Abstract
Background: Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy. Methods: A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis. Results: We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD. Conclusion: The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.
Highlights
Colon adenocarcinoma (COAD), one of the most prevalent cancers worldwide, has become a leading cause of cancer death (Bray et al, 2018; Miller et al, 2019)
The COAD patients in Gene Expression Omnibus (GEO) datasets were divided into two groups according to the patient’s survival status (Figure 1A)
The correlation analysis between Homeobox C11 gene (HOXC11) (Figure 4E), PCOLCE2 (Figure 4F), MMP7 (Figure 4G), Yes-associated protein 1 (YAP1) (Figure 4H) and Epithelial-to-mesenchymal transition (EMT)-related genes were performed for further exploring targeted genes; the results indicated that these four genes were tightly correlated with both ferroptosis and EMT process
Summary
Colon adenocarcinoma (COAD), one of the most prevalent cancers worldwide, has become a leading cause of cancer death (Bray et al, 2018; Miller et al, 2019). The 5-years survival rates for patients with early stage cancer are approximately 90%, whereas for patients diagnosed with advanced-stage metastatic disease is only 10% (Kuipers et al, 2015), indicating that metastasis is a critical cause of death for cancer patients. There is an urgent need to identify novel prognostic biomarkers related to the tumor metastasis, which may facilitate the timely diagnosis and application of appropriate individual treatments for COAD patients. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy
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