• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3223-3228
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• 2013

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10917-10922
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• 2015

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$), alpha-fetoprotein (${\geq}100ng/ml$), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5073-5076
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• 2013

Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathological factors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patients who underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198 expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factor and its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher in patients with poor prognosis than those with good prognosis (P<0.05). Kaplan-Meier analysis results showed that the miR-198 expression level had a significant correlation with survival time (P=0.030) and that patients with a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed that patient prognosis (P=0.014), tumor length (P=0.040) and expression (P=0.012), and survival time had a significant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker for selection of cases requiring especial attention.

• Molecules and Cells
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• 제38권5호
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• pp.452-456
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• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• 생명과학회지
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• 제19권7호
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• pp.866-870
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• 2009

Fascin은 액틴결합 단백질로 형성을 포함한 많은 발생과정에 있어서 중요한 역할을 한다. Fascin은 암세포에 대한 생체표지인자로도 잘 알려져 있다. 그러나 이러한 fascin 유전자의 발현조절기전은 현재까지 잘 알려져있다. 그러나 이러한 fascin 유전자의 발현조절기전은 현재까지 잘 알려져 있지 않다. 본 연구에서는 Raf 돌연변이 초파리에서 이미 보고 되어있는 초파리 fascin 돌연변이 초파리의 휘어진 등털 표현형을 관찰함으로써 초파리 fascin 유전자의 발현이 Raf신호체계에 의해 조절되는 가를 조사하였다. RT-PCR과 Western blot의 실험 방법으로 Raf 유전자 돌연변이 초파리에서 fascin의 발현이 감소되어 있는 것을 확인하였으며, GAL4-UAS계로 Raf를 과발현시킨 초파리에서 fascin 발현이 증가하는 것을 확인할 수 있었다. 또한 세포의 증식과 이동 연구모델계로 잘 알려져 있는 초파리의 혈액세포에서 이러한 조절기전을 확인하였다. 이러한 결과들은 fascin유전자의 발현이 Raf 신호체계에 의해 조절된다는 것을 나타낸다.

• 치위생과학회지
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• 제21권1호
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• pp.45-51
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• 2021

Background: Periodontal disease, also known as gum disease, is a major dental inflammatory disease with a very high prevalence; it is the main cause of tooth loss. Therefore, diagnostic biomarkers that can monitor gum inflammation are important for oral healthcare. Since the gingival crevicular fluid (GCF) adequately reflects changes in the periodontal environment, they have become a target for the development of effective diagnostic biomarkers for periodontitis. In the present study, the level of the target molecules suggested as diagnostic biomarkers for periodontitis were analyzed in GCF samples collected from healthy individuals and periodontitis patients. In addition, useful targets for the diagnosis of periodontitis were evaluated. Methods: GCF samples were collected from healthy individuals and periodontitis patients using absorbent paper points. SDS-PAGE and Coomassie staining were performed for protein analysis. The protein concentrations of GCF specimens were determined using the Bradford method. The levels of the target molecules appropriate for diagnosing periodontal disease were measured by ELISA, according to the manufacturer's protocol. Results: The protein concentration of GCF collected from periodontitis patients was 3.72 fold higher than that in an equal volume of GCF collected from healthy individuals. ELISA analysis showed that the level of interukin-6 (IL-6), IL-8, metalloproteinases 2 (MMP-2), MMP-9, tumor necrosis factor-alpha (TNF-α), azurocidin, and odontogenic ameloblast-associated protein (ODAM) were higher in the GCF samples from the periodontitis patients than in those from the healthy individuals. However, the level of IL-6 and TNF-α were relatively low (> 5 pg/ml). The prostaglandin E2 (PGE2) levels were not significantly different between the two GCF samples. Conclusion: These results indicate that IL-8, MMP-2, MMP-9, azurocidin, and ODAM are potentially useful diagnostic biomarkers for periodontitis; combining multiple biomarkers will improve the diagnostic accuracy of periodontitis.

• Mass Spectrometry Letters
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• 제13권3호
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• pp.84-94
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• 2022

Neoadjuvant chemoradiotherapy (nCRT) is a standard therapy used for locally advanced rectal cancer prior to surgery, which can more effectively reduce the locoregional recurrence rate and radiation toxicity compared to postoperative chemoradiotherapy. The response of patients to nCRT varies, and thus, robust biomarkers for predicting a pathological complete response are necessary. This study aimed to identify possible biomarkers involved in the complete response/non-response of rectal cancer patients to nCRT. Comparative proteomic analysis was performed on rectal tissue samples before and after nCRT. Proteins were extracted for label-free proteomic analysis. Western blot and real-time PCR were performed using rectal cancer cell line SNU-503 and radiation-resistant rectal cancer cell line SNU-503R80Gy. A total of 135 up- and 93 down-regulated proteins were identified in the complete response group. Six possible biomarkers were selected to evaluate the expression of proteins and mRNA in SNU-503 and SNU-503R80Gy cell lines. Lyso-phosphatidylcholine acyltransferase 2, annexin A13, aldo-ketose reductase family 1 member B1, and cathelicidin antimicrobial peptide appeared to be potential biomarkers for predicting a pathological complete response to nCRT. This study identified differentially expressed proteins and some potential biomarkers in the complete response group, which would be further validated in future studies.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제25권5호
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• pp.396-405
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• 2022

Purpose: This study evaluated the predictive role of fecal calprotectin (FC) measured at an early stage of treatment for monitoring clinical remission (CR) after six months and endoscopic remission (ER) after one year of treatment in pediatric Crohn's disease (CD). Methods: This retrospective study included 45 patients who simultaneously underwent ileocolonoscopy and FC testing during follow-up. FC levels were measured before and after six weeks of treatment. CR was assessed after six months of treatment using Pediatric Crohn' s Disease Activity Index and acute-phase reactants. ER was assessed after one year using the Simple Endoscopic Score for Crohn's Disease. Results: Twenty-nine (64.4%) patients used oral prednisolone for remission induction and 16 (35.6%) patients used anti-tumor necrosis factor-alpha. Thirty (66.7%) patients achieved CR, while 24 (53.3%) achieved ER. The FC level measured after six weeks of treatment could predict CR (χ²=9.15, p=0.0025) and ER (χ²=12.31, p=0.0004). The δFC could predict CR (χ²=7.91, p=0.0049), but not ER (χ²=1.85, p=0.1738). With a threshold of ≤950.4 ㎍/g, FC at week six could predict CR with 76.7% sensitivity and 73.3% specificity. The area under the curve (AUC) was 0.769 (standard error 0.0773, p=0.0005). The same threshold predicted ER with 87.5% sensitivity and 71.4% specificity. The AUC was 0.774 (standard error 0.074, p=0.0002). Conclusion: FC assay at an early stage of treatment can be used as a surrogate marker to predict CR and mucosal healing in pediatric CD.

• 대한예방한의학회지
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• 제27권2호
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• pp.35-48
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• 2023

Objective : We studied prognostic biomarkers discovery for lung cancer based on the pattern identification for the personalized Korean medicine. Methods : Using 30 tissue samples, we performed a whole exome sequencing to examine the genetic differences among three groups. Results : The exome sequencing identified among 23,490 SNPs germline variants, 12 variants showed significant frequency differences between Xu and Stasis groups (P<0.0005). As similar, 18 and 10 variants were identified in analysis for Xu vs. Gentleness group and Stasis vs. Gentleness group, respectively (P<0.001). Our exome sequencing also found 8,792 lung cancer specific variants and among the groups identified 6, 34, and 12 variants which showed significant allele frequency differences in the comparison groups; Xu vs. Stasis, Xu vs. Gentleness group, and Stasis vs. Gentleness group. As a result of PCA analysis, in germline data set, Xu group was divided from other groups. Analysis using somatic variants also showed similar result. And in gene ontology analysis using pattern identification variants, we found genes like as FUT3, MYCBPAP, and ST5 were related to tumorigenicity, and tumor metastasis in comparison between Xu and Stasis. Other significant SNPs for two were responsible for eye morphogenesis and olfactory receptor activity. Classification of somatic pattern identification variants showed close relationship in multicellular organism reproduction, anion-anion antiporter activity, and GTPase regulator activity. Conclusions : Taken together, our study identified 40 variants in 29 genes in association with germline difference of pattern identification groups and 52 variants in 47 genes in somatic cancer tissues.

• IMMUNE NETWORK
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• 제20권3호
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• pp.27.1-27.11
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• 2020

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.