Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Pathol Oncol Res. 2021 Apr 9;27:594724. doi: 10.3389/pore.2021.594724. eCollection 2021.
The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues ( < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern ( < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant ( > 0.05), whereas Beclin-1 expression was significantly associated with OS ( < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.
自噬和细胞凋亡在食管鳞状细胞癌（ESCC）的预后评估和治疗中的作用仍有待阐明。在这里，我们对 ESCC 的组织病理学进行了回顾性研究，研究了食管癌细胞组织中 Beclin-1 和 Bcl-2 蛋白（两者均与自噬和细胞凋亡相关）的表达，并分析了这些蛋白对 ESCC 预后的意义。在本研究中，ESCC 中 Beclin-1 的表达水平明显低于相邻组织（<0.01），而 Bcl-2 的表达水平则相反（<0.01）。此外，Beclin-1 表达水平低与 ESCC 分期较晚和淋巴结转移有关。然而，Bcl-2 表达水平高与 ESCC 分期较晚、肿瘤侵袭较深和淋巴结转移有关。此外，Bcl-2 表达与 OS 之间的关系不显著（>0.05），而 Beclin-1 表达与 OS 显著相关（<0.05）。亚组分析表明，在高 Bcl-2 表达组中，Beclin-1 表达与 OS 显著相关，但在低 Bcl-2 表达组中则不相关。重要的是，Beclin-1 的上调或下调分别与 Bcl-2 高表达而非低表达时的 EC9706 细胞侵袭显著相关。这些发现表明，自噬和细胞凋亡状态及其活性的差异可能促进恶性肿瘤分化，导致更具侵袭性的食管鳞状细胞表型和更差的生存预后。在这里，Beclin-1 被证明是高 Bcl-2 表达人群中 ESCC 患者有前途的预后生物标志物和治疗靶点。
