基于胃癌小鼠中的蛆活性化合物和多酚混合物,进行系统生物学分析,以开发诊断生物标志物、监测病理指标和新的免疫靶向治疗方法。
System biology analysis to develop diagnostic biomarkers, monitoring pathological indexes, and novel therapeutic approaches for immune targeting based on maggot bioactive compounds and polyphenolic cocktails in mice with gastric cancer.
发表日期:2023 Sep 22
作者:
Elina Kaviani, Fatemeh Hajibabaie, Navid Abedpoor, Kamran Safavi, Zahra Ahmadi, Azadeh Karimy
来源:
ENVIRONMENTAL RESEARCH
摘要:
胃癌(GaCa)的早期诊断和预后是减少死亡率的先决条件。对一些引起或敏感的元素(编码RNA(cRNA)-非cRNA(ncRNA))进行鉴定可以在早期诊断胃癌方面非常有帮助。值得注意的是,尽管胃癌治疗取得了显著进展,但患者的预后仍不令人满意,原因包括多药耐药和肿瘤复发等限制。因此,对辅助疗法和补充剂的研究越来越受到关注。在这方面,通过联合化疗(紫杉醇)与多酚类天然化合物(PNC)和蛆虫幼虫(MaLa)同时给予N-甲基-N-亚硝基脲(MNU)诱导的小鼠肿瘤模型。此外,为了鉴定潜在的诊断或预后生物标志物,通过生物信息学方法进行转录组学分析。然后通过qPCR实时、Western blot和ELISA评估ncRNA的转录谱与其靶标基因。根据生物信息学结果,发现17个与炎症和氧化应激以及胃癌发展有关(例如,IL-6、CXCL8、MKI67、IL-2、IL-4、IL-10、IL-1β、SPP1、LOX、COL1A1和IFN-γ)的核心基因。同时还确定了这些核心基因之上的调控因子(lncRNA XIST和NEAT1),并将其作为胃癌的预后和诊断生物标志物介绍出来。我们的研究结果表明,PNC单独或与MaLa联合可以减小肿瘤的大小和数量,这与基因表达水平(包括IL-6、CXCL8、MKI67、IL-2、IL-4、IL-10、IL-1β、SPP1、LOX、COL1A1、IFN-γ、NEAT1和XIST)的降低有关。总之,PNC和MaLa具有作为辅助并改善化疗的潜力,因为它们含有有效的化合物。此外,引入的核心基因和lncRNA除了作为诊断和预后生物标志物外,还可以作为胃癌的治疗靶点蛋白。版权所有 © 2023. Elsevier Inc.发表。
Early diagnosis and prognosis are prerequisites for mitigating mortality in gastric cancer (GaCa). Identifying some causative or sensitive elements (coding RNA (cRNA)-non-cRNAs (ncRNAs)) can be very helpful in the early diagnosis of GaCa. Notably, despite significant development in the GaCa treatment, the outcome of patients does not remain satisfactory due to limitations such as multi-drug resistance and tumor relapse. Therefore, more attention has been drawn to complementary therapies and the use of supplements. In this regard, Polyphenol natural compounds (PNC) and maggot larvae (MaLa) alone or in combination were administered along with chemotherapy (paclitaxel) to N-methyl-N-nitrosourea (MNU)- induced murine tumor model. In addition, in order to identify potential diagnostic or prognostic biomarkers, transcriptomics analysis was performed through a bioinformatics approach. Then transcription profile of ncRNAs with their target hub genes was assessed through qPCR Real-Time, Western blot, and ELISA. According to the bioinformatics results, 17 hub genes (e.g., IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1β, SPP1, LOX, COL1A1, and IFN-γ) were explored that contribute towards inflammation and oxidative stress and ultimately GaCa development. Upstream of the mentioned hub genes, regulatory factors (lncRNA XIST and NEAT1) were also identified and introduced as prognosis and diagnosis biomarkers for GaCa. Our results showed that PNC alone and in combination with MaLa was able to reduce the size and number of tumors, which is related to the reduction of genes expression levels (including IL-6, CXCL8, MKI67, IL-2, IL-4, IL-10, IL-1β, SPP1, LOX, COL1A1, IFN-γ, NEAT1, and XIST). In conclusion, PNC and MaLa have the potential to be considered as complementary and improving chemotherapy due to their effective compounds. Also, the introduced hub gene and lncRNA in addition to diagnostic and prognostic biomarkers can be used as druggable proteins for novel therapeutic targeting of GaCa.Copyright © 2023. Published by Elsevier Inc.