Background/Objectives: Colorectal cancer (CRC) is the third most commonly occurring cancer. Apoptosis is a fundamental cellular process of programmed cell death, and although many pathways for inducing apoptosis may exist, only the intrinsic and the extrinsic pathways have been demonstrated in detail. This study investigated the expression of BAD, BID, BCL2, MDM2, p53, Ki-67, and PUMA in primary CRC, paired lymph node metastases, and adjacent normal mucosa and explored their associations with clinicopathologic features and patient outcomes.Methods: One hundred thirty patients who underwent surgery for resectable CRC were included in the study. FFPE tumor tissue samples were prospectively collected and used for the construction of the TMA blocks from the primary tumor, paired lymph node metastasis, and paired normal mucosa. Immunohistochemistry for BAD, BID, BCL2, MDM2, p53, Ki-67, and PUMA antibodies was performed.Results: Univariate analysis showed reduced cancer-specific (CSS), disease-free (DFS), and overall survival (OS) in patients with lymphatic invasion, ≥4 positive lymph nodes, poorly differentiated tumors, older age (≥65), right-sided tumors, stage IIIC disease, or no chemotherapy. Multivariate analysis identified lymphovascular invasion, ≥4 metastatic nodes, and high Ki-67 as independent predictors of worse DFS and CSS, with low BAD expression additionally predicting DFS. For OS, adverse predictors included nodal burden, tumor location, absence of chemotherapy, and high p53, MDM2, and Ki-67 expression. Notably, combined high PUMA and low p53 expression independently predicted poorer CSS and OS.Conclusions: High expression of PUMA combined with low expression of p53 and a high expression of Ki-67 were independent unfavorable prognostic indicators for both OS and CSS. Further studies are required to clarify the prognostic and therapeutic role of these markers in CRC.
背景/目的：结直肠癌是全球第三大常见恶性肿瘤。细胞凋亡是程序性细胞死亡的基本过程，虽然可能存在多种诱导凋亡的途径，但目前仅内源性途径和外源性途径得到详细阐明。本研究检测了BAD、BID、BCL2、MDM2、p53、Ki-67及PUMA在原发性结直肠癌组织、配对淋巴结转移灶及癌旁正常黏膜中的表达情况，并探讨其与临床病理特征及患者预后的相关性。 方法：本研究纳入130例接受根治性手术的结直肠癌患者。前瞻性收集福尔马林固定石蜡包埋肿瘤组织样本，构建包含原发灶、配对淋巴结转移灶及配对正常黏膜的组织芯片。采用免疫组织化学法检测BAD、BID、BCL2、MDM2、p53、Ki-67及PUMA蛋白表达。 结果：单因素分析显示，存在淋巴管侵犯、≥4枚淋巴结转移、低分化肿瘤、高龄（≥65岁）、右半结肠肿瘤、IIIC期疾病或未接受化疗的患者，其癌症特异性生存期、无病生存期和总生存期均显著缩短。多因素分析表明，淋巴血管侵犯、≥4枚转移淋巴结及高Ki-67表达是预测较差无病生存期和癌症特异性生存期的独立危险因素，而低BAD表达可额外预测无病生存期。对于总生存期，不良预测因素包括淋巴结转移负荷、肿瘤位置、未接受化疗以及高p53、MDM2和Ki-67表达。值得注意的是，高PUMA联合低p53表达可独立预测较差的癌症特异性生存期和总生存期。 结论：高PUMA联合低p53表达以及高Ki-67表达是预测结直肠癌患者总生存期和癌症特异性生存期的独立不良预后指标。未来需进一步研究明确这些标志物在结直肠癌中的预后价值及治疗指导意义。
肿瘤(癌症)患者之家