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Background Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. Methods GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. Results Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Conclusion These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy.

Introduction:G-protein-coupled receptor 176 (GPR176) is a member of the G-protein coupled receptor (GPCR) 1 family and produces a 515 amino acid glycosylated protein. Materials and Methods: In the present study, GPR176 expression was detected using immunohistochemistry (IHC) and compared with clinicopathological characteristics of ovarian cancer using bioinformatics analysis. GPR176-related genes and pathways were analyzed using bioinformatics analysis. In addition, the effects of GPR176 on the phenotypes of ovarian cancer cells were investigated. Results:GPR176 mRNA expression positively correlated with older age, clinicopathological staging, tumor residual status, and unfavorable survival of ovarian cancer (p < 0.05) but negatively with purity loss, infiltration of B cells, and CD8+ T cells (p < 0.05). Gene Set Enrichment Analysis (GSEA) showed that differential expression of the GPR176 gene was involved in focal adhesion, ECM-receptor interaction, ribosome, oxidative phosphorylation, actin skeleton, cytokine-cytokine receptor interaction, gap junction, and cell adhesion molecules (p < 0.05). STRING and Cytoscape were used to determine the top 10 nodes (FN1, COL1A1, MMP2, COL1A2, COL3A1, THBS1, ACAN, DCN, COL5A1, LUM) which were downregulated in ovarian cancer (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that GPR176-related genes were categorized into the AGE-RAGE signaling pathway in diabetic complication, ECM receptor interaction, protein digestion and absorption, ECM structural constituent and organization, and collagen trimer (p < 0.05). GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and underexpression of gasdermin D, caspase 1, and E-cadherin. These results indicated that GPR176 might be involved in the progression of ovarian cancer by deteriorating aggressive phenotypes. Conclusion:GPR176 could potentially be used as a biomarker to indicate the aggressive behavior and poor prognosis of ovarian cancer and a target of genetic therapy.

A 38-year-old woman underwent a hysterectomy for a uterine tumor. A giant circumscribed nodule with a diameter of 20 cm at its widest point was found within the myometrium of the uterine corpus without hemorrhage or necrosis. More than 10 specimens were pathologically examined. Eleven years after hysterectomy, she developed fi ve tumors (the largest diameter = 2 cm) in the right lung and retroperitoneal tumor (the largest diameter = 9.5 cm). Microscopic examination indicated uterine, retroperitoneal and pulmonary foci, which were characterized by a benign appearance, including nodular smoothmuscle proliferation. The smooth muscle cells had an oval shape with relatively clear cytoplasm and a few irregular nuclei. In each specimen, spindle-shaped cells showed an interlacing bundle pattern with intermediated cellularity. The mitotic index was very low and no nuclear atypia was observed (Fig.1). Even though the serial pathological examination did not indicate any malignant potential, we diagnosed this case as benign metastasizing leiomyoma (BML).In the present case, pulmonary (BML-P) and retroperitoneal (BML-R) metastases and primary foci (BML-U) of uterine leiomyoma were examined with one case of non-metastasizing leimyoma of the uterus (NML) and one case of leiomyosarcoma (LS) as control. All tissues were fi xed in 4% neutralized formaldehyde, embedded in paraffi n and cut into 4 m sections. These sections were stained by H&E and then immuhistochemically stained using