关键词: colorectal cancer immune checkpoint proteins microsatellite instability (msi) mmr status programmed death ligand-1

来  源:   DOI:10.7759/cureus.43571   PDF(Pubmed)

Abstract:
Introduction Colorectal cancer (CRC) is the third most common cancer in the world among men and second among women worldwide. One of the major molecular pathways responsible for the development of colorectal cancer (CRC) is the microsatellite instability (MSI) pathway. During carcinogenesis, the tumor cells express programmed death ligand-1 (PD-L1), which reduces the immunogenicity leading to the escape of immune attack. Anti-PD-L1 interaction is an upcoming line of research for the treatment of colorectal carcinoma patients. Materials and methods The present study was an ambispective study where the mismatch repair deficiency status (MMR) and programmed death ligand-1 (PD-L1) expression were studied using immunohistochemistry and then later analyzed and compared with the clinicopathological parameters and MSI status in relation to the expression of programmed death ligand-1 (PD-L1) in neoplastic and immune cells in a total of 55 biopsy specimen. MMR expression was reported as retained or loss of nuclear staining, and PD-L1 expression was taken as positive with a cut-off of more than or equal to 5% membranous positivity in both tumor cells and immune cells. Results The analysis showed a significant correlation of microsatellite instability (MSI) status with two of the clinicopathological parameters, which were the site of the tumor (p-value<0.001) and M stage (p-value<0.001). PD-L1 expression in neoplastic cells showed no significant correlation with the clinicopathological parameters, whereas PD-L1 expression in immune cells showed a significant association with gender (p-value=0.043). Also, MSI status showed a significant association with PD-L1 expression in tumor cells (p-value <0.001).
摘要:
背景技术结肠直肠癌(CRC)是世界上男性中的第三大最常见的癌症,并且是世界上女性中的第二大癌症。导致结直肠癌(CRC)发展的主要分子途径之一是微卫星不稳定性(MSI)途径。在致癌过程中,肿瘤细胞表达程序性死亡配体-1(PD-L1),这降低了导致免疫攻击逃避的免疫原性。抗PD-L1相互作用是即将到来的治疗结直肠癌患者的研究路线。材料和方法本研究是一项双向研究,其中使用免疫组织化学研究了错配修复缺陷状态(MMR)和程序性死亡配体1(PD-L1)的表达,然后进行了分析,并与临床病理参数和MSI状态进行了比较。在总共55个活检标本中,与肿瘤和免疫细胞中程序性死亡配体1(PD-L1)的表达有关。MMR表达被报道为保留或丢失核染色,PD-L1表达为阳性,在肿瘤细胞和免疫细胞中均显示大于或等于5%的膜阳性。结果分析显示微卫星不稳定性(MSI)状态与两个临床病理参数有显著相关性,即肿瘤部位(p值<0.001)和M期(p值<0.001)。PD-L1在肿瘤细胞中的表达与临床病理参数无显著相关性,而免疫细胞中PD-L1的表达与性别显著相关(p值=0.043).此外,MSI状态显示与肿瘤细胞中PD-L1表达显著相关(p值<0.001)。
公众号