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. 2025 Jul 29;18(1):167.
doi: 10.1186/s13048-025-01758-4.

SLC4A11 is a targetable marker correlated with therapeutic responses in ovarian cancer

Xin Li  1   2 , Jia Yuan  1   2 , Fanchen Wang  1   2 , Bin Guan  1   2 , Wencai Guan  1 , Jimin Shi  1 , Qi Lu  1   2   3 , Jihong Zhang  4 , Guoxiong Xu  5   6
Affiliations

SLC4A11 is a targetable marker correlated with therapeutic responses in ovarian cancer

Xin Li et al. J Ovarian Res. .

Abstract

Background: Solute carrier family 4 member 11 (SLC4A11) is involved in borate homeostasis, metabolism reprogramming, cell growth, and cell adhesion. However, the biological function of SLC4A11 in ovarian cancer (OC) is still unclear. This study explores the anti-tumor and biological activities of SLC4A11 in OC.

Methods: The expression and function of SLC4A11 were evaluated in human OC cells and xenograft mice. SLC4A11 expression was evaluated using data from the TCGA-OV, GTEx, and GEO datasets. The genetic status of SLC4A11 was analyzed by the cBioPortal database. The data of expressional abundance, immunochemistry, and immunofluorescence were analyzed through the HPA database. The correlation between SLC4A11 and immune responses was analyzed with the CIBERSORT database, whereas therapeutic responses were analyzed with the CellMiner database.

Results: SLC4A11 was found to be highly expressed in OC tissues/cells and had a relationship with an unfavorable prognosis in patients with OC. The overexpressed SLC4A11 promoted OC cell proliferation, migration, and invasion. Reducing SLC4A11 caused the cell cycle arrest at the G0/G1 phase and triggered apoptosis. The in vivo study with a xenographic model revealed that the knockdown of SLC4A11 suppressed tumor growth. Subsequent bioinformatics analyses revealed that SLC4A11 expression was associated with immune responses and therapeutic drug sensitivity.

Conclusions: These findings have illustrated the oncogenic role of SLC4A11 in OC. SLC4A11 is overexpressed and is correlated with poor prognosis in OC. SLC4A11 may be a targetable biomarker and has a potential value of application in treating patients with OC.

Keywords: Anti-cancer therapy; Cell death; Cellular processes; Immune response; Ovary; Tumorigenesis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The ethical approval of the study for human subjects was approved by the Ethics Committee of Jinshan Hospital of Fudan University (approval no. JIEC-2022-S10). The written informed consent was obtained from the patients. Animal studies were approved by the Laboratory Animal Welfare and Ethics Committee of the Shanghai Public Health Clinical Center of Fudan University (approval no. 2022-A041-01). Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Characteristics of SLC4A11 expression in human cancer. (A) Expressional alterations of SLC4A11 in 33 types of cancer from the GEPIA database. SLC4A11 was upregulated in 9 types of cancer, while downregulated in 5 types of cancer. Cancers in red represent the upregulation of SLC4A11, whereas cancers in green represent the downregulation of SLC4A11. (B) The rank of the levels of differentially expressed SLC4A11 in 30 cancers from the HPA database. (C) Overexpression of SLC4A11 was verified in ovarian cancer (OC) tissues. Representative immunohistochemistry (IHC) images of SLC4A11 in non-tumor and OC tissues. Original magnification, x400; Scale bar, 50 μm. (D) IHC scores of SLC4A11 staining. (E) SLC4A11 mRNA expression in normal ovarian tissues (Normal) and OC tissues (Tumor). SLC4A11 was upregulated in 379 OC tissues from the TCGA-OV database compared with 88 normal ovarian tissues from the GTEx database. (F) SLC4A11 mRNA expression was upregulated in OC tissues compared with normal ovarian tissues based on data from five GEO datasets (GSE14407, GSE18521, GSE52460, GSE40595, and GSE38666). Data was presented as mean ± SD. P-values were calculated by a two-sided unpaired Student’s t-test. **p < 0.01; ***p < 0.001; ****p < 0.0001
Fig. 2
Fig. 2
Association of SLC4A11 with the prognosis of ovarian cancer patients. (A) Genomic mutant of SLC4A11. Data were downloaded from the cBioPortal database. (B) Correlation of the overall survival between the genomic-altered SLC4A11 and genomic-unaltered SLC4A11 groups. (C) Association of overall survival with SLC4A11 based on the clinical information and expression matrix from the TCGA-OV database using the ‘survival’ R package. (D, E) Association of progression-free survival with SLC4A11 based on the data from the Kaplan-Meier Plotter database
Fig. 3
Fig. 3
Correlated genes and functional enrichments of SLC4A11. (A) Biological Process (BP) enrichment of SLC4A11 based on a total of 439 correlated genes using the DAVID database. (B, C) Data extracted from the TCGA-OV database were divided into SLC4A11-high and -low groups. The GSEA enrichment was performed in SLC4A11-high (B) and -low (C) groups, respectively, using the ‘org.Hs.eg.db’, ‘clusterProfiler’, and ‘enrichplot’ R packages. (D) Top 30 positively correlated genes of SLC4A11 from the TCGA-OV database.|Cor| >0.3, P-value < 0.05. (E) Top 30 negatively correlated genes of SLC4A11 from the TCGA-OV database.|Cor| >0.3, P-value < 0.05
Fig. 4
Fig. 4
Detection of SLC4A11 expression and apoptotic cells. (A) Detection of SLC4A11 mRNA expression in a non-tumorous ovarian surface epithelial cell line (IOSE-80) and 3 ovarian cancer cell lines (OVCAR-3, A2780, and SK-OV-3) by qRT-PCR. n = 3. (B) Detection of SLC4A11 protein in IOSE-80, OVCAR-3, A2780, and SK-OV-3 by Western blot. Representative images are shown. (C) Measurement of the value of the bands in (B) by ImageJ and plotted by Prism 8.0 software. (n = 3). Data were presented as mean ± SD (A, C). P-values were calculated by one-way ANOVA followed by Tukey’s multiple comparisons test. (D) Detection of apoptotic cells by flow cytometry in OVCAR-3 and A2780 cells after either infection with sh-SLC4A11 lentivirus or transfection with oe-SLC4A11 plasmid. Knockdown of SLC4A11 increased the apoptotic rate. (E) Detection of apoptotic cells by flow cytometry in OVCAR-3 and A2780 cells after transfection with oe-SLC4A11 plasmid. Overexpression of SLC4A11 decreased the apoptotic rate. Data was presented as mean ± SD (n = 3). The unpaired Student’s t-test was used for a two-group comparison. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001
Fig. 5
Fig. 5
Effect of SLC4A11 on ovarian cancer cell proliferation. (A) Measurement of cell viability in OVCAR-3 and A2780 cells after sh-SLC4A11 infection. (B) Measurement of cell viability in OVCAR-3 and A2780 cells after oe-SLC4A11 transfection. (C) Detection of cell proliferation by the EdU assay in sh-SLC4A11-infected OVCAR-3 and A2780 OC cells. Original magnification, x40; Scale bar, 100 µM. (D) Statistical analysis of (C) using ImageJ software. (E) Detection of cell proliferation by the EdU assay in oe-SLC4A11-transfected OVCAR-3 and A2780 cells. Original magnification, x40; Scale bar, 100 µM. (F) Statistical analysis of (E) using ImageJ software. Data was presented as mean ± SD (n = 3). The unpaired Student’s t-test was used for a two-group comparison. sh-NC, negative control shRNA; sh-SLC4A11, SLC4A11-shRNA; oe-SLC4A11, SLC4A11-overexpressing plasmid; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001
Fig. 6
Fig. 6
Measurement of the cell cycle in OVCAR-3 and A2780 ovarian cancer (OC) cells. (A) Knockdown of SLC4A11 arrested the cell cycle at the G0/G1 phase in OC cells. (B) Overexpression of SLC4A11 shortened the G0/G1 phase of OC cells. (C) Detection of cyclin D1 protein by Western blot in sh-SLC4A11-infected and oe-SLC4A11-transfected OC cells. (D) Detection of cyclin E1 protein by Western blot in sh-SLC4A11-infected and oe-SLC4A11-transfected OC cells. (E) The semi-quantitative analysis of bands in (C) and (D) was done by ImageJ software and plotted by the Prism 8.0 software. Data was presented as mean ± SD (n = 3). The unpaired Student’s t-test was used for a two-group comparison. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001
Fig. 7
Fig. 7
Effect of SLC4A11 on ovarian cancer (OC) cell migration and invasion and tumor formation. A2780 and OVCAR-3 cells were either infected with shRNA (sh-SLC4A11) or transfected with an overexpressing plasmid (oe-SLC4A11). (A) OC cell migration after SCL4A11 knockdown. (B) OC cell invasion after SCL4A11 knockdown. (C) OC cell migration after SLC4A11 overexpression. (D) OC cell invasion after SLC4A11 overexpression. The right bar plot is the statistical quantification of the migration and invasion. Data were presented as mean ± SD (n = 3). The unpaired Student’s t-test was used for a two-group comparison. (E) Effect of SLC4A11 on tumor formation. The xenograft mouse model was generated by subcutaneous injection with sh-SLC4A11-infected A2780 cells. Tumors were isolated and photographed after the animals were sacrificed. (F) Measurement of tumor volume and tumor weight in sh-NC and sh-SLC4A11 groups. (G) Detection of SLC4A11 mRNA expression in the tumor of the xenograft mouse model by qRT-PCR. (H) Detection of SLC4A11 and Ki-67 proteins in the tumor samples of the xenograft mice by IHC staining and images were photographed. Original magnification, x200; Scale bar, 50 µM. (I) Statistical analysis of (H) using ImageJ software. The unpaired Student’s t-test was used for a two-group comparison. Data was presented as mean ± SD (n = 5). sh-NC, negative control shRNA; sh-SLC4A11, SLC4A11-shRNA; oe-SLC4A11, SLC4A11-overexpressing plasmid; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001
Fig. 8
Fig. 8
Correlation of SLC4A11 with tumor-infiltrating immune cells and immune responses. (A) Different enrichment scores of immune cells between SLC4A11-high and -low groups. Data were extracted from the TCGA-OV database. (B) Correlation of the expression of SLC4A11 with immune cells using Pearson Correlation Analysis. Data were from the TCGA-OV database. (C) Difference of TIDE, Exclusion, and dysfunction scores between SLC4A11-high and -low groups based on the TCGA-OV database using the ‘limma’ and ‘ggpubr’ R packages. TIDE, Tumor Immune Dysfunction and Exclusion; *p < 0.05; **p < 0.01; ***p < 0.001
Fig. 9
Fig. 9
Correlation of SLC4A11 expression with therapeutic drugs. The association between the half inhibitory concentration (IC50) of therapeutic drugs and the expression level of SLC4A11 in ovarian cancer cells was analyzed based on the CellMiner database. p < 0.05 was considered significant. Pearson Correlation Analysis was applied for the analysis using the ‘impute’, ‘limma’, ‘ggplot2’, and ‘ggpubr’ R packages
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