Changlin Zhang

Clinicopathologic and prognostic significance of tumor-associated macrophages in cervical cancer: a systematic review and meta-analysis

Abstract Objectives The role of tumor-associated macrophages (TAMs) in cervical cancer (CC) remains controversial. Here, we report a meta-analysis of the association between TAMs infiltration and clinical outcomes. Methods PubMed, Embase, Web of Science, and CNKI were searched systematically from inception until December 20, 2023. Studies involving TAMs and prognosis, clinical, or pathological features were included. Quality assessments of the selected studies were assessed. The fixed-effect or random-effects model, standard mean difference (SMD), odds ratios (OR), or hazard ratios (HR) with 95% confidence intervals (CIs) were used as the effect size estimate. Results 26 eligible studies with 2,295 patients were identified. Our meta-analysis revealed that TAMs were overexpressed in CC (OR = 12.93, 95% CI = 7.73–21.61 and SMD = 1.58, 95% CI = 0.95–2.21) and that elevated TAM levels were strongly associated with lymph node metastasis (LNM) (SMD = 0.51, 95% CI = 0.90–2.01) and FIGO stages (SMD = 0.46, 95% CI = 0.08–0.85). Subgroup analysis indicated a significant positive correlation between LNM and TAMs density in tumor stroma, but not in cancer nests (SMD = 0.58, 95% CI = 0.31–0.58). Furthermore, in early stage, a stronger correlation exists between LNM and TAM density (SMD = 1.21, 95% CI = 0.75–1.66). In addition, it revealed that patients with high TAMs expression had poorer overall survival (OS) (HR = 2.55 95% CI = 1.59–4.07) and recurrence-free survival (RFS) (HR = 2.17, 95% CI = 1.40–3.35). Conclusions Our analyses suggest that a high density of TAMs predicts adverse outcomes in CC.

Upregulation of FAM83F by c-Myc promotes cervical cancer growth and aerobic glycolysis via Wnt/β-catenin signaling activation

AbstractCervical cancer (CC) seriously affects women’s health. Therefore, elucidation of the exact mechanisms and identification of novel therapeutic targets are urgently needed. In this study, we identified FAM83F, which was highly expressed in CC cells and tissues, as a potential target. Our clinical data revealed that FAM83F protein expression was markedly elevated in CC tissues and was positively correlated with poor prognosis. Moreover, we observed that FAM83F knockdown significantly inhibited cell proliferation, induced apoptosis, and suppressed glycolysis in CC cells, while its overexpression displayed opposite effects. Mechanistically, FAM83F regulated CC cell growth and glycolysis by the modulation of Wnt/β-catenin pathway. The enhancing effects of FAM83F overexpression on CC cell proliferation and glycolysis could be impaired by the Wnt/β-catenin inhibitor XAV939. Moreover, we found that c-Myc bound to the FAM83F promoter and activated the transcription of FAM83F. Notably, knockdown of FAM83F impaired the enhancement of cell proliferation and glycolysis induced by ectopic c-Myc. Consistent with in vitro findings, results from a xenograft mouse model confirmed the promoting role of FAM83F. In summary, our study demonstrated that FAM83F promoted CC growth and glycolysis through regulating the Wnt/β-catenin pathway, suggesting that FAM83F may be a potential molecular target for CC treatment.

Jagged1 contained in MSC-derived small extracellular vesicles promotes squamous differentiation of cervical cancer by activating NOTCH pathway

Abstract Purpose Cervical cancer is the fourth most common cancer in women and poses a major threat to women's health, urgently requiring new treatment methods. Methods This study first successfully extracted and identified small extracellular vesicles secreted by human umbilical cord-derived mesenchymal stem cells. We studied the effects of MSC-sEV on the squamous differentiation levels of cervical cancer CaSki cells in vitro, and explored the effects of MSC-sEV on the NOTCH pathway, the growth, proliferation, migration abilities and squamous differentiation levels of cervical cancer cells. The roles of MSC-sEV were also verified in human keratinocyte HaCaT cells. Results The results showed that Jagged1 protein on MSC-sEV can bind to NOTCH1 on cervical cancer cells, activate NOTCH signaling, and promote squamous differentiation levels in CaSki cells, thus inhibiting the growth, proliferation and migration abilities of CaSki cells. MSC-sEV can also activate the NOTCH pathway in HaCaT cells, but promote the viability of HaCaT cells. Conclusion MSC-sEV can activate the NOTCH pathway to promote squamous differentiation of CaSki cells and inhibit the growth proliferation and migration abilities of CaSki cells which may be a new mechanism for cervical cancer treatment.