• Genomics & Informatics
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• 제7권4호
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• pp.195-202
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• 2009

BIRC5 (Survivin) belongs to the inhibitor of apoptosis gene family. The BIRC5 protein inhibits caspases and consequently blocks apoptosis. Thus, BIRC5 contributes to the progression of cancer allowing for continued cell proliferation and survival. In this study, we identified eight sequence variants of BIRC5 through direct DNA sequencing. Among the eight single nucleotide polymorphisms (SNPs), six common variants with frequencies higher than 0.05 were selected for larger-scale genotyping (n=1,066). Results of the study did not show any association between the promoter region polymorphisms and the clearance of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence. This is in line with a previous study in which polymorphisms in the promoter region does not influence the function of BIRC5. Initially, we were able to detect a signal with the ＋9194A>G, which disappeared after multiple corrections but led to a change in amino acid. Similarly, we were also able to detect an association signal between two haplotypes (haplotype-2 and haplotype-5) on the onset age of HCC and/or HCC occurrence, but the signals also disappeared after multiple corrections. As a result, we concluded that there was no association between BIRC5 polymorphisms and the clearance HBV infection and/or HCC occurrence. However, our results might useful to future studies.

• Genomics & Informatics
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• 제19권1호
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• pp.5.1-5.11
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• 2021

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

• Journal of Genetic Medicine
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• 제18권1호
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• pp.38-43
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• 2021

Purpose: Demand for genetic counseling on cancer predisposition syndrome is increasing. We evaluated the psychological effect on counselees after genetic counseling at a clinic in a single center. Materials and Methods: We surveyed a total of 72 enrolled participants who visited a genetic counseling clinic at the Samsung Medical Center (SMC). The initial survey was conducted before the first genetic counseling session, and the second survey was conducted after the second genetic counseling session. A total of 43 participants completed both the initial and second surveys. Results: The initial survey of 72 participants indicated higher feelings of guilt in the group with religion, higher depression and anxiety in the group with a diagnosis of self, and higher anxiety in the group on self-referral to the genetic counseling clinic. In the completed survey of 43 participants, overall decreased depression was observed after the second genetic counseling session (P=0.013). Risk perception and anxiety decreased in the group diagnosed with benign variant/variant of uncertain significance (BV/VUS, 25/3) and increased in the group diagnosed with pathogenic variant (PV, 15). Risk perception and anxiety differed between the BV/VUS and PV groups (P<0.001 and P=0.03, respectively). Conclusion: The genetic counseling clinic at the SMC was effective in ameliorating the depression score. Assessment of survey results revealed different depression scores, feelings of guilt and anxiety, and different effects of the genetic counseling clinic, depending on the subgroups. Understanding the needs and psychological characteristics of different groups is necessary for improving genetic counseling services.

• Genomics & Informatics
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• 제21권2호
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• pp.22.1-22.15
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• 2023

Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

• Genomics & Informatics
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• 제21권1호
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• pp.9.1-9.13
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• 2023

Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔG_binding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

• Journal of Genetic Medicine
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• 제7권1호
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• pp.67-77
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• 2010

목 적: 본 연구는 한국인 BRCA 유전자 돌연변이 가계구성원들을 대상으로 암진단 및 돌연변이 보유 여부가 심리 상태와 삶의 질에 미치는 영향을 알아보기 위해 시행되었다. 대상 및 방법: BRCA 유전자 돌연변이를 가진 13가계에서 암에 이환된 보인자 17명, 이환되지 않은 보인자 16명, 건강한 비보인자 13명이 본 연구의 분석에 포함되었다. 이 세 군을 대상으로 우울, 불안, 낙관, 유전성 유방암관련 지식수준과 삶의 질을 설문을 통하여 평가하였다. 결 과: 설문시기는 유전자 검사 후 평균 21개월(6-35)로 세 군 간의 차이는 없었다(P=0.254). 세 군 간의 우울, 낙관, 육체적 삶의 질은 유사했다. 불안은 세 군 모두에서 일반인 보다 상승되어 있었다. 이환된 보인자의 정신적 삶의 질은 암에 이환된 보인자가 다른 두 군에 비해 유의하게 낮았다(P=0.009, P=0.017). 다변량 분석 결과 정신적 삶의 질에 영향을 미친 인자는 암이환여부(P=0.043)와 직업유무(P=0.008) 였다. 결 론: 같은 돌연변이 가계 내에서 돌연변이 유무는 우울, 불안, 낙관에서 심리적반작용을 일으키지 않았으나, 돌연변이 가계 구성원의 불안 수준은 돌연변이 유무에 관계 없이 높았다. 본 연구는 소규모 표본을 대상으로 한 단면적 연구이나, BRCA 유전자 검사에 수반될 수 있는 심리적 스트레스 및 그에 대한 대처법을 수립하는 데 기초연구로 의의를 가진다.

• Journal of Genetic Medicine
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• 제8권2호
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• pp.105-112
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• 2011

목적: 유전성 유방암 가계에서 BRCA 유전자 돌연변이 결과 공유의 중요성은 가족검사를 통해 돌연변이 보인자를 확인하고 적극적인 암 발생 감시와 예방적 치료를 제공하는데 있다. 본 연구를 통하여 유전성 유방암 가계에서 돌연변이 사실에 대한 공유 정도, 등친 별 의사소통 차이와 이에 영향을 미치는 요인을 확인하고자 한다. 대상 및 방법: 한국인 유전성유방암 연구에 등록되어 BRCA1 또는 BRCA2 돌연변이가 확인된 발단자 106명을 대상으로 검사 후 유전상담, 유전성 유방암 지식도 평가, 돌연변이 사실에 대한 가족간의 의사소통 과정, 가족 검사 현황에 대해 설문조사를 시행하였다. 결과: 최종 응답자 106명 중 99명은 적어도 한 명 이상의 친족에게 자신의 유전자 검사결과를 알렸으며, 일등친 가족에게만 알린 경우는 68.7%, 일등친과 이등친 이상의 가족에게 돌연변이 사실을 알린 경우는 31.3%였다. 단변량 분석결과 일등친 가족에게만 검사결과를 알린 군이 이등친 또는 삼등친 가족에게 돌연변이 사실을 알린 군에 비해 기혼자의 비율이 더 높았으며, 검사 후 유전상담일로부터 설문조사 시점까지 기간이 유의하게 짧은 것으로 나타났다. 가족에게 돌연변이 사실을 알린 이유에 대해서는 가족들에게 BRCA 유전자 돌연변이 가능성과 유방암 발병위험성을 알리기 위함에 가장 큰 비중을 차지하였다. 결론: 유전성 유방암 가계에서 BRCA 돌연변이 사실에 대한 정보를 보다 많은 가족과 공유하기 위해서는 유전상담 시 환자 개개인의 가계 구조를 파악하여 차별화된 의사소통 방법을 제시해 주어야 할 것이다.

• 대한임상검사과학회지
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• 제49권2호
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• pp.79-87
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• 2017

GenesWell$^{TM}$ BCT는 호르몬 수용체 양성, HER2 음성, 및 pN0 또는 1인 조기 유방암 환자의 10년내 타 장기 전이 재발 위험도를 제시하는 다지표 예후 예측 검사로, 예후에 대한 위험을 BCT Score로 제시한다. 본 연구에서는 GenesWell$^{TM}$ BCT의 분석적 성능을 검사하였다. 조기 유방암 환자의 FFPE 검체로 부터 추출한 RNA를 대상으로 GenesWell$^{TM}$ BCT 수행하여, 12개 유전자의 발현값을 측정하였다. GenesWell$^{TM}$ BCT의 최소검출한계, 공란 한계 및 측정 범위는 단계 희석한 RNA 검체를 사용하여 평가하였으며, 분석적 정밀도 및 특이도 시험은 BCT Score에 따라 저위험군, 고위험군 그리고 경계선 주변으로 나누어진 3개의 RNA 검체를 이용하여 시험하였다. GenesWell$^{TM}$ BCT는 $1ng/{\mu}L$ 미만의 RNA 검체에서 RNA를 측정할 수 있었으며, 다기관에서 수행된 분석적 정밀도 시험에서 반복성 100% 및 재현성 98.3%의 결과를 확인할 수 있었다. 또한, 분석적 특이도 시험을 통해, 간섭 물질이 검체의 재발 위험성 판정에 영향을 미치지 않음을 확인할 수 있었다. 이들 결과는 GenesWell$^{TM}$ BCT가 95% 이상의 항상성을 나타내는 높은 분석적 성능을 가지고 있음을 제시한다.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2003년도 제2차 연례학술대회 발표논문집
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• pp.66-72
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• 2003

Toxicogenomics is now emerging as one of the most important genomics application because the toxicity test based on gene expression profiles is expected more precise and efficient than current histopathological approach in pre-clinical phase. One of the challenging points in Toxicogenomics is the construction of intelligent database management system which can deal with very heterogeneous and complex data from many different experimental and information sources. Here we present a new Toxicogenomics database developed as a part of 'Toxicogenomics for Efficient Safety Test (TEST) project'. The TEST database is especially focused on the connectivity of heterogeneous data and intelligent query system which enables users to get inspiration from the complex data sets. The database deals with four kinds of information; compound information, histopathological information, gene expression information, and annotation information. Currently, TEST database has Toxicogenomics information fer 12 molecules with 4 efficacy classes; anti cancer, antibiotic, hypotension, and gastric ulcer. Users can easily access all kinds of detailed information about there compounds and simultaneously, users can also check the confidence of retrieved information by browsing the quality of experimental data and toxicity grade of gene generated from our toxicology annotation system. Intelligent query system is designed for multiple comparisons of experimental data because the comparison of experimental data according to histopathological toxicity, compounds, efficacy, and individual variation is crucial to find common genetic characteristics .Our presented system can be a good information source for the study of toxicology mechanism in the genome-wide level and also can be utilized fur the design of toxicity test chip.

• Journal of Preventive Medicine and Public Health
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• 제41권6호
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• pp.373-379
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• 2008

Objectives ; The objective of this study was to evaluate the prevalence of atrophic gastritis and intestinal metaplasia according to gender, age and Helicobacter pylori infection in a rural population in Korea. Methods: Between April 2003 and January 2007, 713 subjects (298 men and 415 women, age range: 18-85) among the 2,161 adults who participated in a population-based survey received gastrointestinal endoscopy. All the subjects provided informed consent. Multiple biopsy specimens were evaluated for the presence of atrophic gastritis and intestinal metaplasia. The presence of Helicobacter Pylori was determined using CLO and histology testing. Results ; The age-adjusted prevalence of atrophic gastritis was 42.7% for men and 38.1% for women and the prevalence of intestinal metaplasia was 42.5% for men and 32.7% for women. The prevalence of atrophic gastritis and intestinal metaplasia increased significantly with age for both men and women (p for trend<0.001). The age-adjusted prevalence of Helicobacter pylori was similar for men (59.0%) and women (56.7%). The subjects with Helicobacter pylori infection showed a significantly higher prevalence of intestinal metaplasia (44.3%) compared with that (26.8%) of the noninfected subjects (p<0.001). However, the prevalence of atrophic gastritis was not statistically different between the Helicobacter pylori-infected subjects and the noninfected individuals. Conclusions : Our findings suggest that the prevalence of atrophic gastritis and intestinal metaplasia is higher for a Korean rural population than that for a Western population; this may be related to the high incidence of gastric cancer in Koreans. Especially, the prevalence of intestinal metaplasia was high for the subjects with Helicobacter pylori infection. The multistep process of gastric carcinogenesis and the various factors contributing to each step of this process need to be determined by conducting future follow-up studies.