PLA1A在结直肠癌中的表达与临床病理及免疫浸润的相关性分析

Correlation of PLA1A expression level with clinicopathological features and immune infiltration in colorectal cancer

  • 摘要:
    目的 探讨磷脂酰丝氨酸特异性磷脂酶A1(phosphatidylserine-specific phospholipase A1,PLA1A)在结直肠癌(colorectal cancer,CRC)中的表达并分析其与临床病理特征、预后及免疫浸润之间的相关性。
    方法 采用生物信息学方法筛选并分析PLA1A在CRC中的表达及对患者预后的影响。选取2020年1月至2020年12月于山西省肿瘤医院确诊为CRC的患者共192例,采用免疫组织化学(immunohistochemistry ,IHC)和实时荧光定量逆转录PCR(real-time quantitative reverse transcription PCR,RT-qPCR)法检测PLA1A在CRC中的表达情况,通过χ2检验分析PLA1A与CRC患者临床病理特征的关系;IHC检测CRC中免疫细胞标记物CD4、CD8及抑制性免疫检查点PD-1、TIM-3、CTLA-4的表达,χ2检验分析其与PLA1A的相关性。
    结果 生物信息学分析结果显示PLA1A在CRC中的表达高于癌旁组织,且与总生存期(overall survival ,OS)相关(P<0.05)。IHC和RT-qPCR结果显示PLA1A在CRC中显著高表达(P<0.05),PLA1A高表达与TNM分期、分化程度及淋巴结转移密切相关(P<0.05)。IHC结果显示PLA1A与CD8+T细胞浸润水平呈正相关(P<0.05)。此外,高水平PLA1A会上调免疫抑制性检查点PD-1、TIM-3、CTLA-4的表达(P<0.05)。
    结论 PLA1A在CRC中高表达,与免疫浸润细胞和免疫抑制性检查点密切相关,提示其在CRC免疫浸润中的重要作用,对CRC的治疗具有指导意义。

     

    Abstract:
    Objective  This study investigated the expression level of phosphatidylserine-specific phospholipase A1 (PLA1A) in colorectal cancer (CRC) and analyzed its correlations with clinicopathological features, prognosis, and immune infiltration.
    Methods The expression level of PLA1A in CRC was screened, and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods. A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected. The PLA1A expression level in those with CRC was determined using immunohistochemistry (IHC) and real-time quantitative reverse transcription PCR (RT-qPCR). The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test. The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1, TIM-3, and CTLA-4 in CRC were detected via IHC, and their correlations with PLA1A level were analyzed using the chi-square test.
    Results The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue, which correlated with overall survival (OS) (P<0.05). The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue (P<0.05). High PLA1A level was closely associated with the TNM stage, degree of differentiation, and lymph node metastasis (P<0.05). The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level (P<0.05). In addition, the elevated PLA1A levels upregulated the expressions of immunosuppressive checkpoints PD-1, TIM-3, and CTLA-4 (P<0.05).
    Conclusions PLA1A is highly expressed in CRC, which is closely related to immune infiltrating cells and immunosuppressive checkpoints, suggesting that PLA1A plays an important role in immune infiltration in CRC, a finding that provides guidance in the treatment of CRC.

     

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