KRAS基因突变亚型与直肠癌新辅助治疗后肿瘤退缩的相关性分析

目的 探讨KRAS基因突变亚型与直肠癌新辅助治疗后肿瘤退缩反应及临床病理特征等的相关性。方法 收集新辅助治疗后行肿瘤根治术的局部晚期和转移性直肠癌（III-IV期）患者的临床病理资料,分析KRAS基因突变亚型与肿瘤退缩反应以及残余肿瘤组织学分级、肿瘤浸润T淋巴细胞的相关性。结果 共纳入95例新辅助治疗后的III-IV期直肠癌患者,结果显示肿瘤退缩不良患者KRAS基因第2外显子G12V突变和第4外显子A146突变的发生率显著高于肿瘤退缩显著患者（P=0.037,P=0.048）。并且,KRAS基因G12D突变的肿瘤退缩不良患者,其组织学分级显著高于肿瘤退缩显著患者（P=0.027）。此外,KRAS基因G12D突变的肿瘤退缩不良患者,CD8+、PD-1+的肿瘤相关T淋巴细胞浸润显著高于G12V、G13D突变患者（P<0.05）。结论 KRAS基因G12V突变和A146突变高度提示直肠癌新辅助治疗效果不佳,精准检测KRAS基因突变亚型对于预测新辅助治疗效果并指导临床治疗至关重要。此外,对于肿瘤退缩不良的KRAS基因G12D突变患者,可通过检测CD8+、PD-1+的肿瘤相关T淋巴细胞浸润,筛选免疫治疗的潜在获益人群。

Association of KRAS mutation variants with TRG in resected rectal cancer received adjuvant chemotherapy

Objective To investigate the association of KRAS mutation isoforms with TRG in resected rectal cancer received adjuvant therapy. Methods The mutated subtypes of RAS gene were detected in the residual tumors after neoadjuvant therapy by Next-Generation Sequencing (NGS), and then to analyze the correlation between the mutated subtypes and tumor regression as well as the clinicopathological features. Results A total of 95 patients of stage III-IV rectal cancer after neoadjuvant therapy were included, and it was found that the incidence of G12V mutation in exon 2 and A146 mutation in exon 4 of the KRAS gene were significantly higher in the group with poor tumor regression than the significant tumor regression group(P=0.037, P=0.048). Moreover, for patients with G12D mutation of KRAS gene, the histological differentiation with poor tumor regression was significantly worse than that of the group with significant tumor regression. In addition, CD8+, PD-1+ T-lymphocyte infiltration was significantly higher in poor tumor regression patients with G12D mutation than in patients with G12V and G13D mutations(P<0.05). Conclusions KRAS G12V mutation and A146 mutation are highly suggestive of poor neoadjuvant therapy for rectal cancer, and accurate detection of KRAS gene mutation subtypes is crucial for predicting the effect of neoadjuvant therapy and guiding clinical treatment. In addition, for patients of KRAS G12D mutation with poor tumor regression, the potential beneficiary population of immunotherapy would be screened by detecting CD8+ and PD-1+ T-lymphocyte infiltration.