ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.

The effect of cuproptosis-relevant genes on the immune infiltration and metabolism of gynecological oncology by multiply analysis and experiments validation.

Gynecological cancers are a leading cause of mortality for women, including ovarian cancer (OC), cervical squamous cell carcinoma (CESC), and uterine corpus endometrial carcinoma (UCEC). Nevertheless, these gynecological cancer types have not elucidated the role of cuproptosis and the correlated tumor microenvironment (TME) infiltration features. CRGs had important potential molecular functions and prognostic significance in gynecological cancers, especially in UCEC. Hub CRG, FDX1, was correlated with the CD8+ T cell immune infiltration in UCEC and CESC. FDX1 OE could significantly repress the proliferation ability in UCEC cells by MTT, EdU, and clone formation. High levels of FDX1 could repress ATP and lactic acid but enhance ROS and glucose levels by metabolism assay. The xenograft tumor model indicated that FDX1 OE significantly inhibited the growth of UCEC and attenuated the PCNA, HK2, PKM2, and Ki-67 expression. These CRGs are significant roles that could be potential markers and treatment targets to optimize the TME immune cell infiltration features for gynecological cancer types. FDX1 is a hub CRGs in UCEC to promote immune infiltration and attenuate proliferation and metabolism.

[Analysis of the security, pregnancy outcomes, and the tumor recurrence related factors of young patients with cervical cancer treated with different radical trachelectomy].

OBJECTIVE: To explore the security, pregnancy outcomes, and the tumor recurrence related factors of young patients with cervical cancer treated with different radical trachelectomy (RT). METHODS: Thirty-two young patients < 40 years of age with early cervical cancer from May 2004 to July 2012 admitted in Tumor Hospital Xiangya School of Medicine of Central South University were divided into two groups based on different operation methods: vaginal radical trachelectomy (RVT) group and abdominal radical trachelectomy (RAT) group.The clinical data were analyzed by One-way Anova and multivariate Cox stepwise regression analysis. RESULTS: The operation duration, number of lymph node dissection, the height of the cervical resection, postoperative hospitalization time, incidence of vascular injury and incidence of postoperative lymphocele were respectively (250 ± 82) min, 15 ± 6, (2.31 ± 0.21) cm, (9.2 ± 2.9) d, 1/18 and 1/18 in RVT group, while (263 ± 60) min,16 ± 8, (2.32 ± 0.26) cm, (10.3 ± 3.5) d,0 and 1/14 in RAT group. There was no statistically significant difference between the two groups (all P > 0.05). The blood loss (281 ± 201) ml in RVT group was significantly lower than that in the RAT group (492 ± 320) ml (P < 0.05). The length of Vaginal hysterectomy [(2.61 ± 0.50) cm] and the width of parametrial resection [ (2.38 ± 0.36) cm] in RVT group were significantly less than those [(2.95 ± 0.10), (2.81 ± 0.22) cm] in the RAT group (all P < 0.05).The pregnancy rate between RVT group (3/18) and RAT group (2/14) were no significant difference (P > 0.05).One-way Anova analysis showed that the recurrence of early cervical cancer was related to tumor size in diameter (F = 4.911, P = 0.047), while there were no correlation with age, clinical stage, histological type and surgical approach (all P > 0.05).Multivariate analysis showed that tumor diameter size was an independent risk factor for tumor recurrence (ß = 0.259, P = 0.031). CONCLUSIONS: RT for young patients with early cervical cancer is feasible.Pregnancy outcomes after RT need to be study in the future. Tumor size in diameter is the major risk factor for tumor recurrence.