Zhang Li, Liu Yu, Ding Ying, Deng Yinqian, Chen Huanyu, Hu Fan, Fan Jun, Lan Xiaoli, Cao Wei
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Molecular Imaging, Wuhan, China.
Front Oncol. 2023 Apr 27;13:1065744. doi: 10.3389/fonc.2023.1065744. eCollection 2023.
PURPOSE/BACKGROUND: Microsatellite instability (MSI) status is a significant biomarker for the response to immune checkpoint inhibitors, response to 5-fluorouracil-based adjuvant chemotherapy, and prognosis in colorectal carcinoma (CRC). This study investigated the predictive value of intratumoral-metabolic heterogeneity (IMH) and conventional metabolic parameters derived from F-FDG PET/CT for MSI in patients with stage I-III CRC.
This study was a retrospective analysis of 152 CRC patients with pathologically proven MSI who underwent F-FDG PET/CT examination from January 2016 to May 2022. Intratumoral-metabolic heterogeneity (including heterogeneity index [HI] and heterogeneity factor [HF]) and conventional metabolic parameters (standardized uptake value [SUV], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) of the primary lesions were determined. MTV and SUV were calculated on the basis of the percentage threshold of SUVs at 30%-70%. TLG, HI, and HF were obtained on the basis of the above corresponding thresholds. MSI was determined by immunohistochemical evaluation. Differences in clinicopathologic and various metabolic parameters between MSI-High (MSI-H) and microsatellite stability (MSS) groups were assessed. Potential risk factors for MSI were assessed by logistic regression analyses and used for construction of the mathematical model. Area under the curve (AUC) were used to evaluate the predictive ability of factors for MSI.
This study included 88 patients with CRC in stages I-III, including 19 (21.6%) patients with MSI-H and 69 (78.4%) patients with MSS. Poor differentiation, mucinous component, and various metabolic parameters including MTV, MTV, MTV, and MTV, as well as HI, HI, HI, and HF in the MSI-H group were significantly higher than those in the MSS group (all < 0.05). In multivariate logistic regression analyses, post-standardized HI by Z-score ( = 0.037, OR: 2.107) and mucinous component ( < 0.001, OR:11.394) were independently correlated with MSI. AUC of HI and our model of the HI + mucinous component was 0.685 and 0.850, respectively ( = 0.019), and the AUC of HI in predicting the mucinous component was 0.663.
Intratumoral-metabolic heterogeneity derived from F-FDG PET/CT was higher in MSI-H CRC and predicted MSI in stage I-III CRC patients preoperatively. HI and mucinous component were independent risk factors for MSI. These findings provide new methods to predict the MSI and mucinous component for patients with CRC.
目的/背景：微卫星不稳定性（MSI）状态是结直肠癌（CRC）中免疫检查点抑制剂反应、基于5-氟尿嘧啶的辅助化疗反应及预后的重要生物标志物。本研究探讨了瘤内代谢异质性（IMH）及源自F-FDG PET/CT的传统代谢参数对I-III期CRC患者MSI的预测价值。
本研究对2016年1月至2022年5月期间接受F-FDG PET/CT检查且病理证实为MSI的152例CRC患者进行回顾性分析。测定原发灶的瘤内代谢异质性（包括异质性指数[HI]和异质性因子[HF]）及传统代谢参数（标准化摄取值[SUV]、代谢肿瘤体积[MTV]和总病灶糖酵解[TLG]）。MTV和SUV基于SUV在30%-70%时的百分比阈值进行计算。TLG、HI和HF基于上述相应阈值获得。MSI通过免疫组化评估确定。评估MSI-High（MSI-H）组和微卫星稳定（MSS）组之间临床病理及各种代谢参数的差异。通过逻辑回归分析评估MSI的潜在危险因素，并用于构建数学模型。曲线下面积（AUC）用于评估MSI相关因素的预测能力。
本研究纳入88例I-III期CRC患者，其中19例（21.6%）为MSI-H，69例（78.4%）为MSS。MSI-H组中，低分化、黏液成分以及包括MTV、MTV、MTV和MTV等各种代谢参数，以及HI、HI、HI和HF均显著高于MSS组（均P<0.05）。在多因素逻辑回归分析中，经Z评分标准化后的HI（P = 0.037，OR：2.107）和黏液成分（P<0.001，OR：11.394）与MSI独立相关。HI及HI+黏液成分模型的AUC分别为0.685和0.850（P = 0.019），HI预测黏液成分的AUC为0.663。
源自F-FDG PET/CT的瘤内代谢异质性在MSI-H CRC中更高，并可在术前预测I-III期CRC患者的MSI。HI和黏液成分是MSI的独立危险因素。这些发现为CRC患者预测MSI和黏液成分提供了新方法。
