Studies have shown that LGALS1 expression is elevated in cancer tissues such as gastric cancer, ovarian cancer, and neuroblastoma, and is associated with poor prognosis in gastric cancer, ovarian cancer, and neuroblastoma patients [11, 21–23]. However, the expression and potential clinical value of LGALS1 in esophageal cancer tissues have not been reported in the literature. We analyzed the Oncomine, Timer, and TCGA databases and found that LGALS1 expression was elevated in ESCA tissues, which was consistent with the expression in gastric, ovarian, and neuroblastoma. Moreover, the expression level of LGALS1 was also related to age, race, weight, smoking history, cancer stage, tumor grade, histological subtype and lymph node metastasis in ESCA patients. In addition, ROC analysis found that LGALS1 had an AUC of 0.8511 in ESCA and was statistically significant. These results indicate that LGALS1 is involved in ESCA progress and is expected to become a potential new target for diagnosis and treatment of ESCA.
Currently, LGALS1 acts as an oncogene in tumors to promote cancer progression. For example, Galectin-1 is upregulated in hepatocellular carcinoma cells and can regulate hepatocellular carcinoma cell adhesion, polarization, and tumor growth in vivo . Galectin-1 overexpression can activate FAK/PI3K/AKT signaling pathway to induce the resistance of EMT and sorafenib in liver cancer . Galectin-1 can also cause β-catenin nuclear translocation in liver cancer, as well as increased TCF4/LEF1 transcriptional activity, cyclin D1 and proto-oncogene expression . TLR (Toll-like receptor) can mediate PI3K activation regulation through Galectin-1 production, and then participate in regulating ovarian cancer cell invasion and metastasis . Galectin-1 overexpression promotes the proliferation and metastasis of pancreatic cancer cells, and can promote the expression of fibronectin, collagen type I, α-SMA, MMP-2 and TIMP-1 through the TGF-β1/Smad signaling pathway . In gastric cancer, overexpression of Galectin-1 can enhance TGF-β signaling through positive feedback, reduce cancer cell apoptosis, and promote cancer cell migration and invasion . Most cytokines are synthesized by immune cells and secrete a small class of proteins with a wide range of biological activities. Interfering with LGALS1 expression can down-regulate M2 macrophages and myeloid-derived suppressor cells (MDSCs), and suppress immunosuppressive cytokines, and immunosuppressive microenvironment of glioma . Galectin-1 can inhibit the viability, proliferation, and Th1 cytokine production of non-malignant T cells in patients with leukemia skin T-cell lymphoma . These results indicate that LGALS1 can participate in tumor progression through PI3K/AKT signaling pathway, TGF-β signaling pathway, and regulation of cytokines secreted by immune cells. We performed GO, KEGG, and GSEA analysis of mRNA expression data in the TCGA database. GO shows that LGALS1 co-expressed genes are mainly involved in endothelial cell differentiation, transforming growth factor receptor signaling pathway, epithelial cell proliferation, and ECM receptor interaction. LGALS1 may be involved in the progression of ESCA including leukocyte migration, transcriptional disorders during cancer, PI3K/AKT signaling pathway, ECM receptor interaction, cancer pathway, TGF BETA signaling pathway, cytokine and cytokine interaction, etc. Combined with the report, LGALS1 can participate in cancer progression through the PI3K/AKT signaling pathway, TGF-β signaling pathway, and regulate the secretion of cytokines by immune cells. We believe that LGALS1 can participate in the development of ESCA through PI3K/AKT signaling pathway, TGF BETA signaling pathway, cancer pathway, cytokine and cytokine interaction.
The hub genes in the PPI network are COL1A1, FN1, COL1A2, COL3A1, COL5A1, COL5A2, COL4A2, COL18A1, COL6A2, and COL6A1. The Hub gene has extremely important clinical significance in the progress of cancer. COL1A1 and fibronectin 1 (FN1) are highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. Both COL1A1 and FN1 can promote ESCC cell proliferation and invasion [32, 33]. COL1A2 is significantly down-regulated in colorectal cancer (CRC) tissues, and COL1A2 mRNA expression levels are related to tumor differentiation, invasion, and lymph node metastasis in CRC patients. COL1A2 overexpression inhibited CRC cell line proliferation, migration, and invasion . COL3A1 expression is elevated in CRC tissues and cells. The increase of COL3A1 expression is related to T stage, Dukes stage, grade, recurrence, etc. in patients with CRC. Patients with elevated COL3A1 expression had poorer overall and disease-free survival. COL3A1 in plasma has an AUC of 0.92 in CRC. Silencing COL3A1 expression can inhibit CRC cell proliferation . Interfering the expression of COL5A1 in metastatic lung adenocarcinoma cells inhibits cell growth and invasion, and induces apoptosis . Increased IDO1 expression promotes gastric cancer cell migration. Interfering with IDO1 expression in GC cells reduced LOXL2, COL6A1, COL6A2, and COL12A1 mRNA and protein expressions . These results indicate that these hub genes are related to tumorigenesis and development.
We analyzed the correlation between LGALS1 and hub genes in the GEPIA database. In addition, we found in the TCGA database that COL1A1, FN1, COL1A2, COL3A1, COL5A1, COL5A2, COL4A2, COL18A1, and COL6A1 are elevated in ESCA tissue and have diagnostic significance. LGALS1 is involved in the progression of ESCA and is a new diagnostic target for ESCA patients. In other tumors, studies have reported that Hub genes and PI3K/AKT signaling pathways, TGF-β signaling pathways, and cytokine regulatory mechanisms have extremely important roles. The regulatory relationships between LGALS1 and Hub genes, PI3K/AKT signaling pathway, TGF-β signaling pathway, and cytokines in ESCA are unclear, and further research and verification are needed.
In summary, we show that the increased expression of LGALS1 is related to the clinicopathological characteristics of ESCA patients and can be used as a potential target for ESCA diagnosis. Moreover, LGALS1 may promote the development of ESCA through PI3K/AKT signaling pathway, TGF BETA signaling pathway, cancer pathway, cytokine and cytokine interaction.