Abstract:
Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.
摘要:
乳腺癌(BC)是一种异质性疾病,其发展涉及多种途径。programming,和抗药性。自噬,负责自我消化受损细胞器的细胞过程,在癌症进展和化疗耐药方面被认为是杰出的参与者。Beclin1(BECN1)的单倍体功能不全,自噬蛋白,被认为有助于癌症的发病机制和进展。在我们的研究中,我们调查了一个BC女性埃及患者队列中BECN1的表达,以及通过评估其与2年随访后无病生存期(DFS)的相关性以及肿瘤临床病理特征的相关性来评估其预后作用。包括20个冷冻的雌性BC组织样品和17个邻近的正常组织,并检查BECN1的表达水平。尽管肿瘤组织显示出比其相应的正常组织1.02(0.04-19.59)低的表达0.73(0-8.95),没有统计学意义,p:0.463。BECN1表达与分期无关,淋巴结转移或肿瘤大小,p:分别为0.435、0.541、0.296。然而,在研究病例中,分级与BECN1mRNA表达之间存在统计学上显著的负相关,p:0.028。BECN1表达与DFS无统计学意义的相关性,P=0.944。然而,我们观察到三阴性(TNBC)病例的DFS率显着低于管腔BC患者,p:0.022,平均DFS19.0个月,而管腔BC患者的平均DFS为23.41个月。我们的研究强调了BECN1在BC发病机制中的潜在作用,显示BECN1表达与BC分化较差相关,表明其可能与疾病侵袭性有关。DFS两年随访显示TNBC亚型仍然与预后较差相关。