Ionescu Adriana, Bilteanu Liviu, Geicu Ovidiu Ionut, Iordache Florin, Stanca Loredana, Pisoschi Aurelia Magdalena, Miron Adrian, Serban Andreea Iren, Calu Valentin
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Blvd., Splaiul Independentei, 050095 Bucharest, Romania.
Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 105 Blvd., Splaiul Independentei, 050097 Bucharest, Romania.
Cancers (Basel). 2022 Jun 4;14(11):2792. doi: 10.3390/cancers14112792.
Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its predicted evolution.
Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF, and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. We evaluated correlations between mutations of AFs and also between the mutations and histopathology features (tumor staging, inflammation, differentiation, and invasiveness).
KRAS G12/G13 mutations were present in all patients. KRAS Q61 was significantly associated with poor differentiation, high desmoplastic reaction, invasiveness (ypT4), and metastasis (ypM1). NRAS and BRAF were associated with the right-side localization of tumors. Diabetic patients had a higher risk to exhibit NRAS G12/G13 mutations. BRAF and NRAS G12/G13 mutations co-existed in tumors with invasiveness limited to the submucosa.
The associations we found and the mutational AF we reported may help to understand disease processes and may be considered as potential CCR biomarker candidates. In addition, we propose representative mutation panels associated with specific clinical and histopathological features of CRC, as a unique opportunity to refine the degree of personalization of CRC treatment.
生物标志物谱应能连贯地描述结直肠癌（CRC）分期及其预测的进展情况。
我们使用液滴数字PCR检测了60个肿瘤中KRAS、NRAS、BRAF和EGFR突变的等位基因频率（AF）。我们采用成对关联方法来估计涉及AF突变的风险，将其作为临床数据的结果变量以及肿瘤分期的预测变量。我们评估了AF突变之间以及这些突变与组织病理学特征（肿瘤分期、炎症、分化和侵袭性）之间的相关性。
所有患者均存在KRAS G12/G13突变。KRAS Q61与低分化、高促纤维增生反应、侵袭性（ypT4）和转移（ypM1）显著相关。NRAS和BRAF与肿瘤的右侧定位有关。糖尿病患者出现NRAS G12/G13突变的风险更高。BRAF和NRAS G12/G13突变共存于侵袭仅限于黏膜下层的肿瘤中。
我们发现的关联以及报道的突变AF可能有助于理解疾病进程，并且可被视为潜在的结直肠癌生物标志物候选物。此外，我们提出了与CRC特定临床和组织病理学特征相关的代表性突变组，作为提高CRC治疗个性化程度的独特机会。
