i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
BMC Cancer. 2021 Apr 6;21(1):359. doi: 10.1186/s12885-021-08070-6.
Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC.
For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy.
In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy.
In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.
结直肠癌（CRC）仍然是全球范围内一个严重的健康问题。尽管在诊断和治疗方面取得了进展，但约有 15%至 30%的接受根治性肿瘤切除术的 II 期 CRC 患者会出现疾病复发。此外，这些患者手术后采用的治疗策略并不一致。这就迫切需要寻找新的 II 期 CRC 预后和预测生物标志物。
为此，我们使用了一家医院的 227 例 II 期 CRC 患者样本的系列研究，以评估 MUC2 粘蛋白和 CDX2 和 SOX2 转录因子免疫组化表达的生物标志物潜力。Kaplan-Meier 法生成无病生存曲线，然后使用对数秩检验进行比较，以确定具有不同蛋白表达、不同错配修复（MMR）状态和是否接受辅助化疗的病例的预后。
在这个 II 期 CRC 系列中，没有一种研究的生物标志物对患者的预后有预测价值。然而，在 CDX2 高表达的情况下，MUC2 低表达、SOX2 缺失或 MMR 功能正常的情况下，预示着预后明显更差。此外，MUC2 低表达的病例接受辅助化疗的获益明显更为显著。
总之，我们观察到 II 期 CRC 患者肿瘤中 MUC2 低表达时，接受辅助化疗的反应更好。这一观察结果表明，MUC2 参与了对氟尿嘧啶类辅助化疗的耐药性，可能是 II 期 CRC 患者有前途的未来预测生物标志物。
