core fucosylated biantennaries (NGA2FB, NA2FB) were reduced in NSCLC patients, whereas the branching α-1,3-fucosylated triantennary …N-glycan (NA3FB) was increased. Best diagnostic accuracy was identified for NG1A2F. NSCLC patients with TNM stage I stage did not show further differences, but patients with higher stages did (TNM II to IV). Those patients additionally had a reduced level in the α-1,6-core fucosylated structure NA2F with parallel increase in the non-fucosylated structure NA2. In this regard, NSCLC patients with a relatively low amount of NA2 per NA2F had a better three-year survival than patients with high amount. NSCLC patients show an altered N-glycan profile of plasma proteins that may be regarded as a supportive tool for cancer diagnosis. Show more

Keywords: Glycomics, N-glycan, non-small cell lung carcinoma, plasma, diagnosis

DOI: 10.3233/CBM-2012-0239

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 145-154, 2012

Authors: Ma, Shaohua | Shen, Luyan | Qian, Na | Chen, Keneng

Article Type: Research Article

Abstract: Objective: Amongst the current detections of tumor markers, measurement of serum tumor markers is the most convenient and the safest way. However, there are few promising serum tumor markers with confirmed prognostic value in NSCLC (non-small-cell lung cancer, NSCLC). Therefore, scientists only grafted the useful tumor markers, such as CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 which have been found in other solid tumors. However, previous reports about this issue remain controversial. This study is to analyze the prognostic values of these 6 markers in stage I NSCLC. Methods: One hundred and sixty four patients with stage I …NSCLC who underwent operation by single-surgery-team in Department I of Thoracic Surgery, Peking University Cancer Hospital between March 2000 and March 2011 were included. These patients had measurement of CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 using electrochemiluminescence immunoassay one week before operation. The relationship between the level of these 6 tumor markers and long term survival rate was analyzed. Results: The positive rate for CA125, CA19.9, NSE, SCC, CEA and CYFRA 21.1 in the 121 adenocarcinoma patients was 5.7%, 5.7%, 18.3%, 5.3%, 18.3%, and 20.7% respectively; whereas 3.1%, 2.6%, 23.8%, 26.8%, 14.0%, and 42.9% in 43 non-adenocarcinoma patients, respectively. In univariate analysis, the overall 5 year survival rate of patients with elevated CYFRA21.1 level was lower than that of patients with normal level in ADC subgroup (54.5% vs. 83.8%, p < 0.05) and in all 164 cases (49.5% vs. 76.4%, p < 0.05). In multivariate analysis, the level of CYFRA21.1 was an independent prognostic factor. But the other 5 markers didn’t show significant prognostic value. Conclusions: We found that the prognostic values of CA125, CA19.9, NSE, and SCC for stage I NSCLC are limited. CYFRA21.1 might be a hopeful prognostic serum tumor marker for stage I NSCLC. Show more

Keywords: Non-small-cell lung cancer, serum tumor markers, survival rate

DOI: 10.3233/CBM-2012-0246

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 155-162, 2012

Authors: Rosado, Leslie A. Rivera | Rodriguez-Canales, Jaime | Zhang, Baolin

Article Type: Research Article

Abstract: D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n=165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the …early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p< 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis. Show more

Keywords: D4-GDI, breast cancer, progression, immunohistochemistry

DOI: 10.3233/CBM-2012-0240

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 163-173, 2012

Authors: Yokomizo, Akira | Takakura, Michiko | Kanai, Yae | Sakuma, Tomohiro | Matsubara, Junichi | Honda, Kazufumi | Naito, Seiji | Yamada, Tesshi | Ono, Masaya

Article Type: Research Article

Abstract: Background: Early detection would be one of the most effective means to improve the outcome of renal cell carcinoma (RCC). We searched for a new plasma marker for RCC using a label-free quantitative shotgun proteomics method. Methods: Plasma proteins were digested by trypsin, and the resulting peptides were analyzed by 2-Dimensional Image Converted Analysis of Liquid chromatography mass spectrometry (2DICAL). An identified biomarker candidate was subjected to validation using the Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA). Results: Among a total of 23,407 independent MS peaks, we found that the mean intensity of 59 peaks significantly differed …between 20 clear cell RCC patients and 20 healthy controls. MS/MS spectra from 16 of the 59 peaks matched the amino acid sequences of the fibronectin 1 (FN1) gene product. The increased plasma level of FN1 in RCC patients was validated in a cohort of in 77 patients and 130 healthy controls (p<0.0001). Conclusions: The FN1 is considered to be a promising biomarker candidate for clear cell RCC. Furthermore, AlphaLISA is an alternate to the conventional enzyme-linked immunosorbent assay and should prove useful for the rapid validation of biomarker candidates. Show more

Keywords: Renal cell carcinoma, tumor marker, proteomics, fibronectin

DOI: 10.3233/CBM-2012-0243

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 175-183, 2012

Authors: Ramakrishnan, Valya | Kushwaha, Deepa | Koay, Debbie C. | Reddy, Hasini | Mao, Ying | Zhou, Liangfu | Ng, Kimberly | Zinn, Pascal | Carter, Bob | Chen, Clark C.

Article Type: Research Article

Abstract: Background: The DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) confers therapeutic resistance to DNA alkylating agents, including temozolomide. It is largely believed that MGMT promoter methylation is associated with down regulation of MGMT transcription and corresponding protein expression, thereby predisposing tumor cells to the toxic effect of temozolomide. Here we rigorously examined this underlying assumption. Methods: We examined the correlation between MGMT promoter methylation, transcription, and protein expression using The Cancer Genome Atlas (TCGA) glioblastoma database as well as an independent collection of glioblastoma specimens. Results: In both analyses, we …found that MGMT promoter methylation status correlates well with low MGMT mRNA levels (p=0.04). On the other hand, glioblastomas with unmethylated MGMT promoters exhibited a wide range of MGMT mRNA expression. Intriguingly, the MGMT mRNA levels correlated poorly with MGMT protein levels by Western blotting (R 2 = 0.04 , p=0.34) or by ImmunoHistoChemical (IHC) stain quantitation (R 2 = 0.02 , p=0.50). To exclude the possibility that the poor correlation was due to substandard specimens, we determined the mRNA and protein levels of Colony Stimulating Factor 1 (CSF1), a gene previously shown to exhibit excellent mRNA/protein correlation. In contrast to MGMT, the mRNA level of CSF1 correlated well with the protein level (R 2 = 0.47 , p=0.001). Importantly, long-term passaged glioblastoma cell lines with comparable MGMT transcript levels differed in MGMT protein levels, suggesting mechanisms of post-transcriptional regulation. Accordingly, the correlation between MGMT promoter methylation and MGMT protein expression was poor (p=0.27). In silico analysis predicted potential binding sites for several miRNA within the 3’UTR of MGMT, suggesting a mechanism for the post-transcriptional of MGMT. Conclusion: Our results suggest mechanisms such as miRNA mediated regulation for post-transcriptional regulation of MGMT. Identification of these mechanisms should enhance the value of MGMT based prognostic or predictive biomarker strategies. Show more

Keywords: Glioblastoma, TCGA, MGMT, methylation, therapeutic resistance, microRNA

DOI: 10.3233/CBM-2012-0245

Citation: Cancer Biomarkers, vol. 10, no. 3-4, pp. 185-193, 2012