简介：局部晚期直肠癌（LARC）的标准治疗是新辅助化疗联合放疗（nCRT）。为了选择最适合nCRT治疗的患者，需要预测性生物标志物。本研究的目的是评估临床、病理、放射学、与炎症相关的遗传学和血液学参数在预测nCRT后反应的作用。材料和方法：通过对已发表的转录组数据集进行体外分析，确定候选基因，然后使用定量实时聚合酶链式反应（qRT-PCR）测量其在术前的福尔马林固定石蜡嵌入（FFPE）样本中的表达水平。本研究于2020年6月至2022年1月间，对75例LARC患者进行了前瞻性纳入。在nCRT后的第8周，通过盆腔MRI和刚性直肠镜检查评估患者的肿瘤反应情况。对于出现临床完全缓解（cCR）且初始位置较远的肿瘤的患者，不建议立即进行手术治疗（“观察等待”方法）。手术后，使用Mandard的组织病理学肿瘤回归分级（TRG）对术后标本进行反应评估。临床完全缓解的患者和TRG 1和TRG 2术后类别的患者被定义为响应者（R），TRG 3-5的患者被定义为非响应者（NR）。结果：响应者组包括35例患者（46.6%），非响应者组占53.4%的患者。对已发表的转录组数据进行分析，确定了能够预测治疗反应的基因，并通过qRT-PCR在我们的队列中评估了其重要性。当比较手术患者（TRG1 vs. TRG4）的亚组时，IDO1的表达明显失调（p < 0.05）。在R和NR之间的血液学参数比较中，中性粒细胞-单核细胞比（NMR）、初始嗜碱性粒细胞、嗜酸性粒细胞和单核细胞计数的反应差异显著（p < 0.01）。根据MRI结果，非响应者更常见于外肌血管侵犯（p < 0.05）。结论：基于逻辑回归模型，与nCRT的良好反应相关的因素包括肿瘤形态学和血液学参数，这些参数可以从初始实验室结果（NMR、嗜酸性粒细胞、嗜碱性粒细胞和单核细胞计数）中轻松获得并进行常规分析，具有微创性。使用各种指标，初始嗜酸性粒细胞、嗜碱性粒细胞和单核细胞计数的综合分数表现出最佳的预测性能。版权所有©2023 Marinkovic、Stojanovic-Rundic、Stanojevic、Ostojic、Gavrilovic、Jankovic、Maksimovic、Stroggilos、Zoidakis、Castellví-Bel、Fijneman和Cavic。

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response. Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020-January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested ("watch and wait" approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05). Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.Copyright © 2023 Marinkovic, Stojanovic-Rundic, Stanojevic, Ostojic, Gavrilovic, Jankovic, Maksimovic, Stroggilos, Zoidakis, Castellví-Bel, Fijneman and Cavic.