• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2093-2097
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• 2016

Background: HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. Aim of the work: The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. Materials and Methods: HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. Results: The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). Conclusions: HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1403-1407
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• 2015

Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1657-1663
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• 2015

Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

• Journal of Korean Neurosurgical Society
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• v.60 no.1
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• pp.21-29
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• 2017

Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

• Investigative Magnetic Resonance Imaging
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• v.26 no.1
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• pp.10-19
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• 2022

Purpose: To evaluate whether the added value of contrast leakage information from dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) is a better prognostic imaging biomarker than the cerebral blood volume (CBV) value in distinguishing true progression from pseudoprogression in glioblastoma patients. Materials and Methods: Forty-nine glioblastoma patients who had undergone MRI after concurrent chemoradiotherapy with temozolomide were enrolled in this retrospective study. Twenty features were extracted from the normalized relative CBV (nCBV) and extraction fraction (EF) map of the contrast-enhancing region in each patient. After univariable analysis, we used multivariable stepwise logistic regression analysis to identify significant predictors for differentiating between pseudoprogression and true progression. Receiver operating characteristic (ROC) analysis was employed to determine the best cutoff values for the nCBV and EF features. Finally, leave-one-out cross-validation was used to validate the best predictor in differentiating between true progression and pseudoprogression. Results: Multivariable stepwise logistic regression analysis showed that MGMT (O⁶-methylguanine-DNA methyltransferase) and EF max were independent differentiating variables (P = 0.004 and P = 0.02, respectively). ROC analysis yielded the best cutoff value of 95.75 for the EF max value for differentiating the two groups (sensitivity, 61%; specificity, 84.6%; AUC, 0.681 ± 0.08; 95% CI, 0.524-0.837; P = 0.03). In the leave-one-out cross-validation of the EF max value, the cross-validated values for predicting true progression and pseudoprogression accuracies were 69.4% and 71.4%, respectively. Conclusion: We demonstrated that contrast leakage information parameter from DSC MRI showed significance in differentiating true progression from pseudoprogression in glioblastoma patients.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• Journal of Life Science
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• v.34 no.6
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• pp.434-441
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• 2024

Mammary gland tumors are the most common tumors detected in non-spayed female dogs and pose a significant clinical challenge. Due to the strong similarity between canine mammary tumors (CMT) and human breast cancer (HBC), biomarkers identified in HBC can also be detected in CMT. These biomarkers have been shown to offer valuable insights into early diagnosis, prognosis, and treatment strategies. The purpose of this article is to provide a concise overview of CMT biomarkers based on the current literature. Traditional treatments for CMT in dogs typically begin with surgery, followed by chemotherapy, radiotherapy, or hormonal therapy. However, these treatments alone are not always fully effective. A diagnostic biomarker can detect the presence of a disease or the characteristics of a disease and classify an individual's status. Prognostic biomarkers focus on predicting the expected progression, recurrence, or survival of the disease in patients. By utilizing advances in understanding the mechanism of canine-specific mammary gland tumors, the estimation of biomarkers offers hope for improved outcomes in cancer patients. Novel technologies, such as single-cell RNA sequencing analysis, could provide a valuable resource for deciphering intra- and inter-tumoral heterogeneity. This review paper explores current research on CMT biomarkers and suggests directions for their development.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8311-8317
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• 2014

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, $P=7.3{\times}10^{-5}$), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, $Padj=1.1{\times}10^{-4}$). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, $P=1.0{\times}10^{-5}$) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.132-139
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• 2015

Recently, $p16^{INK4a}$/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the $p16^{INK4a}$/Ki-67 dual immunostaining using a CINtec$^{(R)}$ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of $p16^{INK4a}$ and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, $p16^{INK4a}$ and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of $p16^{INK4a}$/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the $p16^{INK4a}$/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.