嘌呤/嘧啶内切核酸酶 1 在结直肠癌中的表达及其与肿瘤进展和预后的关系。
Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.
机构信息
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
出版信息
In Vivo. 2023 Sep-Oct;37(5):2070-2077. doi: 10.21873/invivo.13304.
BACKGROUND/AIM: Over-expression of apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated to be associated with cancer progression, chemo- and radioresistance in various cancers. This study examined the expression of APE1 and its relation to tumor progression and prognosis in patients with colorectal cancer (CRC).
MATERIALS AND METHODS
We investigated 193 patients with CRC who received curative surgery for whom formalin-fixed and paraffin-embedded blocks were available, and long-term tumor-specific survival rate analysis was possible. The expression of APE1 was investigated by reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry in CRC and lymph node tissues. The apoptosis, proliferation, and angiogenesis of CRC cells were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34 antibodies.
RESULTS
APE1 was over-expressed in CRC and metastatic lymph node tissues compared with normal colorectal mucosa and non-metastatic lymph node tissues. Over-expression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival. Multivariate analysis demonstrated that APE1, perineural invasion, and lymph node metastasis were the independent prognostic factors associated with overall survival. The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors. However, there was no significant association between APE1 expression and the apoptotic index or microvessel density.
CONCLUSION
Over-expression of APE1 is significantly associated with tumor progression and poor survival in patients with CRC. Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.
背景/目的：研究表明，脱嘌呤/脱嘧啶核酸内切酶 1（APE1）的过表达与多种癌症的肿瘤进展、化疗和放疗耐药有关。本研究探讨了 APE1 在结直肠癌（CRC）患者中的表达及其与肿瘤进展和预后的关系。
材料和方法
我们研究了 193 例接受根治性手术治疗且有福尔马林固定和石蜡包埋组织块的 CRC 患者，并且可以进行长期肿瘤特异性生存分析。通过逆转录-聚合酶链反应、western blot 和免疫组织化学法检测 CRC 和淋巴结组织中 APE1 的表达。使用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法和 Ki-67 和 CD34 抗体的免疫组织化学染色法检测 CRC 细胞的凋亡、增殖和血管生成。
结果
与正常结直肠黏膜和非转移性淋巴结组织相比，CRC 和转移性淋巴结组织中 APE1 过表达。APE1 的过表达与晚期、血管淋巴管侵犯、神经周围侵犯、更深的肿瘤侵袭、淋巴结转移、远处转移和不良生存显著相关。多变量分析表明，APE1、神经周围侵犯和淋巴结转移是与总生存期相关的独立预后因素。APE1 阳性肿瘤的平均 Ki-67 标记指数值明显高于 APE1 阴性肿瘤。然而，APE1 表达与凋亡指数或微血管密度之间没有显著关联。
结论
APE1 的过表达与 CRC 患者的肿瘤进展和不良生存显著相关。因此，APE1 可能是一种新的生物标志物，并为 CRC 提供了一个潜在的预后因素。
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