• Tuberculosis and Respiratory Diseases
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• 제71권1호
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• pp.8-14
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• 2011

Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6599-6603
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• 2015

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2819-2826
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• 2015

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-${\alpha}$-acetyltransferase 10 protein (Naa10p), synuclein-${\gamma}$ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3-subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6015-6020
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• 2014

Background: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. Materials and Methods: Initial literature was identified using Medline and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). Results: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00-1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post-treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). Conclusions: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7031-7038
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• 2015

Background: Arginine may play important roles in tumor progression by providing ornithine for polyamine biosynthesis, required for cell growth. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Materials and Methods: The expressions of arginase isoforms (ARG1 and ARG2), ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) were examined in fifty paired HNSCC and adjacent non-tumor tissues by immunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitative real-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patients and hundred controls. Results: ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODC was significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with no difference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation with qPCR showed 6.23 fold increase in HNSCC. Conclusions: These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4707-4712
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• 2012

Annexin A1 is a 37-kDa calcium- and phospholipid-binding protein of the annexin superfamily considered to play an important role in tumorigenesis. However, associations with clinicopathological features in pancreatic ductal adenocarcinoma (PDAC) cases have yet to be fully defined. We therefore investigated the prognostic value of annexin A1 protein as a PDAC biomarker in 83 tumor and matched non-cancerous tissues or normal pancreas tissues. Expression was analyzed using real-time RT-PCR, Western blotting and immunohistochemistry. In non-tumor tissue, myoepithelial cells showed no or weak expression of annexin A1 while expression was strong and sometimes even located in the nuclei of endothelial cells in tumor tissue. High expression was significantly associated with advanced stage (P <0.05) and a worse overall survival (P <0.05). These results provide new insights to better understand the role of annexin A1 in PDAC survival, and might be relevant to prediction of prognosis and development of more effective therapeutic strategies aimed at improving survival.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2699-2703
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• 2016

Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. Aim: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. Materials and Methods: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 $treatment-na{\ddot{i}}ve$ chronic HCV, 25 post-HCV compensated cirrhosis and 23 $treatment-na{\ddot{i}}ve$ HCC cases). Results: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (P<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. Conclusions: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC.

• Journal of Ginseng Research
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• 제35권3호
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• pp.339-343
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• 2011

Polycyclic aromatic hydrocarbons (PAHs) are well known environmental carcinogens. PAH metabolites, especially BaP-7,8- dihydrodiol, 9,10 epoxide, initiate carcinogenesis via high specificity binding to DNA to form DNA adducts. The Korean red ginseng (KRG) from Panax ginseng has been suggested to protect against damages due to PAH exposure but the mechanism is unknown. Therefore, we investigated effects of KRG on PAH exposure using toxicokinetic methods and changes of PAH-induced oxidative damage during a 2 week-clinical trial (n=21 healthy young female, $23.71{\pm}2.43$ years). To analyze antioxidative effects of KRG, we measured changes in the levels of urinary malondialdehyde (MDA) before and after KRG treatment. We observed a significant positive association between levels of urinary MDA and 1-hydroxypyrene, a biomarker of PAH exposures (slope=1.47, p=0.03) and confirmed oxidative stress induced by PAH exposures. A reverse significant correlation between KRG treatment and level of urinary MDA was observed (p=0.03). In summary, results of our clinical trial study suggest that KRG plays a significant role in antioxidative as well as toxicokinetic pathways against PAHs exposure.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3547-3553
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• 2014

Background: The prognostic value of serum alkaline phosphatase (S-ALP) has not been fully validated for nasopharyngeal carcinoma (NPC). Materials and Methods: S-ALP levels were measured in 601 patients newly diagnosed with NPC before radical treatment, and possible associations of these levels with 5-year overall survival (OS) and tumor-free survival (TFS) were explored using univariate and multivariate analyses. Results: Elevated pretreatment S-ALP (>85 U/L) was significantly less frequent among patients classified as T1+2 or stage I+II than among those classified as T3+4 or stage III+IV. Multivariate analysis showed that elevated pretreatment S-ALP (>85 U/L), age, T classification and N stage were independent predictors of poor OS and TFS. Conclusions: Pretreatment S-ALP may be a reliable biomarker to evaluate the long-term prognosis of patients with NPC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4595-4598
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• 2013

We conducted a comprehensive study to investigate the role of genes involved in transport pathways in response to chemotherapy and clinical outcome of osteosarcoma cases. Genotyping of six SNPs was performed in a 384-well plate format on the Sequenom MassARRAY platform for 208 osteosarcoma patients to reveal any correlations of the six SNPs with response to chemotherapy and clinical outcome. Individuals with the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes had a higher probability of responding poorly to chemotherapy, indicated by odds ratios (ORs) of 2.46 (95%CI, 1.21-5.74) and 3.78 (95% CI, 1.20-13.85), respectively. Moreover, the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes were significantly associated with shorter diseasefree survival (DFS) and overall survival (OS). Our study found the two SNPs in two transporter genes and one phase II metabolism enzyme to be associated with response to chemotherapy and overall survival in osteosarcoma patients, suggesting potential prognostic biomarker applications of the two SNPs.