The KRAS, ATR and CHEK1 expression levels in endometrial cancer are the risk factors predicting recurrence

• Published in: PloS one 2024-04, Vol.19 (4), p.e0302075-e0302075
• Main Authors: Buchynska, Liubov, Gordiienko, Inna, Glushchenko, Nadiia, Iurchenko, Nataliia
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Adult; Aged; Analysis; Ataxia Telangiectasia Mutated Proteins - genetics; Ataxia Telangiectasia Mutated Proteins - metabolism; Biological markers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Checkpoint Kinase 1 - genetics; Checkpoint Kinase 1 - metabolism; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; Humans; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Prevention; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; ras Proteins - genetics; ras Proteins - metabolism; Relapse; Risk Factors; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0302075

Endometrial cancer is the most prevalent gynecologic malignancy with a high risk of recurrence. Local recurrence occurs in 7-20% of patients with treated stage I cancer within 3 years after primary treatment. In this study, we found significantly elevated mRNA expression levels of the oncoprotein KRAS, along with two replicative stress markers, ATR and CHEK1, in samples of endometrial carcinomas of endometrium (ECE) from patients with relapse. In contrast, mRNA expression levels of the studied genes were low and uniform in samples from patients without relapse. Elevated levels of KRAS protein and the phosphorylated form of ATR/CHEK1 were distinguishing features of recurrent ECE. A strong positive correlation was found between elevated mRNA and protein levels of the studied molecules. Elevated KRAS protein levels are characteristic of poorly differentiated (G3) endometrial carcinomas with deep myometrial invasion in patients without recurrence. In contrast, in patients with recurrence, higher protein levels of KRAS, pATR and pCHEK1 were observed in samples of G1-2 endometrial carcinomas, with statistically significant differences confirmed for pATR. High pCHEK1 protein levels are associated with deep tumor invasion in the myometrium among patients with recurrence. ROC analysis confirmed that evaluating the specificity and sensitivity of KRAS, pATR and pCHEK1 predicts recurrence development in patients with ECE. Our findings indicate that markers of replicative stress may play a significant role in ECE pathogenesis. Determining their levels in tumor samples after primary treatment could help define patients at high risk of recurrence and guide consequent courses of treatment.