SLC7A2 serves as a potential biomarker and therapeutic target for ovarian cancer

Sun, Tianshui; Bi, Fangfang; Liu, Zhuonan; Yang, Qing

doi:10.18632/aging.103433

Cited by 23 publications

(16 citation statements)

References 41 publications

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“…At present, studies have found that SLC7A2 plays critical roles in ovarian cancer and breast cancer 38 , 39 . Loss of SLC7A2 augments inflammation-associated colon tumorigenesis 21 .…”

Section: Discussionmentioning

confidence: 96%

SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

Xia

Zhou

et al. 2021

Cell Death Dis

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The main reason for poor prognosis in hepatocellular carcinoma (HCC) patients is high metastasis and recurrence. Cancer progression depends on a tumor-supportive microenvironment. Therefore, illustrating the mechanisms of tumor immunity in underlying HCC metastasis is essential. Here, we report a novel role of solute carrier family 7 member 2 (SLC7A2), a member of the solute carrier family, in HCC metastasis. The reduction of SLC7A2 was an independent and significant risk factor for the survival of HCC patients. Upregulation of SLC7A2 decreased HCC invasion and metastasis, whereas downregulation of SLC7A2 promoted HCC invasion and metastasis. We further found that deficient SLC7A2 medicated the upregulation of CXCL1 through PI3K/Akt/NF-kκB pathway to recruit myeloid-derived suppressor cells (MDSCs), exerting tumor immunosuppressive effect. Moreover, we found that G9a-mediated di-methylation of H3K9 (H3K9me2) silenced the expression of SLC7A2 to suppress HCC metastasis and immune escape. In conclusion, G9a-mediated silencing of SLC7A2 exerts unexpected functions in cancer metastasis by fostering a tumor-supportive microenvironment through CXCL1 secretion and MDSCs recruitment. Thus, SLC7A2 may provide new mechanistic insight into the cancer-promoting property of MDSCs.

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“…At present, studies have found that SLC7A2 plays critical roles in ovarian cancer and breast cancer 38 , 39 . Loss of SLC7A2 augments inflammation-associated colon tumorigenesis 21 .…”

Section: Discussionmentioning

confidence: 96%

SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

Xia

Zhou

et al. 2021

Cell Death Dis

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“…SLC7A2 is a novel biomarker for the diagnosis and treatment of OC. 24 PRDX-1 expression in tumor tissue can be a biomarker for the prognosis of patients with OC. 25 Increased expression of TET3 predicts an unfavorable prognosis for OC patients.…”

Section: Discussionmentioning

confidence: 99%

The Immune-Related Gene ELF3 is a Novel Biomarker for the Prognosis of Ovarian Cancer

Xu¹,

Wang²,

Li³

et al. 2021

IJGM

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Background Ovarian cancer (OC) is a fatal gynaecological malignancy. The study aimed to conduct a comprehensive study to determine the role of ELF3 in OC through bioinformatic analysis. Methods Kruskal–Wallis test, Wilcoxon sign-rank test, and logistic regression were used to evaluate the relationship between clinical characteristics and ELF3 expression. Kaplan–Meier method and Cox regression analysis were used to evaluate the prognostic factors. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to evaluate the significant involvement of ELF3 in function. Results High ELF3 expression in OC was associated with age (P< 0.001). High ELF3 expression predicted a poorer overall survival (OS) (HR: 1.37; 95% CI: 1.05–1.78; P=0.019) and disease specific survival (DSS) (HR: 1.43; 95% CI: 1.08–1.89; P=0.013). And ELF3 expression (HR: 1.779; 95% CI: 1.281–2.472; P<0.001) was independently correlated with OS in OC patients. GSEA demonstrated that pathways including GPCR-ligand binding, neuronal system, signaling by WNT, translation, neuroactive ligand-receptor interaction, and TCF dependent signaling in response to WNT were differentially enriched in ELF3 low expression phenotype. Immune infiltration analysis showed that ELF3 expression was correlated with immune infiltrates. Conclusion ELF3 expression in OC patients was significantly associated with poor survival and immune infiltration and a promising prognostic biomarker in OC.

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“…In the SBT vs. HGSOC comparison, such genes included SLC7A , PIFO , RPL7A , and CRABP2 [ 57 – 61 ] (Table S 10 ). In fact, SLC7A2 serves as a potential biomarker and therapeutic target for ovarian cancer [ 62 ]. The remaining seven DEGs in the SBT vs. HGSOC comparison, while not previously reported in association with ovarian cancer, have cancer or disease-related functions.…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer

Jaiswal

Kaur

et al. 2021

BMC Cancer

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Background The heterogeneous subtypes and stages of epithelial ovarian cancer (EOC) differ in their biological features, invasiveness, and response to chemotherapy, but the transcriptional regulators causing their differences remain nebulous. Methods In this study, we compared high-grade serous ovarian cancers (HGSOCs) to low malignant potential or serous borderline tumors (SBTs). Our aim was to discover new regulatory factors causing distinct biological properties of HGSOCs and SBTs. Results In a discovery dataset, we identified 11 differentially expressed genes (DEGs) between SBTs and HGSOCs. Their expression correctly classified 95% of 267 validation samples. Two of the DEGs, TMEM30B and TSPAN1, were significantly associated with worse overall survival in patients with HGSOC. We also identified 17 DEGs that distinguished stage II vs. III HGSOC. In these two DEG promoter sets, we identified significant enrichment of predicted transcription factor binding sites, including those of RARA, FOXF1, BHLHE41, and PITX1. Using published ChIP-seq data acquired from multiple non-ovarian cell types, we showed additional regulatory factors, including AP2-gamma/TFAP2C, FOXA1, and BHLHE40, bound at the majority of DEG promoters. Several of the factors are known to cooperate with and predict the presence of nuclear hormone receptor estrogen receptor alpha (ER-alpha). We experimentally confirmed ER-alpha and PITX1 presence at the DEGs by performing ChIP-seq analysis using the ovarian cancer cell line PEO4. Finally, RNA-seq analysis identified recurrent gene fusion events in our EOC tumor set. Some of these fusions were significantly associated with survival in HGSOC patients; however, the fusion genes are not regulated by the transcription factors identified for the DEGs. Conclusions These data implicate an estrogen-responsive regulatory network in the differential gene expression between ovarian cancer subtypes and stages, which includes PITX1. Importantly, the transcription factors associated with our DEG promoters are known to form the MegaTrans complex in breast cancer. This is the first study to implicate the MegaTrans complex in contributing to the distinct biological trajectories of malignant and indolent ovarian cancer subtypes.

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SLC7A2 serves as a potential biomarker and therapeutic target for ovarian cancer

Cited by 23 publications

References 41 publications

SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

The Immune-Related Gene ELF3 is a Novel Biomarker for the Prognosis of Ovarian Cancer

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer

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