High expression of suppressor of cytokine signaling 1 (SOCS1) associates with favourable responsiveness to neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma

Abstract Background: The responsiveness to preoperative neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) is significantly related to the surgical effect and long-term prognosis of patients. Biomarkers for predicting the effect of preoperative neoadjuvant therapy of ESCC are urgently needed in clinical practice. M2 macrophage in the tumor microenvironment (TME) has been confirmed to have a definite correlation with neoadjuvant therapy. However, the research on the potential functional genes of M2 macrophage has not been carried out. The purpose of this study is to systematically screen the potential functional genes of M2 macrophages and verify the correlation between the expression of screened genes and responsiveness to neoadjuvant therapy in ESCC.Methods: The Cancer Genome Atlas (TCGA) database was used to screen the potential functional genes of M2 macrophages systematically. The correlation between the screened genes and responsiveness to neoadjuvant therapy in ESCC was analyzed in the training set GSE45670 and the validation set GSE104958. The correlation of the screened genes was confirmed in a cohort of 27 patients using immunohistochemistry (IHC).Results: A total of 11 M2 macrophage potential functional genes were screened out. The suppressor of cytokine signaling 1 (SOCS1) and ORAI calcium release-activated calcium modulator 3 (ORAI3) were selected for subsequent verification. The expression of SOCS1 and ORAI3 in 27 cases of ESCC was evaluated by the H-score system. The result showed that the high expression of SOCS1 was significantly correlated with favourable responsiveness to preoperative neoadjuvant therapy (AUC = 0.830, 95% CI: 0.647-1, P = 0.006). No significant correlation was found between the expression of ORAI3 and neoadjuvant therapy in ESCC (AUC=0.688, 95% CI: 0.478-0.899, P=0.117).Conclusion: The high expression of SOCS1 in the local tumor microenvironment is significantly correlated with favourable responsiveness to neoadjuvant therapy in patients with ESCC, which can be used as a biomarker to predict the responsiveness to neoadjuvant therapy, and has certain clinical value.