Solute Carrier Family 7 Member 11 (SLC7A11) is a Potential Prognostic Biomarker in Uterine Corpus Endometrial Carcinoma

Abstract

Background Uterine corpus endometrial carcinoma (UCEC) is a common type of gynecological cancers, second only to cervical cancer in incidence. Thus, it is necessary to develop effective therapies and identify biomarkers for its prognosis. Solute carrier family 7 member 11 (SLC7A11) is well known for its role in maintaining the intracellular glutathione level and preventing oxidative-stress-induced cell death. However, the association between SLC7A11 expression and prognosis as well as the correlation between tumor-infiltrating immune cells (TIICs) and immunotherapy of UCEC has rarely been reported. This study aims to evaluate the prognostic significance and immune cell infiltration level of SLC7A11 in UCEC. Methods Bioinformatics analysis tools and databases, including R software, National Center for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), GEPIA2, Sangerbox, Kaplan–Meier (K-M) Plotter, TISIDB, and TIMER2, were utilized to measure the expression level and clarify the clinical significance of SLC7A11 in UCEC. Results SLC7A11 expression was dramatically up-regulated in UCEC patients and associated with prognosis. DNA methylation levels in the SLC7A11-promoter region were significantly higher in normal participants than in patients with UCEC. We also showed that SLC7A11 overexpression was associated with TIICs, immune checkpoint blockers (ICBs), and immunotherapy response in UCEC. The half-maximal inhibitory concentration (IC50) results obtained with the cohort from TCGA showed that Z-VAD-FMK (Caspase inhibitor), S-Triphenylmethyl-L-cysteine (S-Trityl-L-cysteine), and TAE684 (ALK inhibitor) had higher IC50 values in low-expression patient (p < 0.05). Conclusion SLC7A11 overexpression is associated with favorable prognosis of patients with UCEC and is associated with TIICs and the responses to immunotherapy.

Differences in single gene expression patterns and signaling pathways between Black and White patients in high grade endometrioid endometrial cancer independent of BMI

“…The DMRT protein-coding gene ultimately leads to enabling of sequence-specific double-stranded DNA binding activity; DMRT1 has been shown to play a role in cell reprogramming in germ cell tumors ( Taguchi et al, 2021 ), though not specifically in EC to our knowledge. The SLC family encodes for numerous solute-carrying proteins; SLC7A11 has been implicated as a possible prognostic marker in EC ( Fang et al, 2023 ) while several are implicated in ovarian cancer cell line resistance ( Januchowski et al, 2013 ). Further work is necessary to understand the validity and implications of these gene differences.…”

Ferroptosis, Metabolic Rewiring, and Endometrial Cancer

“…Thus, metabolic changes during obesity may sensitize EC to ferroptosis inducers. EC exhibits glucose and glutamine dependency, as well as SLC7A11 overexpression [121][122][123]. This relates to EC cell metabolic rewiring and sensitivity to ferroptosis (Figure 6).…”

“…Thus, this reaction not only utilizes glucose but also increases ROS [129]. Glucose oxidase can be immobilized on nanoparticles and then specif- EC exhibits glucose and glutamine dependency, as well as SLC7A11 overexpression [121][122][123]. This relates to EC cell metabolic rewiring and sensitivity to ferroptosis (Figure 6).…”

“…EC exhibits glucose and glutamine dependency, as well as SLC7A11 overexpression [ 121 , 122 , 123 ]. This relates to EC cell metabolic rewiring and sensitivity to ferroptosis ( Figure 6 ).…”

Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients

“…Additionally, they showed a relationship between SLC7A11 overexpression and the immune checkpoint blocker (ICB), tumour immune induction complex (TIIC), and immunotherapy responsiveness. As a result, SLC7A11 overexpression is linked to both the effectiveness of immunotherapy and a good prognosis for patients with UCEC [113].…”