Author(s)

ZhiGang Zhai¹, Yuan Fang¹, ZhenYu Xue¹, Jian Guo², Wen Sun¹, Xiang Tang^1*

Affiliation(s)

¹Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.

²Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.

Corresponding Author

Xiang Tang

ABSTRACT

Objective: To analyze the expression of TREM1 in gastric cancer tissues and serum of gastric cancer patients, and to explore the link between TREM1 expression levels and the clinical features of patients. Furthermore, to explore the specific mechanism by which TREM1 promotes the metastatic ability of MKN45 cells. Method: Gene expression analysis, differential genes, KEGG enrichment analysis, and immune correlation analysis were performed using TCGA and GEO databases; Compare the concentration of TREM1 in the serum of gastric cancer patients using clinical serum sample standards and group them to analyze the relationship between TREM1 and clinical characteristics and prognosis of patients; Select MKN45 cells, silence the expression of TREM1 and IL-6 using small interfering RNA, overexpress TREM1 using plasmid, and perform corresponding treatments. Compare the changes in cell proliferation and migration ability in different groups using scratch assay and transwell assay; Western blotting was used to detect changes in the ERK signaling pathway, IL-6 expression, and EMT related proteins among different groups; Real time fluorescence quantitative PCR comparison of changes in downstream immune factors of TREM1. Result: TREM1 concentration increased in the serum of gastric cancer patients and was associated with their recurrence, metastasis, and overall survival time; TREM1 promotes invasion and metastasis of MKN45 cells; TREM1 upregulates IL-6 by activating the ERK signaling pathway; TREM1 promotes gastric cancer EMT by upregulating IL-6, leading to enhanced metastatic ability of gastric cancer cells. Conclusion: TREM1 is highly expressed in the serum of gastric cancer patients and upregulates IL-6 by activating the ERK signaling pathway, thereby promoting EMT and invasion and metastasis of gastric cancer, leading to poor prognosis for patients.

KEYWORDS

TREM1; IL-6; Gastric cancer; EMT; ERK signaling pathway; Recurrence and metastasis

CITE THIS PAPER

ZhiGang Zhai, Yuan Fang, ZhenYu Xue, Jian Guo, Wen Sun, Xiang Tang. TREM1 promotes gastric cancer metastasis and leads to poor prognosis in patients through the ERK/IL-6 signaling pathway. Journal of Pharmaceutical and Medical Research. 2026, 8(1): 8-15. DOI: https://doi.org/10.61784/jpmr3062.

REFERENCES

[1] Xin Z, Jiao M, Mengying C, et al. Investigation on the mechanism of Shaoyao-Gancao Decoction in the treatment of gastric carcinoma based on network pharmacology and experimental verification. Aging (Albany NY), 2023, 15(1).

[2] Kejia M, Xuejie C, Xin X, et al. Willingness to Undergo Gastroscopy for Early Gastric Cancer Screening and Its Associated Factors During the COVID-19 Pandemic - A Nationwide Cross-Sectional Study in China. Patient Prefer Adherence, 2023, 17(0).

[3] Bingfeng H, Rongshou Z, Hongmei Z, et al. Cancer incidence and mortality in China, 2022. Journal of the National Cancer Center, 2024, 4(1).

[4] Hoon H, Young Joon L, Young-Woo K, et al. Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial. Ann Surg, 2024.

[5] Jiaoyu A, Wanlin Z, Wensheng D, et al. A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma. BMC Cancer, 2024, 24(1).

[6] Takuro S, Yukinori K, Kazumasa F, et al. Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study. British Journal of Cancer, 2024, 130(7).

[7] Sarah S K Y, Yin T, Hoi Cheong S, et al. Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression. Gut, 2024, 74(4).

[8] Tadahito Y, Y Alan W. Gastric cancer immunosuppressive microenvironment heterogeneity: implications for therapy development. Trends Cancer, 2024, 10(7).

[9] Mingguang J, Zhizhong J, XUE Y, et al. Gastric Cancer Models Developed via GelMA 3D Bioprinting Accurately Mimic Cancer Hallmarks, Tumor Microenvironment Features, and Drug Responses. Small, 2025, 21(8).

[10] Li L, Wenxuan L, Wenhong D. Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway. Annals of Medicine, 2025, 57(1).

[11] Long-Long D, Meng Z, Tao Z, et al. MFGE8 promotes gastric cancer progression by activating the IL-6/JAK/STAT3 signaling. Cell Signal, 2024, 125(0).

[12] Mengyun Y, Xi Z, Shenlin L, et al. Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ. Biomed Pharmacother, 2020, 129.

[13] Marine J, Gorann L, Lucie B, et al. Effect of Lactobacillus gasseri BIO6369 and Lacticaseibacillus rhamnosus BIO5326 on Gastric Carcinogenesis Induced by Helicobacter pylori Infection. Helicobacter, 2024, 29(4).

[14] Joao V B C, Maria M B M D S, Wilma T F V, et al. Sepsis Prediction: Biomarkers Combined in a Bayesian Approach. International Journal of Molecular Sciences, 2025, 26(15).

[15] Yuan C, Jiancong C, Yuqin P, et al. Gut-derived macrophages link intestinal damage to brain injury after cardiac arrest through TREM1 signaling. Cellular & Molecular Immunology, 2025, 22(4).

[16] Ashwin A, Kenza M, Daniel D H, et al. Targeting TREM1 augments antitumor T cell immunity by inhibiting myeloid-derived suppressor cells and restraining anti-PD-1 resistance. Journal of Clinical Investigation, 2023, 133(21).

[17] Yang Z, Hong-Jun L, Xue-Yang D, et al. Translocated HMGB3 is involved in papillary thyroid cancer progression by activating cytoplasmic TLR3 and transmembrane TREM1. Cell Cycle, 2024, 22.

[18] Zhulin Y, Wei Z, Keyu S. TREM1 is involved in the mechanism between asthma and lung cancer by regulating the Toll-like receptor signaling pathway. Oncology Letters, 2023, 27(1).

[19] Salvatore L, Giuseppe S, Maria Grazia C, et al. Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation. Frontiers in Immunology, 2020, 10(0).

[20] Keying C, Yuting L, Xueru S, et al. Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer. EMBO Molecular Medicine, 2024, 16(2).

[21] Yang L, Lili N, Qiang L, et al. Identification of an immune-related eRNA prognostic signature for clear cell renal cell carcinoma. Aging (Albany NY), 2024, 16(3).

[22] Lornella S, Emilie B, Francis M, et al. Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies. International Journal of Molecular Sciences, 2021, 22(7).

[23] Hadrien D B, Laurie T, Frédérique F, et al. Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity. Science Advances, 2024, 10(7).

[24] Cagri C, Benay D, Ruveyde Safiye U, et al. LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer. Journal of Cancer, 2024, 15(3).

[25] Wenfeng L, Haiqing J, Hao X, et al. High KRT17 expression in tumour budding indicates immunologically 'hot' tumour budding and predicts good survival in patients with colorectal cancer. Clinical and Translational Immunology, 2024, 13(3).