To explore the potential of carbohydrate sulfotransferase 1 (CHST1) as a novel biomarker in stomach adenocarcinoma (STAD).

We obtained the CHST1 expression value and clinical data of patients with STAD from the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then we explored the expression of CHST1, followed by the expression confirmation of CHST1 protein through immunohistochemistry (IHC). The prognostic value of CHST1 was assessed by Kaplan-Meier (KM), receiver operating characteristic (ROC) curve, Cox regression, and nomogram analyses. The gene set enrichment analysis (GSEA) and immune infiltration analysis were used to explore the CHST1-associated mechanism.

From the TCGA data, CHST1 expression was higher in STAD group than that in normal group ( P<0.05), and IHC further confirmed the upregulation of STAD. It was also found that CHST1 expression was related to the tumor grade (P<0.05). Survival analysis indicated that high expression of CHST1 significantly shortened the overall survival time of patients [hazard ration (HR)=1.64, P<0.001] and could independently predict the prognosis (HR=1.632, P<0.05). The CHST1 showed the favorable performance for predicting the 1-, 3-, and 5-year survival. In addition, age was related to the prognostic value of CHST1 and it significantly affected the survival of patients with age ≤ 60 years old (HR=3.25, P<0.05). The expression of CHST1 and its prognostic value were also confirmed with the data from GEO (all P<0.05). GSEA analysis found that high expression of CHST1 was related to the metastasis pathways such as ECM-receptor interaction, focal adhesion, and cell adhesion molecules (CAMs) (all P<0.05). Due to the close correlation between the immune microenvironment and tumor metastasis, this study further explored the regulation of CHST1 on immune microenvironment in STAD, and it was found that CHST1 was obviously related to the infiltration level of majority of immune cells. Especially, CHST1 high expression inhibited the infiltration of activated CD4⁺ T cells but promoted the infiltration of M0 macrophages and activated mast cells (all P<0.05). Moreover, the expression of CHST1 was significantly correlated with related immune checkpoint genes of these immune cells (all P<0.05).

CHST1 was highly expressed in STAD, which was unfavorable to the patient’s prognosis, and it can be regarded as a promising molecular marker for STAD treatment. In addition, CHST1 might be involved in the invasion and metastasis of STAD by regulating the immune microenvironment.

Stomach carcinoma; Carbohydrate sulfotransferase 1; Prognosis; Pathway