Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Chemotherapy in Acute Myeloid Leukemia

Abstract

Background Acute myeloid leukemia (AML) is a highly heterogenous disease with varying clinical outcomes among patients. Epithelial-mesenchymal transition (EMT) is an important mechanism underlying cancer metastasis and chemotherapy resistance. However, few EMT-based signatures have been established to predict AML prognosis and treatment efficacy. Methods By conducting comparative RNA-seq analysis, we discovered the differential expression of EMT genes between AML patients with relapse and those without relapse. Based on the prognostic analysis of the differentially expressed EMT genes, a metastasis-related EMT signature (MEMTs) was constructed. An analysis was conducted on both TARGET and TCGA cohorts to explore the possible association between MEMTs and prognosis in AML. Three separate chemotherapy treatment cohorts were utilized to assess the predictive efficacy of MEMTs for chemotherapy response. In addition, the potential correlation between MEMTs and the tumor microenvironment was also investigated. Finally, random forest analysis and functional experiments were conducted to verify the key MEMTs gene associated with AML metastasis. Results Based on expression and prognostic analysis, we constructed MEMTs that include three EMT genes (CDH2, LOX, and COL3A1). Our findings suggested that the MEMTs could act as a prognostic factor for AML patients, and furthermore, it proved to be a predictor of their response to chemotherapy. Specifically, high MEMTs was associated with worse prognosis and poor response to chemotherapy, while low MEMTs was linked to better prognosis and higher response rates. Random forest and functional experiments demonstrate that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes. Conclusion The identification of MEMTs could potentially act as a predictor for the prognosis and the response to chemotherapy in AML patients. Individual tumor evaluation based on MEMTs could provide personalized treatment options for AML patients in the future.

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

“…Owing to its capacity to promote the invasion of cancer cells into neighboring tissues and their dissemination to distant regions, EMT plays a pivotal role in the process of carcinogenesis and the progression of malignancies. More speci cally, EMT encourages tumor cells to separate from their original site and to move into the bloodstream, where they eventually colonize secondary organs (Qu et al 2023). Several studies have indicated that EMT-related genes (ERGs) can be used as markers for predicting the prognosis of LUAD patients (Cui et al 2022; (Feng et al 2022).…”

RPF2 mediates the CARM1‑MYCN axis to promote chemotherapy resistance in colorectal cancer cells

“…In a previous study, we observed that RPF2 was widely overexpressed in CRC cells and found that coactivator-associated arginine methyltransferase 1 (CARM1), a downstream protein of RPF2, was involved in the epithelial-mesenchymal transition (EMT) in CRC ( 5 ). EMT has a major effect on the pathological mechanisms of tumor cells and a large number of studies have demonstrated that it is associated with cell proliferation, apoptosis and drug resistance ( 6 – 11 ). Dysregulated expression of the ATP-binding cassette (ABC) superfamily of transporters is the main reason why tumor cells increase their ability to efflux cytotoxic drugs, leading to resistance to chemotherapeutic agents ( 12 ).…”