Annexin A5 is a novel prognostic biomarker in oral squamous cell carcinoma.

BACKGROUND: ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values. METHODS: 520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi-square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan-Meier method and log-rank test. RESULTS: Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non-tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast-like cells but absent in tumor-infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast-like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial-mesenchymal transformation (EMT), TGF-beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC. CONCLUSION: ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway.

Augmentation of hepatocellular carcinoma malignancy by annexin A5 through modulation of invasion and angiogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) continues to play a substantial role in cancer-related morbidity and mortality, largely owing to its pronounced tumor heterogeneity and propensity for recurrence. This underscores the pressing need for in-depth examination of its highly malignant mechanisms. Annexin A5 (ANXA5), recognized as a hallmark tumor protein, has emerged as a focal point of interest because of its ambiguous function and mechanism in HCC prognosis. This study aimed to provide a comprehensive understanding of the role of ANXA5 in the malignant progression of human HCC cells by employing an integrative approach that combines conventional experimental methods with RNA sequencing. METHODS: Differences in ANXA5 expression between HCC tissues and corresponding nontumor tissues were evaluated using immunofluorescence (n = 25). Correlation analysis was subsequently performed to assess the association between ANXA5 expression and clinicopathological features (n = 65). The role of ANXA5 in human HCC cell lines with ANXA5 gene knockout and overexpression was explored in vitro using migration and invasion assays and Ki-67 indices and in vivo based on node mice xenograft model. A tube formation assay using human umbilical vein endothelial cells (HUVECs) was conducted to demonstrate the angiogenic effects of ANXA5 in HCC. Single-cell and bulk RNA sequencing was used to further investigate the underlying mechanisms involved. RESULTS: This study revealed that ANXA5 is highly expressed in patients with HCC and correlates with poor prognosis. Assays for migration, invasion, and proliferation based on ANXA5 gene knockout and overexpression systems in human HCC cell lines have demonstrated that ANXA5 enhances HCC malignancy in vitro and in vivo. Tube formation assays of HUVECs indicated that ANXA5 facilitates angiogenesis and recruits endothelial cells to HCC cells. Single-cell and bulk RNA sequencing data analysis further confirmed that ANXA5 expression in HCC is associated with hepatocyte metabolism, immune response activation, and various oncogenic signaling pathways. CONCLUSIONS: This study revealed a meaningful association between elevated ANXA5 expression in tumor tissues and an unfavorable prognosis in patients with HCC. In addition, ANXA5 promotes HCC malignancy by promoting invasion and angiogenesis. Thus, ANXA5 has emerged as a promising therapeutic target for HCC and has the potential to improve patient outcomes.

Use of anticoagulants to improve pregnancy outcomes in couples positive for M2 haplotype: A systematic review.

BACKGROUND: Placental mediated pregnancy complications (PMPC) are common, often recurring, and pose a significant health risk to mother and fetus. Evidence suggests that the hypercoagulable state associated with many PMPC, could reflect reduced expression of Annexin 5 (ANXA5), a naturally occurring anticoagulant protein in placental tissue. The ANXA5 M2 haplotype is a genetic variant, which results in reduced expression of ANXA5 protein. M2 haplotype carrier couples may therefore be at increased risk of PMPC. Evidence regarding the effectiveness of anticoagulation to prevent PMPC is inconsistent. Furthermore, studies have not selected or stratified for M2 haplotype carriers, in whom there is a predisposition to hypercoagulability, to assess the effectiveness of anticoagulation, which may vary from those without the M2 haplotype. OBJECTIVES AND RATIONALE: The aim of this study was to systematically review the current evidence to assess whether anticoagulant treatment improves pregnancy outcomes in couples positive for M2 haplotype. SEARCH METHODS: The review was registered on PROSPERO (CRD42022343943). A comprehensive literature search was performed using MEDLINE, Embase and Cochrane collaboration databases from inception to January 2023. Two reviewers assessed the articles for eligibility and extracted the data simultaneously. Primary outcome was successful pregnancy and live birth. Secondary outcomes included PMPC (implantation failure, miscarriage, pre-eclampsia, preterm birth and fetal growth restriction). OUTCOMES: From a pool of 410 references, 10 were selected for full text review, of which three studies (a post hoc analysis of a randomised controlled trial, cohort study and a case report) were included in this review. Included studies comprised of 223 individuals, 129 of whom who received anticoagulation treatment after testing positive for M2 haplotype. The studies collectively showed an improvement in pregnancy outcomes in M2 haplotype positive individuals however, given the heterogeneity of studies, it was not possible to conduct a meta-analysis and draw firm conclusions. WIDER IMPLICATIONS: Current evidence is limited, such that the value of screening couples for the M2 haplotype to select or stratify for treatment with prophylactic anticoagulation remains unknown. Thus, further studies including well designed, large, multi-centre randomised controlled trials are required to assess whether anticoagulation treatment will be effective in improving pregnancy outcomes in M2 haplotype couples.

The macrophage-associated prognostic gene ANXA5 promotes immunotherapy resistance in gastric cancer through angiogenesis.

Gastric cancer (GC) remains a predominant form of malignant tumor globally, necessitating innovative non-surgical therapeutic approaches. This investigation aimed to delineate the expression landscape of macrophage-associated genes in GC and to evaluate their prognostic significance and influence on immunotherapeutic responsiveness. Utilizing the CellMarker2.0 database, we identified 69 immune cell markers with prognostic relevance in GC, including 12 macrophage-specific genes. A Weighted Gene Co-Expression Network Analysis (WGCNA) isolated 3,181 genes correlated with these macrophage markers. The Cancer Genome Atlas (TCGA-STAD) dataset was employed as the training set, while data from the GSE62254 served as the validation cohort. 13 genes were shortlisted through LASSO-Cox regression to formulate a prognostic model. Multivariable Cox regression substantiated that the calculated risk score serves as an imperative independent predictor of overall survival (OS). Distinct macrophage infiltration profiles, pathway associations, treatment susceptibilities, and drug sensitivities were observed between high- and low-risk groups. The preliminary validation of ANXA5 in predicting the survival rates of GC patients at 1 year, 3 years, and 5 years, as well as its expression levels were higher and role in promoting tumor angiogenesis in GC through immunohistochemistry and angiogenesis experiments. In summary, macrophage-related genes were potentially a novel crosstalk mechanism between macrophages and endothelial cells in the tumor microenvironment, and the interplay between inflammation and angiogenesis might have also offered new therapeutic targets, providing a new avenue for personalized treatment interventions.