PO.PR01.01 · 预防研究
评估ABCC1作为喉癌健康结局潜在预后生物标志物的价值
Evaluating ABCC1 as a potential prognostic biomarker in laryngeal cancer health outcomes
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：ABCC1过表达与多种癌症的总生存不良相关，并与化疗反应下降相关。我们的体内和体外研究显示，非洲血统个体的喉鳞状细胞癌（LSCC）中ABCC1表达更高。本研究进一步探讨ABCC1作为喉癌健康结局潜在预后和预测标志物的价值。
方法：通过RT-PCR对来自不同人群的32例晚期LSCC患者肿瘤组织的ABCC1基因表达进行评估。对来自不同血统晚期LSCC患者的61份石蜡包埋组织构建组织微阵列（TMA），并进行ABCC1蛋白表达的免疫组化（IHC）。使用基于机器学习的数字病理软件（QuPath）将ABCC1 IHC蛋白表达半定量为H评分。通过多变量Cox比例风险（CPH）模型评估年龄、治疗、自我报告的血统、N分期、肿瘤组织学分级和ABCC1 H评分作为患者死亡风险预测因素的价值。采用Cox风险评分中位数（截断值>0.971）将患者分层为低死亡风险组和高死亡风险组。通过卡方分析探讨低死亡风险组和高死亡风险组中临床特征与ABCC1之间的关系。采用Kaplan-Meier法评估总生存。
结果：与参照人群相比，非洲血统患者的LSCC显示ABCC1基因表达升高2.2倍且ABCC1蛋白表达（H评分）更高（p<0.05）。在控制治疗因素后，ABCC1 H评分较低的非洲血统患者具有高死亡风险（p<0.05），而参照人群中患有转移性疾病且ABCC1 H评分较高的患者具有低死亡风险（p<0.05）。总体而言，高风险患者的总生存显著更差（HR=2.46，95% CI [1.27-4.74]，log rank p<0.01），高死亡风险与低ABCC1 H评分及区域转移性疾病相关（p<0.05）。
结论：尽管非洲血统的LSCC患者与参照人群相比具有更高的ABCC1表达，但在该人群中低ABCC1 H评分带来更高的死亡风险。参照人群中ABCC1 H评分较高的LSCC患者尽管患有区域转移性疾病，死亡风险仍较低。未来研究将探讨ABCC1表达对不同血统人群治疗结局的机制影响。
查看英文原文 English abstract
Background : Overexpression of ABCC1 is associated with poor overall survival across many cancers and has been associated with decrease response to chemotherapy. Our in vivo and in vitro studies have shown that ABCC1 expression is higher in laryngeal squamous cell carcinoma (LSCC) from individuals with African heritage. Here, we further investigate ABCC1 as a potential prognostic and predictive marker in laryngeal cancer health outcomes.
Methods: ABCC1 gene expression was assessed in tumor tissue from 32 advanced-stage LSCC patients from differing populations via RT-PCR. Immunohistochemistry (IHC) for ABCC1 protein expression was performed on tissue microarrays (TMAs) generated from 61 paraffin-embedded tissues of advanced stage LSCC from patients of differing heritages. Machine learning based digital pathology software (QuPath) was used to semi-quantitate ABCC1 IHC protein expression as H scores. Age, treatment, self-reported heritage, N stage, tumor histologic grade, and ABCC1 H-scores were evaluated as predictors of patient mortality risk via multivariable Cox proportional hazards (CPH) model. The median Cox risk score (cutoff > 0.971) was used to stratify patients into low and high mortality risk groups. The relationship among the clinical features and ABCC1 in low and high mortality risk groups was explored by Chi Square analysis. Overall survival was assessed using the Kaplan-Meier method.
Results : LSCCs from patients with African heritage demonstrated a 2.2-fold elevation in ABCC1 gene expression and higher ABCC1 protein expression (H-score) compared with the reference population (p < 0.05). Controlling for treatment, African heritage patients with low ABCC1 H-scores had a high mortality risk (p < 0.05), and patients from the reference population with metastatic disease and high ABCC1 H-scores had a low mortality risk (p < 0.05). Overall, high-risk patients had significantly worse overall survival (HR = 2.46, 95% CI [1.27-4.74], log rank p < 0.01) and high mortality risk was associated with low ABCC1 H-scores and regional metastatic disease (p < 0.05).
Conclusion : Although LSCC patients with African heritage have higher ABCC1 expression compared with the reference population, low ABCC1 H-scores carry a higher mortality risk in this group. LSCC patients from the reference population with high ABCC1 H-scores have reduced mortality risk despite having regional metastatic disease. Future studies will involve exploring mechanistic implications of ABCC1 expression on treatment outcomes across differing heritages.
利益披露 Disclosure
C. Gobin, None..
M. Chang, None..
J. Walker, None..
K. Fredenburg, None.