Department of Oncology, The Affiliated Hospital of Chengde Medical University, Chengde, China.
Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
J Obstet Gynaecol. 2023 Dec;43(1):2213764. doi: 10.1080/01443615.2023.2213764.
To clarify the clinicopathological importance of REG4 mRNA expression, we used GEO, TCGA, xiantao, UALCAN, and Kaplan-Meier plotter for a bioinformatics analysis in breast, cervical, endometrial and ovarian cancers. Compared to normal tissues, REG4 expression was found to be upregulated in breast, cervical, endometrial, and ovarian cancers (p < 0.05). Breast cancer had a higher level of REG4 methylation than normal tissues ( < 0.05), which was negatively correlated with its mRNA expression. REG4 expression was positively correlated with oestrogen and progesterone receptor expression, and aggressiveness of PAM50 classification of breast cancer patients ( < 0.05). Breast infiltrating lobular carcinomas expressed more REG4 than ductal carcinomas ( < 0.05). The REG4-related signal pathways mainly included peptidase, keratinisation, brush border and digestion and so forth in gynecological cancers. Our results indicated that REG4 overexpression was associated with gynecological carcinogenesis and their histogenesis, and may be used as a marker for aggressive behaviour and prognosis of breast or cervical cancer.IMPACT STATEMENT REG4 encodes a secretory c-type lectin and plays an essential role in inflammation, carcinogenesis, apoptotic and radiochemotherapeutic resistance. As a standalone predictor, REG4 expression was positively correlated with progression-free survival. Expression of REG4 mRNA was positively associated with the T stage and adenosquamous cell carcinoma of cervical cancer. The top signal pathways related to REG4 included smell and chemical stimulus, peptidase, intermediate filament, and keratinisation in breast cancer; ligand-receptor interaction, metabolism of hormone, xenobiotic and retinol, peptidase, brush border and digestion in cervical and ovarian cancers; bile secretion, intermediate filament, chemical carcinogenesis, brush border and keratinisation in endometrial cancer. REG4 mRNA expression was positively correlated with DC cell infiltration in breast cancer, positively with Th17 cells, TFH, cytotoxic cells and T cells in cervical and endometrial cancers, and negatively with DC cell infiltration, cytotoxic cells and T cells in ovarian cancer. The top hub genes mainly included small proline rich protein 2B in breast cancer; fibrinogens and apoproteins in cervical, endometrial and ovarian cancers. Our study has showed that REG4 mRNA expression is a potential biomarker or therapeutic target for gynaecologic cancers.
为了阐明 REG4mRNA 表达的临床病理重要性，我们使用 GEO、TCGA、仙桃、UALCAN 和 Kaplan-Meier 绘图器对乳腺癌、宫颈癌、子宫内膜癌和卵巢癌进行了生物信息学分析。与正常组织相比，REG4 在乳腺癌、宫颈癌、子宫内膜癌和卵巢癌中的表达上调（p<0.05）。乳腺癌中 REG4 的甲基化水平高于正常组织（p<0.05），且与 mRNA 表达呈负相关。REG4 的表达与雌激素和孕激素受体的表达以及乳腺癌患者 PAM50 分类的侵袭性呈正相关（p<0.05）。浸润性小叶癌的 REG4 表达高于导管癌（p<0.05）。REG4 相关信号通路主要包括妇科癌症中的肽酶、角化、刷状缘和消化等。我们的研究结果表明，REG4 过表达与妇科癌症的发生和组织发生有关，可能作为乳腺癌或宫颈癌侵袭性行为和预后的标志物。
声明：REG4 编码一种分泌型 C 型凝集素，在炎症、癌变、凋亡和放化疗耐药中发挥重要作用。作为一个独立的预测因子，REG4 的表达与无进展生存期呈正相关。REG4mRNA 的表达与宫颈癌的 T 分期和腺鳞癌呈正相关。与 REG4 相关的主要信号通路包括乳腺癌中的嗅觉和化学刺激、肽酶、中间丝和角化；宫颈癌和卵巢癌中的配体-受体相互作用、激素、外源性和视黄醇代谢、肽酶、刷状缘和消化；子宫内膜癌中的胆汁分泌、中间丝、化学致癌作用、刷状缘和角化。REG4mRNA 表达与乳腺癌中的树突状细胞浸润呈正相关，与宫颈癌和子宫内膜癌中的 Th17 细胞、TFH、细胞毒性细胞和 T 细胞呈正相关，与卵巢癌中的树突状细胞浸润、细胞毒性细胞和 T 细胞呈负相关。主要的枢纽基因主要包括乳腺癌中的小脯氨酸丰富蛋白 2B；宫颈癌、子宫内膜癌和卵巢癌中的纤维蛋白原和载脂蛋白。我们的研究表明，REG4mRNA 表达是妇科癌症的潜在生物标志物或治疗靶点。
