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Abstract：
BACKGROUND: More than half of the patients with locally advanced low rectal cancer exhibit no or minor response to nCRT. It is important to investigate the predictive and prognostic values of potential biomarkers in patients with locally advanced low rectal cancer receiving nCRT.
METHODS: This retrospective study included 162 patients with locally advanced low rectal cancer who underwent nCRT, followed by total mesorectal excision (TME) between 2016 and 2019. Cytokeratin 7 (CK7) expression and mismatch repair (MMR) status were determined by immunohistochemistry (IHC). Categorical variables were compared using the chi-square test. Overall survival (OS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier and Cox methods.
RESULTS: There were predominance significant differences in distance from anus margin (P < .0001) and circumferential extent of the tumor (P < .0001).CK7 positive expression was detected in 21 of the 162 patients (13%). The univariate and multivariate analysis revealed that patients whose tumors had CK7 positive expression had significantly shorter OS (HR = 3.878, P = .038; HR = 1.677, P = .035) and DFS (HR = 3.055, P = .027;HR = 3.569, P = .038) than those with CK7 negative expression. While patients with CK7 positive expression had a higher proportion of worse TRG compared with CK7 negative patients (P = .001). Patients with deficient mismatch repair (dMMR) just occupied a small proportion (8.6%), but there was still a close connection between the MMR status and recurrence after TME (P = .045). MMR status was an independent risk factor affecting the OS (HR = .307, P < .0001; HR = .123, P < .0001) and DFS (HR = .288, P < .0001; HR = .286, P < .0001) by univariate and multivariate analysis. But no significant difference in the proportion of TRG was observed between patients with dMMR and pMMR (P = .920).
CONCLUSIONS: The result confirms negative prognostic role of CK7-positive and dMMR statuses, which have potential predictive value for neoadjuvant chemoradiotherapy response. This provides opportunity to modify individualized treatment strategies for patients with different CK7 expression levels and dMMR statuses.
METHODS: This retrospective study included 162 patients with locally advanced low rectal cancer who underwent nCRT, followed by total mesorectal excision (TME) between 2016 and 2019. Cytokeratin 7 (CK7) expression and mismatch repair (MMR) status were determined by immunohistochemistry (IHC). Categorical variables were compared using the chi-square test. Overall survival (OS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier and Cox methods.
RESULTS: There were predominance significant differences in distance from anus margin (P < .0001) and circumferential extent of the tumor (P < .0001).CK7 positive expression was detected in 21 of the 162 patients (13%). The univariate and multivariate analysis revealed that patients whose tumors had CK7 positive expression had significantly shorter OS (HR = 3.878, P = .038; HR = 1.677, P = .035) and DFS (HR = 3.055, P = .027;HR = 3.569, P = .038) than those with CK7 negative expression. While patients with CK7 positive expression had a higher proportion of worse TRG compared with CK7 negative patients (P = .001). Patients with deficient mismatch repair (dMMR) just occupied a small proportion (8.6%), but there was still a close connection between the MMR status and recurrence after TME (P = .045). MMR status was an independent risk factor affecting the OS (HR = .307, P < .0001; HR = .123, P < .0001) and DFS (HR = .288, P < .0001; HR = .286, P < .0001) by univariate and multivariate analysis. But no significant difference in the proportion of TRG was observed between patients with dMMR and pMMR (P = .920).
CONCLUSIONS: The result confirms negative prognostic role of CK7-positive and dMMR statuses, which have potential predictive value for neoadjuvant chemoradiotherapy response. This provides opportunity to modify individualized treatment strategies for patients with different CK7 expression levels and dMMR statuses.
摘要：
背景：超过一半的局部晚期低位直肠癌患者对nCRT无反应或反应较小。研究潜在生物标志物在接受nCRT的局部晚期低位直肠癌患者中的预测和预后价值非常重要。
方法：这项回顾性研究纳入了162例接受nCRT治疗的局部晚期低位直肠癌患者，其次是2016年至2019年的全直肠系膜切除术（TME）。通过免疫组织化学(IHC)确定细胞角蛋白7(CK7)表达和错配修复(MMR)状态。使用卡方检验比较分类变量。使用Kaplan-Meier和Cox方法估计总生存期(OS)和无病生存期(DFS)曲线。
结果：与肛门边缘的距离（P<0.0001）和肿瘤的圆周范围（P<0.0001）存在显着差异。162例患者中有21例(13%)检测到CK7阳性表达。单因素和多因素分析显示，CK7阳性表达患者的OS（HR=3.878，P=.038；HR=1.677，P=.035）和DFS（HR=3.055，P=.027；HR=3.569，P=.038）明显短于CK7阴性表达患者。与CK7阴性患者相比，CK7阳性表达患者TRG较差的比例更高（P=0.001）。缺陷错配修复（dMMR）的患者仅占一小部分（8.6％），但MMR状态与TME后复发之间仍然存在密切联系(P=.045).通过单因素和多因素分析，MMR状态是影响OS（HR=.307，P<.0001；HR=.123，P<.0001）和DFS（HR=.288，P<.0001；HR=.286，P<.0001）的独立危险因素。但是在dMMR和pMMR患者中，TRG的比例没有显着差异（P=0.920）。
结论：结果证实了CK7阳性和dMMR状态的负面预后作用，对新辅助放化疗反应具有潜在的预测价值。这为具有不同CK7表达水平和dMMR状态的患者提供了修改个体化治疗策略的机会。
方法：这项回顾性研究纳入了162例接受nCRT治疗的局部晚期低位直肠癌患者，其次是2016年至2019年的全直肠系膜切除术（TME）。通过免疫组织化学(IHC)确定细胞角蛋白7(CK7)表达和错配修复(MMR)状态。使用卡方检验比较分类变量。使用Kaplan-Meier和Cox方法估计总生存期(OS)和无病生存期(DFS)曲线。
结果：与肛门边缘的距离（P<0.0001）和肿瘤的圆周范围（P<0.0001）存在显着差异。162例患者中有21例(13%)检测到CK7阳性表达。单因素和多因素分析显示，CK7阳性表达患者的OS（HR=3.878，P=.038；HR=1.677，P=.035）和DFS（HR=3.055，P=.027；HR=3.569，P=.038）明显短于CK7阴性表达患者。与CK7阴性患者相比，CK7阳性表达患者TRG较差的比例更高（P=0.001）。缺陷错配修复（dMMR）的患者仅占一小部分（8.6％），但MMR状态与TME后复发之间仍然存在密切联系(P=.045).通过单因素和多因素分析，MMR状态是影响OS（HR=.307，P<.0001；HR=.123，P<.0001）和DFS（HR=.288，P<.0001；HR=.286，P<.0001）的独立危险因素。但是在dMMR和pMMR患者中，TRG的比例没有显着差异（P=0.920）。
结论：结果证实了CK7阳性和dMMR状态的负面预后作用，对新辅助放化疗反应具有潜在的预测价值。这为具有不同CK7表达水平和dMMR状态的患者提供了修改个体化治疗策略的机会。
