ABSTRACT

Cancer diagnosis and therapy is quickly moving from the traditional histology-based approaches to genomic stratification, providing a huge opportunity for radiogenomics, associating imaging features with genomic data. Genome sequencing is time consuming, expensive and invasive whereas ¹⁸F-FDG PET/CT is readily available, fast and noninvasive. The aim of this study was to determine the relationship between the maximum standardized uptake value (SUV_max) and the frequency of 11 common oncogenic anomalies determined by specific common genomic alterations in tissue biopsies from patients with cancer. We retrospectively studied 102 consecutive untreated patients with gastrointestinal, lung, and breast cancer who underwent ¹⁸F-FDG PET/CT imaging, shortly prior to molecular testing by a biopsy for genomic profiling that consisted of 11 common DNA alterations: (1) TP53, (2) DNA repair, (3) EGFR, (4) PI3K/AKT/MTOR (PAM) pathway including PTEN, PIK3CA, AKT, TSC, CCNB1, MTOR, FBXW2, and NF2, (5) MEK, (6) CYCLIN including CCND,CDK, CDKN, and RB, (7) WNT, (8) ALK, (9) MYC, (10) MET, and (11) FGF/FGFR. Higher SUV_max was associated with the presence of TP53 and PAM genomic anomalies (p < .05), but not the other 9 gene groups (p > .05). More importantly, SUV_max was positively correlated with total number of oncogenic anomalies (r = 0.27, p = .005). We propose higher SUV_max as an indicator for total number of common oncogenic anomalies. This finding is a step forward in noninvasive stratification of cancer patients, in terms of the overall load of oncogenic anomalies, based on their SUV_max.

摘要

癌症诊断和治疗正迅速从传统的基于组织学的方法转向基因组分层，为放射基因组学提供了巨大的机会，将成像特征与基因组数据相关联。基因组测序耗时、昂贵且有创，而¹⁸ F-FDG PET/CT 容易获得、快速且无创。本研究的目的是确定最大标准化摄取值 (SUV _max ) 与 11 种常见致癌异常的频率之间的关系，这些异常由癌症患者组织活检中的特定常见基因组改变确定。我们回顾性研究了 102 名连续未经治疗的胃肠道癌、肺癌和乳腺癌患者，他们接受了¹⁸F-FDG PET/CT 成像，在通过活检进行基因组分析的分子检测之前不久，包括 11 种常见的 DNA 改变：(1) TP53，(2) DNA 修复，(3) EGFR，(4) PI3K/AKT/ MTOR (PAM) 通路，包括 PTEN、PIK3CA、AKT、TSC、CCNB1、MTOR、FBXW2 和 NF2，(5) MEK，(6) CYCLIN，包括 CCND、CDK、CDKN 和 RB，(7) WNT，(8) ALK、(9) MYC、(10) MET 和 (11) FGF/FGFR。较高的 SUV _max与 TP53 和 PAM 基因组异常的存在相关 ( p < .05)，但与其他 9 个基因组无关 ( p > .05)。更重要的是，SUV _max与致癌异常的总数呈正相关（r = 0.27，p = .005）。我们建议更高的 SUV _max作为常见致癌异常总数的指标。根据癌症患者的 SUV _max，就致癌异常的总体负荷而言，这一发现是在对癌症患者进行无创分层方面向前迈进了一步。