ELF3 emerges as a novel prognostic indicator implicated in gastric cancer progression and correlated with unfavorable clinical outcomes

Figure 1 Pan-cancer and multi-cohort analysis verifies E74-like ETS transcription factor 3 upregulation in stomach adenocarcinoma. A: E74-like ETS transcription factor 3 (ELF3) mRNA level was upregulated in various types of malignancies from the TIMER database, including stomach adenocarcinoma (STAD); B: ELF3 mRNA level was markedly increased in STAD tissues from the UALCAN database; C: ELF3 protein expression level in STAD. Immunohistochemistry images of ELF3 in STAD and normal gastric tissues in the HPA database. ^aP < 0.05, ^bP < 0.01, and ^cP < 0.001. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.

Figure 2 The mRNA expression of E74-like ETS transcription factor 3 was significantly higher in stomach adenocarcinoma samples. A-H: Compared to normal samples as analyzed in relation to patients’ race, gender, age, cancer stage, tumor grade, Helicobacter pylori infection status, TP53 mutation status, and nodal metastasis status. Multiple group comparisons were performed with ANOVA followed by the Bonferroni post hoc test, detailed statistical analysis is provided in Supplementary Table 1. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.

Figure 3 Prognostic value of E74-like ETS transcription factor 3 in stomach adenocarcinoma. A and B: High E74-like ETS transcription factor 3 expression was related to shorter disease-free survival and overall survival in stomach adenocarcinoma patients from GEPIA and Kaplan-Meier plotter databases; C-J: High E74-like ETS transcription factor 3 expression was related to worse overall survival in different subgroups, including stage I, stage III, stage T3, stage N2, female, intestinal type, poorly differentiated and moderately differentiated. ELF3: E74-like ETS transcription factor 3; HR: Hazard ratio.

Figure 4 Correlation between E74-like ETS transcription factor 3 expression and prognosis of stomach adenocarcinoma patients from the study population cohort. A: Immunohistochemistry images of E74-like ETS transcription factor 3 (ELF3) in stomach adenocarcinoma (STAD) and matched normal tissues; B: Expression was verified using the GEPIA database, and the results showed that ELF3 was overexpressed in STAD tissues; C and D: The expression of ELF3 was positively correlated with Ki-67 expression, and negatively correlated with E-cadherin expression; E: High ELF3 expression in STAD patients was related to worse survival. ^aP < 0.05. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma; OS: Overall survival.

Figure 5 E74-like ETS transcription factor 3 expression in the tumor microenvironment of stomach adenocarcinoma at the single-cell level. A: Heatmap of E74-like ETS transcription factor 3 expression value in different cell types from two datasets in the TISCH database; B-I: The single-cell cluster maps of E74-like ETS transcription factor 3 distribution in stomach adenocarcinoma_GSE134520 and stomach adenocarcinoma_GSE167297 datasets. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.

Figure 6 Correlation between E74-like ETS transcription factor 3 expression and immune infiltrates in stomach adenocarcinoma. A: Correlation between E74-like ETS transcription factor 3 (ELF3) and abundance of 6 immune cells in TIMER; B: Heatmap of the relationship between ELF3 and abundance of 28 tumor-infiltrating lymphocytes in different tumors using the TISIDB database; C-N: ELF3 was negatively related to the abundance of activated B cells, neonatal B cells, macrophage, mast, natural killer, natural killer T, CD4 T cells, CD8 T cells, follicular helper T cells, T helper 1, T helper 2, and Tregs in stomach adenocarcinoma using the TISIDB database. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.

Figure 7 Correlation between E74-like ETS transcription factor 3 expression and immunomodulators in stomach adenocarcinoma. A: Heatmap of correlations between E74-like ETS transcription factor 3 (ELF3) and immune inhibitors across different cancers from TISIDB; B: Relationships between ELF3 and immune inhibitors in stomach adenocarcinoma, the results show a negative correlation; C: Heatmap of correlations between ELF3 and immune stimulants across different cancers from TISIDB; D: Relationships between ELF3 and immune stimulants in stomach adenocarcinoma, the results show a negative correlation. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.

Figure 8 Correlation between E74-like ETS transcription factor 3 expression and chemokines in stomach adenocarcinoma. A: Heatmap of correlations between E74-like ETS transcription factor 3 (ELF3) and chemokines in different cancers from TISIDB database; B: Correlations between ELF3 expression and chemokines in stomach adenocarcinoma from TISIDB database; C: Heatmap of correlations between ELF3 and receptors in different cancers from TISIDB database; D: Relationships between ELF3 and receptors in stomach adenocarcinoma from TISIDB database. ELF3: E74-like ETS transcription factor 3; STAD: Stomach adenocarcinoma.