FEATURES OF COL1A1 EXPRESSION IN BREAST CANCER TISSUE OF YOUNG PATIENTS.

V Chekhun, O Mushii, T Zadvornyi, T Borikun, О Martyniuk, E Kashuba, A Kryzhanivska, A Andriiv, I Diakiv, N Lukianova
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Abstract

Background: In the last decades, the incidence of breast cancer (BCa) in young women has been increasing steadily. The quantitative indicators of expression of collagen, which play important role in stromal microenvironment, and their association with the age and survival rates of BCa patients have not been yet definitively clarified.

Aim: To investigate the relationship between the COL1A1 gene expression at the mRNA and protein levels in BCa tissue and the clinicopatological features and survival rates of BCa patients of different age groups.

Materials and methods: The study was conducted on the clinical material of 50 patients with stage I-III BCa. COL1A1 gene expression at the mRNA and protein levels in BCa tissue were studied using the real-time PCR and immunohistochemical methods, as well as the bioinformatic analysis (UALCAN and Kaplan - Meier Plotter databases).

Results: The bioinformatic analysis showed that BCa tissue is characterized by 6.0 times (p < 0.05) higher level of COL1A1 mRNA compared to normal breast tissue. The correlation of COL1A1 expression at the mRNA and protein levels with the molecular subtype of neoplasms was demonstrated. According to Kaplan - Meier Plotter database, a low level of expression of COL1A1 protein level in BCa tissue is associated with lower rates of relapse-free survival of patients. The ex vivo study of the clinical material revealed a decrease in COL1A1 protein expression in tumor tissue of young patients with BCa of T3 category (p < 0.0374), low differentiation grade (p < 0.0163) and basal molecular subtype (p < 0.0001). A correlation between the expression of COL1A1 at the mRNA and protein levels and the expression status of estrogen receptors (p < 0.0001) and progesterone receptors (p < 0.0040) was established. The relapse-free 3-year survival rate of young BCa patients is significantly lower in the presence of a low COL1A1 optical density index in the tumor tissue.

Conclusions: The identified relationship between COL1A1 expression and such indicators of BCa malignancy as tumor size, differentiation grade, molecular subtype, receptor status, and the recurrencefree survival of patients indicates the prospects of its use to predict the aggressiveness of the BCa course in young patients.

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年轻患者乳腺癌组织中 col1a1 的表达特征。
背景:近几十年来,年轻女性乳腺癌(BCa)的发病率持续上升。目的:研究 BCa 组织中 COL1A1 基因 mRNA 和蛋白水平的表达与不同年龄组 BCa 患者临床病理特征和生存率之间的关系:研究对象为50例I-III期BCa患者的临床资料。采用实时 PCR 和免疫组化方法研究了 BCa 组织中 COL1A1 基因 mRNA 和蛋白水平的表达情况,并进行了生物信息学分析(UALCAN 和 Kaplan - Meier Plotter 数据库):生物信息学分析表明,与正常乳腺组织相比,BCa 组织的 COL1A1 mRNA 水平高出 6.0 倍(P < 0.05)。COL1A1在mRNA和蛋白质水平的表达与肿瘤的分子亚型相关。根据 Kaplan - Meier Plotter 数据库,BCa 组织中 COL1A1 蛋白水平的低表达与患者较低的无复发生存率有关。对临床材料进行的体外研究显示,在T3类(p < 0.0374)、低分化等级(p < 0.0163)和基底分子亚型(p < 0.0001)的年轻BCa患者的肿瘤组织中,COL1A1蛋白表达量有所下降。COL1A1在mRNA和蛋白水平的表达与雌激素受体(p < 0.0001)和孕激素受体(p < 0.0040)的表达状态之间存在相关性。如果肿瘤组织中的COL1A1光密度指数较低,年轻BCa患者的3年无复发生存率就会明显降低:结论:COL1A1表达与肿瘤大小、分化等级、分子亚型、受体状态等BCa恶性程度指标以及患者无复发生存率之间的关系已被确定,这表明COL1A1有望用于预测年轻患者BCa病程的侵袭性。
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