Gastric cancer remains one of the most lethal and prevalent malignancies, particularly in China. The majority of patients are diagnosed with gastric cancer at the late stages of the disease. Besides, the high relapse rate also contributes to the high mortality. Therefore, there exists an imperative need for the development of gastric cancer diagnostic techniques as well as novel indicators for gastric cancer metastasis. Exosomes, secreted by a variety of cell types, play critical roles in intercellular communication, which emerge as promising diagnostic biomarkers for gastric cancer. In this study, we present for the first time, at least to the best of our knowledge, the small RNA sequencing spectra of exosomes derived from the gastric cancer patient plasma using next-generation sequencing, focusing on the exploration of metastasis-related biomarkers. The exosomes enriched from patient plasma samples were well characterized by western blotting, transmission electron microscopy and nanoparticle-tracking analysis. In the following bioinformatic analysis of exosomal miRNAs, three candidates were proposed as the biomarkers for metastasis of gastric cancer, namely miR-10b-5p, miR-101-3p and miR-143-5p, for gastric cancer with lymph node metastasis, gastric cancer with ovarian metastasis and gastric cancer with liver metastasis, respectively. RT–qPCR was performed to test the accuracy of these candidates for validation. In conclusion, we successfully isolated and purified exosomes from plasma of patients with gastric cancer and identified several potential exosomal miRNA markers to distinguish gastric cancer patients with various kinds of metastasis.
9 October 2019 in Journal of Cancer Research and Clinical Oncology
Gastric cancer (GC) is one of the most common types of human cancers. However, the mechanisms underlying GC remained largely unclear. To determine whether the differentially expressed mRNAs, lncRNAs and circRNAs in GC, we screened conducted SBC-ceRNA microarray analysis in 3 pairs of GC and normal tissues. Furthermore, differentially expressed mRNAs mediated protein protein interaction (PPI) networks, lncRNAs mediated cis-regulatory network, and circRNA mediated ceRNA network were for the first time constructed to reveal their potential functions and mechanisms in GC. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was conducted to validate the microarray analysis. A total of 922 mRNAs, 2112 lncRNAs and 2896 circRNAs were observed to be dysregulated in GC samples. Bioinformatics analysis showed these differentially expressed genes (DEGs) were significantly associated with regulating branched - chain amino acid catabolic process, Glycolysis/Gluconeogenesis and ARF protein signal transduction. Moreover, we found the dysregulation of key mRNAs and lncRNAs were associated with the overall survival time in GC patients. We believe this study provides useful information for understanding the mechanism underlying GC progression and exploring potential therapeutic and prognostic targets for GC.
20 August 2022 in Journal of Cancer Research and Clinical Oncology
Gastric cancer remains one of the most prevalent tumors worldwide and peritoneal metastasis is responsible for approximately 60% of death in advanced gastric cancer patients. However, the underlying mechanism of peritoneal metastasis is poorly understood. We have established organoids derived from malignant ascites (MA) of gastric cancer patients and noticed that MA supernatant could strongly increase the colony formation of organoids. Thus, we realized the interaction between exfoliated cancer cells (ECCs) and liquid tumor microenvironment contributes to peritoneal metastasis. Further, we designed a medium component control test which proved that exosomes derived from MA could not enhance the growth of organoids. Using Immunofluorescence and confocal imaging as well as dual-luciferase reporter assay, our data showed WNT signaling pathway was upregulated by high concentrations of WNT ligands (wnt3a and wnt5a), which was verified by ELISA. Besides, suppressing WNT signaling pathway diminished the growth promoting function of MA supernatant. This result implicated WNT signaling pathway as a potential therapeutic target for peritoneal metastasis of gastric cancer.
The role of SLC35A2 in breast cancer remains poorly understood, with limited available information on its significance. This study aimed to investigate the expression of SLC35A2 and clinicopathological variables in breast cancer patients. Immunohistochemical analysis of SLC35A2 protein was conductedon 40 adjacent non-neoplastic tissues and 320 breast cancer tissues. The study also assesed the association between SLC35A2 expression and breast cancer clinicopathological features of breast cancer, as well as its impact on overall survival. In comparison to adjacent non-neoplastic tissues, a significantly higher expression of SLC35A2 was observed in breast cancer tissues (P = 0.020), and this expression was found to be independently correlated with HER2 positivity (P = 0.001). Survival analysis indicated that patients with low SLC35A2 expression had a more favorable prognosis in HER2-positive subtype breast cancer (P = 0.017). These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.