편스플라인 추정량의 편의에 대한 점근 정규성

추인선,최재룡 한국통계학회 2000 응용통계연구 Vol.13 No.2

비모수 회귀모형에 있어서 평활스플라인에 대하여 언급하고, 그 간단한 성질을 다룬다. 선형회귀나 다항식회귀에서는 적합하기 나쁜 데이터가 많이 존재한다. 설명변수가 여러 개인 경우에 준모수 회귀모형은 하나 혹은 그 이상의 변수에 대해서는 비모수 함수를 다른 변수에 대하서는 선형함수를 적합시켜 그들의 가법성을 가정한 것이다. 준모수 회귀모형에 있어서 선형부분의 회귀계수의 추정량에 편의가 발생하고, 여기서는 그 편의에 대한 점근 정규성을 다룬다 In this paper, we describes smoothing spline in nonparametric regression and some asymptotic results for estimates of the regression cofficients in the parametric part were biased on semi parametric regression estimator.

New Concepts for Diagnosis and Prognosis of HCC : Discovering Prognostic Subtypes of HCC using Gene Expression Profiling

추인선 ( In Sun Chu ) 대한간암연구회 2006 대한간암연구회 학술심포지엄 Vol.9 No.-

A gene expression signature of FOXM1 predicts the prognosis of hepatocellular carcinoma

송빛나,추인선 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

FOXM1 (Forkhead box M1) is a key regulator of tumorigenesis. Previous studies demonstrated that FOXM1 overexpression was strongly correlated with poor prognosis in various cancers, including hepatocellular carcinoma (HCC). In this study, we examined an association between the gene expression signature of FOXM1 and HCC patient outcome. The co-expressed gene set of FOXM1, which is significantly associated with the prognosis of HCC patients, was identified by analyzing the gene expression profiles of 100 patients with HCC, and this gene set was validated in two independent HCC patient cohorts (n=573). In multivariate analysis, the co-expressed gene set of FOXM1 was the most significant prognostic factor for overall survival in patients with HCC (hazard ratio=1.706, 95% confidence intervals=1.176–2.475, P=0.005). We also analyzed different types of cancer, including pancreatic adenocarcinoma, lung adenocarcinoma, breast carcinoma and bladder urothelial carcinoma, to verify the association between the co-expressed gene set of FOXM1 and patient prognosis, and we found a consistent prognostic significance, regardless of tumor type. Finally, we identified a putative signaling pathway in which miR-34a acts as an upstream regulator of the FOXM1-MYC signaling network; this pathway may be ultimately responsible for the poor prognosis of HCC patients. The prognostic subgroups defined by the gene expression signature of FOXM1 could help predict high-risk patients and may guide selection of the best treatment strategy.

Bioinformatics Resources of the Korean Bioinformation Center (KOBIC)

이병욱,추인선,김남신,이진혁,김선영,김완규,이상혁 한국유전체학회 2010 Genomics & informatics Vol.8 No.4

The Korean Bioinformation Center (KOBIC) is a national bioinformatics research center in Korea. We developed many bioinformatics algorithms and applications to facilitate the biological interpretation of OMICS data. Here we present an introduction to major bioinformatics resources of databases and tools developed at KOBIC. These resources are classified into three main fields: genome, proteome, and literature. In the genomic resources, we constructed several pipelines for next generation sequencing (NGS) data processing and developed analysis algorithms and web-based database servers including miRGator, ESTpass, and CleanEST. We also built integrated databases and servers for microarray expression data such as MDCDP. As for the proteome data, VnD database, WDAC, Localizome, and CHARMM_HM web servers are available for various purposes. We constructed IntoPub server and Patome database in the literature field. We continue constructing and maintaining the bioinformatics infrastructure and developing algorithms.

A Database of Gene Expression Profiles of Korean Cancer Genome

김선규,추인선 한국유전체학회 2015 Genomics & informatics Vol.13 No.3

Because there are clear molecular differences entailing different treatment effectiveness between Korean and non-Korean cancer patients, identifying distinct molecular characteristics of Korean cancers is profoundly important. Here, we report a web-based data repository, namely Korean Cancer Genome Database (KCGD), for searching gene signatures associated with Korean cancer patients. Currently, a total of 1,403 cancer genomics data were collected, processed and stored in our repository, an ever-growing database. We incorporated most widely used statistical survival analysis methods including the Cox proportional hazard model, log-rank test and Kaplan-Meier plot to provide instant significance estimation for searched molecules. As an initial repository with the aim of Korean-specific marker detection, KCGD would be a promising web application for users without bioinformatics expertise to identify significant factors associated with cancer in Korean.

차세대 시퀀싱 기술의 활용

김남신,추인선 한국생화학분자생물학회 (구 한국생화학회) 2009 생화학분자생물학회 소식 Vol.29 No.4

A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

윤세련,노윤길,추인선,허정훈,김승일,장희경,강태홍,정진웅,고상석,Vladimir Larionov,임선희 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case–control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02–4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer.

Bioinformatic identification of prognostic signature defined by copy number alteration and expression of CCNE1 in non-muscle invasive bladder cancer

송빛나,김선규,추인선 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Non-muscle invasive bladder cancer (NMIBC) patients frequently fail to respond to treatment and experience disease progression because of their clinical and biological diversity. In this study, we identify a prognostic molecular signature for predicting the heterogeneity of NMIBC by using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profiles of 404 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. Of the 14 molecules with significant copy number alterations that were previously reported, 13 were significantly correlated with copy number and expression changes. Prognostic gene sets based on the 13 genes were developed, and their prognostic values were verified in three independent patient cohorts (n=501). Among them, a signature of CCNE1 and its coexpressed genes was significantly associated with disease progression and validated in the independent cohorts. The CCNE1 signature was an independent risk factor based on the result of a multivariate analysis (hazard ratio=6.849, 95% confidence interval=1.613–29.092, P=0.009). Finally, gene network and upstream regulator analyses revealed that NMIBC progression is potentially mediated by CCND1-CCNE1-SP1 pathways. The prognostic molecular signature defined by copy number and expression changes of CCNE1 suggests a novel diagnostic tool for predicting the likelihood of NMIBC progression.

Novel genes implicating tumor progression & suppression of HCC through CpG island methylation

이효준,김용훈,임태진,임선희,추인선,강구정 대한외과학회 2009 대한외과학회 학술대회 초록집 Vol.2009 No.11

Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence

박승진,강예은,김정환,박종열,김선규,백승우,추인선,이신애,이성은,박영주,정은재,김진만,고혜미,김재룡,정승남,원호륜,장재원,구본석,김선영 대한이비인후과학회 2022 Clinical and Experimental Otorhinolaryngology Vol.15 No.2

Objectives. Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods. This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results. Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion. We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer