At present, increasing evidence demonstrates that the occurrence and development of BC are based on the accumulation of gene alterations to make qualitative changes, so exploring biomarkers is particularly important in the occurrence, development, diagnosis, treatment and prognosis evaluation of BC. Multiple studies have found that SOCS3 provides additional direction in prognostic management and treatment strategy in many human cancers, such as breast cancer, acute myeloid leukemia, ovarian cancer, and so on[20–22]. Besides, SOCS3 has also been found to be involved in the infiltration of various immune cells including macrophages and neutrophils, as well as participate in various biological functions through the JAK-STAT pathway [23, 24].
In this study, we investigated whether SOCS3 status has a potentially prognostic effect and its potential biological function in BC. Our study found that SOCS3 was significantly lower in BC tumor tissues compared with normal tissues, both in transcription and protein levels. And SOCS3 was a possible tumor suppressor gene, which was similar to the results of previous studies [25]. In addition, our study also found that as the stage and grade increased, the expression of SOCS3 in immunohistochemistry decreased, indicating that patients with higher malignancy levels had lower SOCS3 expression. Through prognostic analysis, we found that the SOCS3 status was related to the prognosis of NIMBC and may be a potential prognostic factor for NIMBC, but this result requires a larger number of samples and more comprehensive clinical factors to verify. Through enrichment analysis between SOCS3 high and low expression groups, SOCS3 had also been found to be involved in the extracellular matrix and cell adhesion process, which suggested that SOCS3 might be involved in cell-to-cell and cell-to-extrinsic interactions, thereby affecting cell behaviors such as cell migration and growth. Subsequently, we overexpressed SOCS3 in the bladder cancer cell line and found that ectopic expression of SOCS3 reduced the cell proliferation and migration ability of the tumor cell line, which also suggested that SOCS3 is a tumor suppressor gene in BC.
SOCS3 is one of the relatively well-understood members of the SOCS family, but less research has been done on BC. All members of the SOCS family have similar protein structures, including a variable N- terminal domain with varying amino acid lengths, a central SH domain, and a conserved C- terminal region with 40 amino acids (SOCS box) which is thought to directly counteract the activation of STATs and generate a classic feedback loop[26]. SOCS protein, as a negative regulator of the signal transduction pathway, has become a new target for the treatment of various tumors. Previous studies have found that SOCS3 is an important negative regulator of JAK/STAT and is involved in the malignant transformation of various tumors, including breast cancer, colorectal cancer, liver cancer, and gastric cancer. In addition, a variety of molecules, such as microRNAs and lncRNAs, can affect tumor development processes by regulating the expression of SOCS3, including tumor cell proliferation, cell cycle, apoptosis, invasion, metastasis, drug sensitivity and radiosensitivity[27, 28]. Our study complements the prognostic significance and related biological functions of SOCS3 in BC and found that SOCS3 is a potential prognostic factor in BC, and its ectopic expression can inhibit tumor proliferation and migration, demonstrating the negative regulatory role of SOCS3 in BC.
Our research explored the prognostic effect of SOCS3 in BC by immunohistochemistry, used data from public databases to verify, and the biological function of SOCS3 in BC was further explored. However, our study subject was the prognostic role of SOCS3 status in a small number of BC patients, so it is not known for possible underlying mechanisms and whether our results were applicable to a large population, and further studies would be needed to investigate. Our findings raise the possibility that SOCS3 is a potential prognostic factor for NMIBC, but larger studies with longer follow-up are necessary to further investigate the prognostic effect of SOCS3 in BC. Also, we found that SOCS3 participated in a variety of biological functions in BC, especially in cell-to-cell and cell-to-extrinsic interactions, and carried out a series of functional experiments to verify, but further functional experiments in vivo and in vitro are still needed to verify the role of SOCS in BC and explore its molecular mechanism.