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

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.