Construction and validation of prognostic prediction established on N6-methyladenosine related genes in cervical squamous cell carcinoma

Abstract

Background: Cervical cancer (CESC) is the second most common cancer death in middle-aged women.The N6-methyladenosine (m6A) plays an essential role in the epitranscriptomics of cancer and affects immune cell infiltration. Our study used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data to construct and validate prognostic prediction established on m6A-related genes in CESC. Methods: We gained gene expression and clinical characteristics from TCGA and GEO. After differentially expression analysis of the m6A-related genes, we identified eight genes of CESC development. Next, we executed consensus clustering to analyze CESC types established on the differential expression of the m6A-related genes and found different subtypes significantly correlate with survival prognosis, immune microenvironment, and PD-L1 expression. Then, based on Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, a five-gene (IGF2BP1, IGF2BP2, HNRNPA2B1, YTHDF1, RBM15) predictive model was built in the TCGA training cohort. Finally, we checked the predictive model with survival analysis and receiver operating characteristic (ROC) curve both in the training cohort (TCGA) and in the validation cohort (GSE44001). We found the expression and variation of the five genes significantly correlate with immune cell infiltration. Results: The CESC could be divided into subtypes according to eight expression m6A-related genes. Different subtypes are related to various immune cells, immune scores, and the expression of the PD-L1. We develop a risk prediction model: risk score = (0.023558929) * Exp IGF2BP1 + (0.021148829) * Exp IGF2BP2 + (0.045035491) * Exp HNRNPA2B1 + (−0.106566550) * Exp YTHDF1 + (−0.001037932) * Exp RBM15.Moreover, different m6A-related genes significantly correlated with immune cells.Conclusions: The m6A-related genes risk prediction model plays an essential role in predicting CESC patients. The m6A-related genes affected the immune cell infiltration in CESC. These results suggest that the expression of m6A-related genes may influence the immune therapy of CESC and be the potential therapeutic target.

Elucidating prognosis in cervical squamous cell carcinoma and endocervical adenocarcinoma: a novel anoikis-related gene signature model

“…Understanding mechanisms like anti-apoptosis, cell invasion, and immune evasion is vital for developing targeted therapies. Although models based on ferroptosis, pyroptosis, and N6-methyladenosine have been proposed, their predictive efficacy is insufficient, necessitating new models (23)(24)(25). Anoikis serves as a natural barrier against metastasis by preventing the colonization of tumor cells at non-native sites.…”

HNRNPA2B1 promotes oral squamous cell carcinogenesis via m6A‐dependent stabilization of FOXQ1 mRNA stability

“…For example, HNRNPA2B1 mainly boosts malignant phenotypes of cancer cells in ESCC, cervical squamous cell carcinoma, adrenocortical carcinoma, breast cancer, etc. [38][39][40][41][42][43][44][45] FOXQ1 is widely expressed in many tissues. FOXQ1 can induce cancers by activating oncogenes in the nucleus.…”

“…Dysregulation of HNRNPA2B1 may give rise to various tumors, neurodegenerative diseases, and autoimmune diseases. For example, HNRNPA2B1 mainly boosts malignant phenotypes of cancer cells in ESCC, cervical squamous cell carcinoma, adrenocortical carcinoma, breast cancer, etc 38–45 …”

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“…Understanding mechanisms like anti-apoptosis, cell invasion, and immune evasion is vital for developing targeted therapies. Although models based on ferroptosis, pyroptosis, and N6-methyladenosine have been proposed, their predictive efficacy is insufficient, necessitating new models (23)(24)(25). Anoikis serves as a natural barrier against metastasis by preventing the colonization of tumor cells at non-native sites.…”