데이터 중심 디지털 헬스케어

손대순 한국융합과학회 2022 한국융합과학회 춘계 학술세미나집 Vol.2022 No.0

Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer

박일현,손대순,최윤라,최지현,박지은,전영정,조민섭,김홍관,최용수,심영목,강정희,박수지,이진선,김성현,이병철,김진국 대한암학회 2024 Cancer Research and Treatment Vol.56 No.1

Purpose Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. Materials and Methods In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. Results The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. Conclusion The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Temporal Change in the Use of Laboratory and Imaging Tests in One Week Before Death, 2006–2015

김현아,조민섭,손대순 대한의학회 2023 Journal of Korean medical science Vol.38 No.12

Background: To analyze the trends in laboratory and imaging test use 1 week before death among decedents who died in Korean hospitals, tests used per decedents from 2006 to 2015 were examined by using the National Health Insurance Service-Elderly Sample Cohort (NHISESC) dataset. Methods: The study population consisted of decedents aged ≥ 60 years old with a history of admission and death at a hospital, and tests recorded in the payment claims for laboratory and imaging tests according to the Healthcare Common Procedure Coding System codes were examined. Twenty-eight laboratory and 6 imaging tests were selected. For each year, crude rates of test use per decedents in each age and sex stratum were calculated. Regression analysis was used to examine the temporal changes in the test use. Results: During the follow-up period, 6,638 subjects included in the sample cohort died. The number of total laboratory and imaging tests performed on the deceased increased steadily throughout the study year from 10.3 tests/deceased in 2006 to 16.6 tests/deceased in 2015. The use of tests increased significantly in general hospitals, however, not in nursing hospitals. Laboratory tests showed yearly increase, from 9.46/deceased in 2006 to 15.57/ deceased in 2015, an annual increase of 7.39%. On the other hand, the use of imaging increased from 0.86/deceased in 2006 to 1.01/deceased in 2015, which was not statistically significant. Conclusion: The use of tests, especially laboratory tests, increased steadily over the years even among those elderly patients at imminent death. Reducing acute healthcare at the end of life would be one target not only to support the sustainability of the health care budget but also to improve the quality of dying and death.

Predicting Recurrence Using the Clinical Factors of Patients with Non-small Cell Lung Cancer After Curative Resection

이현주,조지석,손대순,이진선,최용수,김관민,심영목,김진국 대한의학회 2009 Journal of Korean medical science Vol.24 No.5

We present a recurrence prediction model using multiple clinical parameters in patients surgically treated for non-small cell lung cancer. Among 1,578 lung cancer patients who underwent complete resection, we compared the early-recurrence group with the 3-yr non-recurrence group for evaluating those factors that influence early recurrence within one year after surgery. Adenocarcinoma and squamous cell carcinoma were analyzed independently. We used multiple logistic regression analysis to identify the independent clinical predictors of recurrence and Cox’s proportional hazard regression method to develop a clinical prediction model. We randomly divided our patients into the training and test subsets. The pathologic stages, tumor cell type, differentiation of tumor, neoadjuvant therapy and age were significant factors on the multivariable analysis. We constructed the model for the training set with adenocarcinoma (n=236) and squamous cell carcinoma (n=305), and we applied it to the test set with adenocarcinoma (n=110) and squamous cell carcinoma (n=154). It was predictive for the in adenocarcinoma (P<0.001) and the squamous cell carcinoma (P=0.037), respectively. Our results showed that our recurrence prediction model based on the clinical parameters could significantly predict the individual patients who were at high risk or low risk for recurrence.

제1기 비소세포폐암 환자의 수술적 절제 후 Matrix Metalloproteinase-2 활성도에 따른 재발 및 예후

김상희,홍영숙,이진선,손대순,임유성,송인승,이혜숙,김도훈,김진국,최용수 대한흉부외과학회 2005 Journal of Chest Surgery (J Chest Surg) Vol.38 No.1

Background: Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC. 배경: 기질금속단백분해효소-2 (MMP-2)는 기저막과 세포 외 기질의 분해에 작용하여 악성종양의 국소침윤 및 원격전이에 중요한 역할을 담당한다. 본 연구는 수술적인 절제를 시행 받은 제1기 비소세포폐암에서 MMP-2의 활성도를 측정하고 예후인자로서의 의미를 분석하고자 하였다. 대상 및 방법: 수술 전 방사선 또는 항암제 요법을 시행하지 않은 병리학적 제1기 비소세포폐암 환자 34명을 대상으로 하였다. 폐엽 절제 조직에서 종양 조직과 비종양 조직의 단백질을 각각 추출하여 젤라틴-기질-단백분해효소 분석법을 시행하였다. 결과: MMP-2 활성도는 비종양 조직보다 종양 조직에서 높았다. 종양 조직, 비종양 조직 모두에서 비재발군에 비해 재발군의 MMP-2 활성도가 높았으나 비종양 조직에서의 차이가 통계적 유의성이 있었다(p<0.01). 생존율 분석에서도 MMP-2 활성도가 높을 경우 불량한 생존을 보였으며 역시 비종양 조직에서 통계적인 의미가 있었다(p<0.01). 결론: 제1기 비소세포폐암 환자의 절제 폐엽 조직 중 비종양 조직에서의 MMP-2 활성도는 재발 및 생존과 연관성이 있으며 예후 인자로서의 가능성이 있다.

Performance evaluation method for read mapping tool in clinical panel sequencing

이호준,이기욱,이태섭,박동현,정종석,이청,박웅양,손대순 한국유전학회 2018 Genes & Genomics Vol.40 No.2

In addition to the rapid advancement in Next- Generation Sequencing (NGS) technology, clinical panel sequencing is being used increasingly in clinical studies and tests. However, tools that are used in NGS data analysis have not been comparatively evaluated in performance for panel sequencing. This study aimed to evaluate the tools used in the alignment process, the first procedure in bioinformatics analysis, by comparing tools that have been widely used with ones that have been introduced recently. With the accumulated panel sequencing data, detected variant lists were cataloged and inserted into simulated reads produced from the reference genome (h19). The amount of unmapped reads and misaligned reads, mapping quality distribution, and runtime were measured as standards for comparison. As the most widely used tools, Bowtie2 and BWA–MEM each showed explicit performance with AUC of 0.9984 and 0.9970 respectively. Kart, maintaining superior runtime and less number of misaligned read, also similarly possessed high level of AUC (0.9723). Such selection and optimization method of tools appropriate for panel sequencing can be utilized for fields requiring error minimization, such as clinical application and liquid biopsy studies.

간전이를 동반한 대장암 환자에서 원발 종양 및 간전이 종양의 베타-카테닌 발현

한상아,박치민,강신재,송상용,김상희,손대순,윤성현,이우용,전호경 대한대장항문학회 2004 Annals of Coloproctolgy Vol.20 No.6

Benchmark Database for Process Optimization and Quality Control of Clinical Cancer Panel Sequencing

성동형,정종석,이기욱,김숙영,김병석,송정근,정성원,이태섭,박동현,이병기,박웅양,손대순 한국생물공학회 2019 Biotechnology and Bioprocess Engineering Vol.24 No.5

With advances in Next Generation Sequencing (NGS) technology, individual institutes and research consortia have publicly released large-scale accumulated genomic data obtained in various projects. NGS technology has also been rapidly adopted in clinical practice, and many governments and research organizations have established a regulatory framework and guidelines to ensure the accuracy and reliability of NGS-based testing. These guidelines are essential for the safe use of NGS-based testing, but do not provide enough details that can be specifically applied to the various applications of NGS. In the clinical setting of NGS technology, clinical laboratories should optimize the NGS workflow for their specific uses and performance should be thoroughly evaluated through numerous experiments. However, process optimization and performance evaluation are a great burden to the laboratory in terms of cost and time because of the technical characteristics of NGS technology. The Samsung Medical Center (SMC) has developed and utilized cancer panel sequencing, namely CancerSCAN, which is approved for clinical use by the Ministry of Food and Drug Safety (MFDS) in Korea. SMC has performed various experiments to optimize and evaluate the process of CancerSCAN. In this study, we developed a benchmark database for integrating and sharing these data for process optimization of cancer panel sequencing. This benchmark database contains information on data production and provides functionalities for searching, browsing, and downloading experimental data and raw data files. This benchmark database will be beneficial to researchers, laboratory staff, or potential stakeholders. Database URL: http://129.150.178.10:8080/qms/nqbp/nqbp_home.do

Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer

Hye Hyeon Eum,권민석,Ryu Daeun,Jo Areum,Chung Woosung,Kim Nayoung,홍유래,손대순,Kim Seung Tae,Lee Jeeyun,이혜옥,박웅양 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Gastric cancer (GC) patients develop malignant ascites as the disease progresses owing to peritoneal metastasis. GC patients with malignant ascites have a rapidly deteriorating clinical course with short survival following the onset of malignant ascites. Better optimized treatment strategies for this subset of patients are needed. To define the cellular characteristics of malignant ascites of GC, we used single-cell RNA sequencing to characterize tumor cells and tumor-associated macrophages (TAMs) from four samples of malignant ascites and one sample of cerebrospinal fluid. Reference transcriptomes for M1 and M2 macrophages were generated by in vitro differentiation of healthy blood-derived monocytes and applied to assess the inflammatory properties of TAMs. We analyzed 180 cells, including tumor cells, macrophages, and mesothelial cells. Dynamic exchange of tumor-promoting signals, including the CCL3–CCR1 or IL1B–IL1R2 interactions, suggests macrophage recruitment and anti-inflammatory tuning by tumor cells. By comparing these data with reference transcriptomes for M1-type and M2-type macrophages, we found noninflammatory characteristics in macrophages recovered from the malignant ascites of GC. Using public datasets, we demonstrated that the single-cell transcriptome-driven M2-specific signature was associated with poor prognosis in GC. Our data indicate that the anti-inflammatory characteristics of TAMs are controlled by tumor cells and present implications for treatment strategies for GC patients in which combination treatment targeting cancer cells and macrophages may have a reciprocal synergistic effect.

Clinical Targeted Next-Generation Sequencing Panels for Detection of Somatic Variants in Gliomas

신혜미,Jason K. Sa,배준설,구하림,진선휘,조희진,최승원,경종민,김자연,서윤지,정제균,Nayoung K.D. Kim,손대순,정종석,이태섭,공두식,최정원,설호준,이정일,서연림,박웅양,남도현 대한암학회 2020 Cancer Research and Treatment Vol.52 No.1

Purpose Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.