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KRAS表达与结直肠癌中KRAS状态、预后及肿瘤浸润性T淋巴细胞的关系。

The relationship of KRAS expression with KRAS status, prognosis, and tumor-infiltrated T lymphocytes in colorectal cancer.

作者信息

Zhou Yebohao, Zeng Ziwei, Li Ze, Ruan Lei, Xie Hao, Ye Fujin, Huang Liang, Liu Huashan, Kang Liang

机构信息

Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, China.

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Therap Adv Gastroenterol. 2024 May 15;17:17562848241249387. doi: 10.1177/17562848241249387. eCollection 2024.

Abstract

BACKGROUND

The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied.

OBJECTIVE

To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC.

DESIGN

Single-center retrospective study.

METHODS

Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes.

RESULTS

This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status ( > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival ( < 0.05). Subgroup analysis revealed that high KRAS expression remained indicative of a worse prognosis in the group with mismatch repair-deficient (dMMR) and KRAS mutant type ( < 0.05). Multivariate analysis confirmed KRAS expression as an unfavorable prognostic factor ( < 0.05). However, the significance of KRAS expression was lost in the dMMR and KRAS mutant-type group regarding overall survival ( > 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue ( < 0.05), a finding also observed in the dMMR group ( < 0.05).

CONCLUSION

No association was found between KRAS expression and KRAS mutation status in CRC. Higher KRAS expression was indicative of poorer prognosis for CRC patients, except for those with proficient mismatch repair and KRAS wild type. In addition, in patients with dMMR, KRAS expression was associated with a lower density of CD8+ T lymphocytes in tumor tissue.

摘要

背景

Kirsten大鼠肉瘤病毒癌基因(KRAS)突变在结直肠癌(CRC)中的意义已得到充分证实;然而,其与KRAS表达及预后的关系仍需进一步研究。虽然KRAS高表达在其他癌症中通常与较差的预后相关,但其在结直肠癌中的作用仍相对研究较少。

目的

探讨结直肠癌中KRAS表达、KRAS状态、预后与肿瘤浸润性T淋巴细胞密度之间的相关性。

设计

单中心回顾性研究。

方法

本研究于2010年至2020年期间进行,利用肿瘤样本评估KRAS表达并量化CD3+/CD8+ T淋巴细胞。采用Cox比例风险模型和线性回归分析来研究KRAS表达、预后与肿瘤浸润性T淋巴细胞之间的关系。

结果

本研究纳入了265例行根治性手术的结直肠癌患者。未观察到KRAS表达与KRAS状态之间存在显著关联(>0.05)。KRAS高表达与较差的总生存期和无病生存期相关(<0.05)。亚组分析显示,在错配修复缺陷(dMMR)和KRAS突变型组中,KRAS高表达仍表明预后较差(<0.05)。多因素分析证实KRAS表达是一个不良预后因素(<0.05)。然而,在dMMR和KRAS突变型组中,KRAS表达对总生存期的意义消失(>0.05)。值得注意的是,KRAS表达与肿瘤组织中CD8+ T淋巴细胞密度呈负相关(<0.05),在dMMR组中也观察到这一结果(<0.05)。

结论

在结直肠癌中未发现KRAS表达与KRAS突变状态之间存在关联。除错配修复功能正常和KRAS野生型的患者外,KRAS高表达表明结直肠癌患者预后较差。此外,在dMMR患者中,KRAS表达与肿瘤组织中CD8+ T淋巴细胞密度较低有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b433/11097731/4edc47d0edcb/10.1177_17562848241249387-fig1.jpg

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