GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

Reyna-Hernández, Ma. A.; Alarcón‐Romero, Luz del Carmen; Ortíz-Ortíz, Julio; Illades‐Aguiar, Berenice; Jiménez‐López, Marco Antonio; Ocampo-Bárcenas, Azucena; Morrugares-Ixtepan, Martin O.; Torres-Rojas, Francisco I

doi:10.1369/00221554221101662

Cited by 11 publications

(12 citation statements)

References 37 publications

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“…[ 18 ] Found that SLC2A1 has abundant methylation sites and was associated with immunosuppression in colon cancer. High expression of SLC2A1 in high-grade CIN with high-risk human papillomavirus (HR-HPV) infection indicates a high risk of cervical cancer [ 19 ]. This study also confirms that SLC2A1 and CA2 are highly expressed, and that CUX1 is weakly expressed, in cervical cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer

et al. 2023

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Purpose To investigate the prognostic value of N6-methyladenosine (m6A)-, 5-methylcytosine (m5C)-, and N1-methyladenosine (m1A)-related genes in cervical cancer (CESC) and predicting immunotherapy response. Methods We downloaded cervical cancer mRNA expression profiles, clinical data, and m6A, m5C, m1A-related genes from public databases, and subjected them to serial bioinformatics analysis and clinical sample validation. Results Differential analysis revealed 106 methylation-related differential genes (MEDs), including 44 differentially downregulated and 62 upregulated genes. We then obtained methylation models containing 10 genes by univariate and multifactorial COX analysis. High risk genes with HR > 1 include IQGAP3, PTBP1, STAC3, CUX1, SLC2A1, and CA2, and low risk genes with HR < 1 include IGBP1, DUOX1, CHAF1A, and STAC3. We verified the accuracy of the model from inside TCGA and outside GSE39001 (AUC = 0.729). K-M analysis showed shorter survival times in the High-risk group, and Immunocytic infiltration analysis showed model genes closely associated with six immune cells. The high-risk group may benefit more effectively from immunosuppressive therapy, especially anti-CTLA-4 therapy ( p < .05). We also screened nine drugs for potential treatment and verified the expression of three key genes SLC2A1, CUX1, and CA2 using immunohistochemistry and RT-qPCR experiments with clinical samples. Conclusion We identified a prognostic model using m6A/m5C/m1A-related genes in cervical cancer, which can predict survival time and correlate with immune cell infiltration. Additionally, anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer. KEY MESSAGES Cervical cancer still has a high mortality rate, we aim to establish a strong prognostic index and new treatment goals for improving patient survival. The role of three types of RNA methylation modifications, m6A, m5C, and m1A, in cervical cancer, remains unknown. Therefore, it is essential to explore the potential molecular mechanisms of m6A, m5C, and m1A methylation regulation in cervical cancer. We also screened nine drugs for potential treatment and anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer. We verified the expression of three key genes SLC2A1, CUX1, and CA2

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Section: Discussionmentioning

confidence: 99%

RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer

et al. 2023

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“…These genes are known to code for proteins involved in processes such as metabolic reprogramming [ 9 , 22 ], angiogenesis [ 28 ], cell migration, invasion, and metastasis [ 29 , 30 ]. High expression of GLUT1, LDHA, and MCT4 proteins has been observed in biopsies from patients with invasive cervical cancer [ 31 ]. Additionally, LDHA inhibition has resulted in cell cycle inhibition and apoptosis in nasopharyngeal carcinoma [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of HIF-1α and Genes Involved in Glucose Metabolism Is Increased in Cervical Cancer and HPV-16-Positive Cell Lines

et al. 2022

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Cervical cancer (CC) is the most common cancer in women in the lower genital tract. The main risk factor for developing CC is persistent infection with HPV 16. The E6 and E7 oncoproteins of HPV 16 have been related to metabolic reprogramming in cancer through the regulation of the expression and stability of HIF-1α and consequently of the expression of its target genes, such as HIF1A (HIF-1α), SLC2A1 (GLUT1), LDHA, CA9 (CAIX), SLC16A3 (MCT4), and BSG (Basigin or CD147), which are involved in glucose metabolism. This work aimed to evaluate the expression of HIF-1α, GLUT1, LDHA, CAIX, MCT4, and Basigin in patient samples and CC cell lines. To evaluate the expression level of HIF1A, SLC2A1, LDHA, CA9, SLC16A3, and BSG genes in tissue from patients with CC and normal tissue, the TCGA dataset was used. To evaluate the expression level of these genes by RT-qPCR in CC cell lines, HPV-negative (C-33A) and HPV-16-positive (SiHa and Ca Ski) cell lines were used. Increased expression of HIF1A, SLC2A1, LDHA, SLC16A3, and BSG was found in Ca Ski and CA9 in SiHa compared to C-33A. Similar results were observed in CC tissues compared to normal tissue obtained by bioinformatics analysis. In conclusion, the expression of HIF-1α, GLUT1, LDHA, CAIX, MCT4, and BSG genes is increased in CC and HPV-16-positive cell lines.

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“…LDHA is a gene encoding a key glycolytic enzyme ( Tang et al, 2022 ). Reyna-Hernández et al found increased expression of LDAH in invasive cervical cancer ( Reyna-Hernández et al, 2022 ). Our research, which combined these six genes to create a predictive model, could help us better understand tumor cells.…”

Section: Discussionmentioning

confidence: 99%

The combined prognostic model of copper-dependent to predict the prognosis of pancreatic cancer

2022

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Purpose: To assess the prognostic value of copper-dependent genes, copper-dependent-related genes (CDRG), and CDRG-associated immune-infiltrating cells (CIC) for pancreatic cancer.Methods: CDRG were obtained by single-cell analysis of the GSE156405 dataset in the Gene Expression Omnibus (GEO) database. In a ratio of 7:3, we randomly divided the Cancer Genome Atlas (TCGA) cohort into a training cohort and a test cohort. Tumor samples from the GSE62452 dataset were used as the validation cohort. CIBERSORT was used to obtain the immune cell infiltration. We identified the prognostic CDRG and CIC by Cox regression and the least absolute selection operator (LASSO) method. The clinical significance of these prognostic models was assessed using survival analysis, immunological microenvironment analysis, and drug sensitivity analysis.Results: 536 CDRG were obtained by single-cell sequencing analysis. We discovered that elevated LIPT1 expression was associated with a worse prognosis in pancreatic cancer patients. EPS8, CASC8, TATDN1, NT5E, and LDHA comprised the CDRG-based prognostic model. High infiltration of Macrophages.M2 in pancreatic cancer patients results in poor survival. The combined prognostic model showed great predictive performance, with the area under the curve (AUC) values being basically between 0.7 and 0.9 in all three cohorts.Conclusion: We found a cohort of CDRG and CIC in patients with pancreatic cancer. The combined prognostic model provided new insights into the prognosis and treatment of pancreatic cancer.

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GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

Cited by 11 publications

References 37 publications

RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer

RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer

Expression of HIF-1α and Genes Involved in Glucose Metabolism Is Increased in Cervical Cancer and HPV-16-Positive Cell Lines

The combined prognostic model of copper-dependent to predict the prognosis of pancreatic cancer

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