GenesWell BCT

临床验证

GenesWell BCT 是已针对HR+, HER2-, pN0/1早期乳腺癌患者验证的预后诊断产品。

预后预测能力验证

为了验证 GenesWell BCT 的预后预测能力准确度, 我们在低风险人群和高风险人群之间比较了无远端转移生存率(DMFS), 无病生存率(DFS) 和总生存率(OS) 。

两组不同人群在各统计学指数上存在显著差异。通过GenesWell BCT 评估得出低风险人在无远端转移生存率、无病生存率、总生存都要高于高风险人群。

10年无远端转移生存率

10年无远端转移生存率

比较两组人群10年无远端转移生存率可以得出：低风险人群的10年无远端生存率比高风险人群要高出22.5%
10年无病生存率

10年无病生存率

比较两组人群10年无病生存率可以得出：低风险人群的10年无病生存率比高风险人群要高出30.1%
10年总生存率

10年总生存率

比较两组人群10年总生存率可以得出：低风险人群的10年总生存率比高风险人群要高出21.9%

A new molecular prognostic score for predicting the risk of distant metastasis in patients with HR+/HER2− early breast cancer: Gong, G. et al.
Scientific Reports | 2017

To make an optimal treatment decision for early stage breast cancer, it is important to identify risk of recurrence. Here, we developed and validated a new prognostic model for predicting the risk of distant metastasis in patients with pN0-N1, hormone receptor-positive, HER2-negative (HR+/HER2−) breast cancer treated with hormone therapy alone. RNA was extracted from formalin-fixed, paraffin-embedded tumor tissues and gene expression was measured by quantitative real-time reverse transcription-PCR. The relative expression of six novel prognostic genes was combined with two clinical variables (nodal status and tumor size) to calculate a risk score (BCT score). In the validation cohort treated with hormone therapy alone, the 10 year rate of distant metastasis in the high-risk group (26.3%) according to BCT score was significantly higher than that in the low-risk group (3.8%) (P < 0.001). Multivariate analysis adjusted for clinical variables revealed that BCT score is an independent predictor of distant metastasis. Moreover, the C-index estimate revealed that BCT score has a prognostic power superior to that of prognostic models based on clinicopathological parameters. The BCT score outperforms prognostic models based on traditional clinicopathological factors and predicts the risk of distant metastasis in patients with HR+/HER2− early breast cancer.

预测化疗受益

经验证，Geneswell 所区分的两组人群在进行化疗后，无远端转移生存率有所不同。

并不是所有人都能在联合化疗中获得受益。由于每个患者自身情况不同, 化疗得的受益可能截然相反。低风险组(BCT Score<4)的患者在仅接受内分泌疗法的条件下, 显示出 96.0%(92.5% ~ 99.7%) 的10年生存率。在接受化疗条件下, 10年生存率为96.4%(92.5% ~ 100%) 。两者相差仅为0.4%而且并无统计学显著差异(p-value=0.003, log-rank test).

低风险组(BCT Score<4)的患者在仅接受内分泌疗法的条件下, 显示出 65.4.0%(47.3% ~ 90.5%) 的10年生存率。在接受化疗条件下, 10年生存率为91.9%(84.5% ~ 99.9%) 。两者相差为26.5%且统计学差异显著(p-value=0.003, log-rank test).

BCT score predicts chemotherapy benefit in Asian patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer: Kwon. et al.
PloS one | 2018

The Breast Cancer Test (BCT) score has been validated for its ability to predict the risk of distant metastasis in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. This study aimed to examine the value of the BCT score for predicting the benefit of adjuvant chemotherapy for Korean women with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer. The study included 346 patients treated with either hormone therapy alone (n = 203) or hormone therapy plus chemotherapy (n = 143), and compared patient survival between the two treatment groups. The effect of BCT score on patient survival by treatment group was assessed using Cox proportional hazards models. Based on the results, the BCT score was prognostic for distant metastasis-free survival and breast cancer-specific survival in the hormone therapy alone group. There was no significant difference between the treatment groups in terms of 10-year distant metastasis-free survival in the overall patient population. However, when patients were classified as low risk (n = 266) and high risk (n = 80) according to the BCT score, addition of adjuvant chemotherapy to hormone therapy for patients classified as BCT high-risk group led to a significant improvement in 10-year distant metastasis-free survival, from 65.4% to 91.9% (hazard ratio, 0.18; 95% confidence interval, 0.05–0.64; P = 0.003); in contrast, there was no benefit for the BCT low-risk group. The stratification of patients according to the BCT score also identified clinically high-risk patients who may not benefit from chemotherapy. Results were similar for breast cancer-specific survival. In conclusion, the BCT score was not only of prognostic value but was also a predictor of chemotherapy benefit for Korean patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer.

9 项基因

通过对乳腺癌患者多项实验数据分析, GenesWell BCT 选择了和低风险/高风险人群有强相关性的9项基因。这些基因为 : 5 项增殖相关基因(UBE2C, TOP2A, RRM2, FOXM1, MKI67) 1项免疫相关基因 (BTN3A2) 和3项对照基因 (CTBP1, CUL1, UBQLN1).

预后基因

GenesWell BCT 体系中, 5项增殖相关的基因会促进癌细胞增殖, 这些基因如果高水平表达, 预后会变差。1项免疫相关基因可以抑制癌细胞增殖, 高水平表达时, 预后较好。

通过发现精准的预后相关基因可以更加准确判断远端转移或者复发风险

对照基因

基因可分为在大部分组织中表达的基因和只在特定器官和特定组织表达的基因。不随外部条件变化, 在大部分细胞中表达水平一致的基因可作为“对照基因”。

尤其对于通过比较来确定基因表达水平的检验来说, 对照基因的选择是必须而且极为重要的。

Geneswell BCT 通过多年的研究, 选择了可以在乳腺癌细胞中做准确对比分析的3项基因做为对照基因。

GenesWell BCT 研究
- 对照基因

Identification of Novel Reference Genes Using Multiplatform Expression Data and Their Validation for Quantitative Gene Expression Analysis: Kwon et al.
PLoS ONE | 2009

Normalization of mRNA levels using endogenous reference genes (ERGs) is critical for an accurate comparison of gene expression between different samples. Despite the popularity of traditional ERGs (tERGs) such as GAPDH and ACTB, their expression variability in different tissues or disease status has been reported. Here, we first selected candidate housekeeping genes (HKGs) using human gene expression data from different platforms including EST, SAGE, and microarray, and 13 novel ERGs (nERGs) (ARL8B, CTBP1, CUL1, DIMT1L, FBXW2, GPBP1, LUC7L2, OAZ1, PAPOLA, SPG21, TRIM27, UBQLN1, ZNF207) were further identified from these HKGs. The mean coefficient variation (CV) values of nERGs were significantly lower than those of tERGs and the expression level of most nERGs was relatively lower than high expressing tERGs in all dataset. The higher expression stability and lower expression levels of most nERGs were validated in 108 human samples including formalin-fixed paraffin-embedded (FFPE) tissues, frozen tissues and cell lines, through quantitative realtime RT-PCR (qRT-PCR). Furthermore, the optimal number of nERGs required for accurate normalization was as few as two, while four genes were required when using tERGs in FFPE tissues. Most nERGs identified in this study should be better reference genes than tERGs, based on their higher expression stability and fewer numbers needed for normalization when multiple ERGs are required.

GenesWell BCT 研究
- 预后基因

A prognostic model for lymph node-negative breast cancer patients based on the integration of proliferation and immunity: Oh et al.
Breast Cancer Res Treat | 2011

A model for a more precise prognosis of the risk of relapse is needed to avoid overtreatment of lymph node-negative breast cancer patients. A large derivation data set (n = 684) was generated by pooling three independent breast cancer expression microarray data sets. Two major prognostic factors, proliferation and immune response, were identified among genes showing significant differential expression levels between the good outcome and poor outcome groups. For each factor, four proliferation-related genes (p-genes) and four immunity-related genes (i-genes) were selected as prognostic marker in early breast cancer. The p-genes showed a predominantly negative correlation with survival time, while the i-genes showed a positive correlation, reflecting the beneficial effect of the immune response against deleterious proliferative activity.

GenesWell BCT 临床研究

Genecurix 以持续不断地进行临床研究建立 GenesWell BCT 的乳腺癌临床意义
到目前为止，和GenesWell BCT 相关的临床实验已对2,500多个临床样本进行了研究

TOTAL 2,584

已完成的 GenesWell BCT 临床实验 (Dec 2019)

진스웰 BCT

预后预测能力验证

10年无远端转移生存率

10年无病生存率

10年总生存率