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李佳丽, 徐晨, 张小垒, 等. KRAS基因突变亚型对直肠癌新辅助治疗后肿瘤退缩的影响[J]. 中国临床医学, 2024, 31(3): 389-393. DOI: 10.12025/j.issn.1008-6358.2024.20240246
引用本文: 李佳丽, 徐晨, 张小垒, 等. KRAS基因突变亚型对直肠癌新辅助治疗后肿瘤退缩的影响[J]. 中国临床医学, 2024, 31(3): 389-393. DOI: 10.12025/j.issn.1008-6358.2024.20240246
LI Jiali, XU Chen, ZHANG Xiaolei, et al. Effects of KRAS mutation variants on tumor regression grade of rectal cancer received neoadjuvant therapy[J]. Chinese Journal of Clinical Medicine, 2024, 31(3): 389-393. DOI: 10.12025/j.issn.1008-6358.2024.20240246
Citation: LI Jiali, XU Chen, ZHANG Xiaolei, et al. Effects of KRAS mutation variants on tumor regression grade of rectal cancer received neoadjuvant therapy[J]. Chinese Journal of Clinical Medicine, 2024, 31(3): 389-393. DOI: 10.12025/j.issn.1008-6358.2024.20240246

KRAS基因突变亚型对直肠癌新辅助治疗后肿瘤退缩的影响

Effects of KRAS mutation variants on tumor regression grade of rectal cancer received neoadjuvant therapy

  • 摘要:
    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淋巴细胞水平的关系。
    结果 共纳入95例患者,其中肿瘤退缩不良患者55例。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突变的发生率高于肿瘤退缩显著患者(P<0.05)。KRAS基因G12D突变的患者中,肿瘤退缩不良者肿瘤组织学分级高于肿瘤退缩显著者(P=0.027)。肿瘤退缩不良患者中,KRAS基因G12D突变者肿瘤CD8+、PD-1+ T淋巴细胞浸润水平高于G12V、G13D突变患者(P<0.05)。
    结论 KRAS基因G12V突变和A146突变提示直肠癌新辅助治疗效果不佳;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+ T淋巴细胞浸润水平,筛选免疫治疗的潜在获益者。

     

    Abstract:
    Objective To investigate the effects of KRAS mutation isoforms on tumor regression grade (TRG) of rectal cancer received neoadjuvant therapy.
    Methods The clinicopathologic data of patients with locally advanced and metastatic rectal cancer (stage Ⅲ-Ⅳ) who underwent radical tumor resection after neoadjuvant therapy were collected. The correlations between the mutated subtypes of KRAS and TRG as well as the clinicopathological features were analyzed.
    Results A total of 95 patients were enrolled, including 55 patients with poor tumor regression. The incidences of G12V mutation in exon 2 and A146 mutation in exon 4 of the KRAS gene were higher in the group with poor tumor regression than those in the significant tumor regression group (P < 0.05). In patients with G12D mutation of KRAS gene, the histological grade of tumor in poor tumor regression was higher than that in significant tumor regression group (P=0.027). In patients with poor tumor regression, the levels of CD8+, PD-1+ T-lymphocyte infiltration were higher in G12D mutation subgroup than those in G12V mutation and G13D mutation subgroups (P < 0.05).
    Conclusions KRAS G12V mutation and A146 mutation suggest poor neoadjuvant therapy effect for rectal cancer; for patients with KRAS G12D mutation and poor tumor regression, the potential beneficiary for immunotherapy would be screened by detecting CD8+ and PD-1+ T-lymphocyte infiltration.

     

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