조기 유방암 환자를 위한 다지표 예후 예측 검사 GenesWellTM BCT의 분석적 성능 시험
An Analytical Validation of the GenesWellTM BCT Multigene Prognostic Test in Patients with Early Breast Cancer
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GenesWellTM BCT는 호르몬 수용체 양성, HER2 음성, 및pN0 또는 1인 조기 유방암 환자의 10년내 타 장기 전이 재발 위험도를 제시하는 다지표 예후 예측 검사로, 예후에 대한 위험을BCT Score로 제시한다. 본 연구에서는 GenesWellTM BCT의분석적 성능을 검사하였다. 조기 유방암 환자의 FFPE 검체로 부터 추출한 RNA를 대상으로 GenesWellTM BCT 수행하여, 12개유전자의 발현값을 측정하였다. GenesWellTM 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. GenesWellTM BCT는 1 ng/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 영향을미치지 않음을 확인할 수 있었다. 이들 결과는 GenesWellTM BCT가 95% 이상의 항상성을 나타내는 높은 분석적 성능을 가지고 있음을 제시한다.
Abstract
GenesWellTM BCT is a 12-gene test suggesting the prognostic risk score (BCT Score) for distant metastasis within the first 10 years in early breast cancer patients with hormone receptor-positive, HER2-negative, and pN0∼1 tumors. In this study, we validated the analytical performance of GenesWellTM BCT. Gene expression values were measured by a one-step, real-time qPCR, using RNA extracted from FFPE specimens of early breast cancer patients. Limit of Blank, Limit of Detection, and dynamic range for each of the 12 genes were assessed by serially diluted RNA pools. The analytical precision and specificity were evaluated by three different RNA samples representing low risk group, high risk group, and near-cutoff group in accordance with their BCT Scores. GenesWellTM BCT could detect gene expression of each of the 12 genes from less than 1 ng/L of RNA. Repeatability and reproducibility across multiple testing sites resulted in 100% and 98.3% consistencies of risk classification, respectively. Moreover, it was confirmed that the potential interference substances does not affect the risk classification of the test. The findings demonstrate that GenesWellTM BCT have high analytical performance with over 95% consistency for risk classification.
참고문헌 (21)
- "GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012" (2012)[URL]
- World Cancer Report 2014, "International Agency for Research on Cancer", International Agency for Research on Cancer, ~ (2014)
- 김지선, "The Basic Facts of Korean Breast Cancer in 2011: Results of a Nationwide Survey and Breast Cancer Registry Database", Journal of Breast Cancer, 17(2), pp.99~106 (2014), 한국유방암학회
- Sinn P, "Multigene assays for classification, prognosis, and prediction in breast cancer: A critical review on the background and clinical utility", Geburtshilfe Frauenheilkd, 73(9), pp.932~940 (2013)
- Rouzier R, "Multigene assays and molecular markers in breast cancer:systematic review of health economic analyses", Breast Breast Cancer Res Treat, 139, pp.621~637 (2013)
- Gyorffy B, "Multigene prognostic tests in breast cancer: past, present, future", Breast Cancer Res, 17, pp.11~ (2015)
- "NCCN Clinical practice guidelines in oncology: Breast cancer" (2017)[URL]
- Harris L, "Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer", J Clin Oncol, 25, pp.5287~5312 (2007)
- Gong GY, "A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+", HER2- early breast cancer, 2017, ~
- Bustin SA, "The MIQE Guidelines: minimum information for publication of quantitative real-time PCR experiments", Clin Chem, 55(4), pp.611~622 (2009)
- David AA, "Limit of blank, limit of detection and limit of quantitation", Clin Biochem Rev, 29(Suppl 1), pp.49~52 (2008)
- Clinical and Laboratory Standards Institute, "Evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline. CLSI document EP06-A", Clinical and Laboratory Standards Institute, ~ (2003)
- Clinical and Laboratory Standards Institute, "Evaluation of detection capability for clinical laboratory measurement procedures;approved guideline – second edition. CLSI document EP17-A2", Clinical and Laboratory Standards Institute, ~ (2012)
- Clinical and Laboratory Standards Institute, "Evaluation of precision of quantitative measurement procedures; approved guideline - third edition. CLSI document EP05-A3", Clinical and Laboratory Standards Institute, ~ (2014)
- Clinical and Laboratory Standards Institute, "Interference testing in clinical chemistry; approved guideline – second edition. CLSI document EP07-A2", Clinical and Laboratory Standards Institute, ~ (2005)
- Fisher B, "Treatment of lymph-node-negative, oestrogen-receptorpositive breast cancer: Long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials", Lancet, 364(9437), pp.858~868 (2004)
- Early Breast Cancer Trialists' Collaborative Group, "Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials", Lancet, 365(9472), pp.1687~1717 (2005)
- Huober J, "Adjuvant! When the new world meets the old world", Lancet Oncology, 10(11), pp.1028~1029 (2009)
- "Center for Devices and Radiological Health: Guidance for industry and FDA staff - class II special controls guidance document: Gene expression profiling test system for breast cancer prognosis" (2007)[URL]
- Kronenwett R, "Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test", BMC Cancer, 12, pp.456~ (2012)
- Cronin M, "Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer", Clin Chem, 53(6), pp.1084~1091 (2007)