Development of a prognostic prediction model based on microRNA-1269a in esophageal cancer

Abstract

BACKGROUND Esophageal cancer (ESCA) is a heterogeneous cancer with variable outcomes that are challenging to predict. MicroRNA (miR)-1269a is a newly discovered non-coding RNA that shows promising prognostic prediction in other cancers, but its clinical value in ESCA remains unclear. AIM To explore the relationship between miR-1269a and its clinical value and to develop a nomogram to succinctly display this relationship. METHODS We analyzed the expression of miR-1269a in 125 ESCA tissue samples with complete clinical data and 52 normal tissue samples. We determined the prognostic value of miR-1269a for overall survival (OS) and cancer-specific survival (CSS) and evaluated the association between miR-1269a and clinical variables including tumor location, histologic grade, metastatic stage, and American Joint Committee on Cancer (AJCC) stage using multivariate Cox analysis. Additionally, we developed a nomogram for OS and CSS based on miR-1269a expression using age and AJCC stage and assessed its prognostic performance. Using Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analyses, we predicted the target genes of miR-1269a and analyzed their potential function in caner development. RESULTS The expression of miR-1269a was significantly higher in ESCA patients than healthy controls. Patients with high expression of miR-1269a showed poor prognosis in OS and CSS, suffered increased rates of low differentiation and metastasis, and exhibited tumor stage T3 + T4, positive lymph stage, and AJCC stage III + IV. The area under the receiver operating characteristic curve of miR-1269a was 0.716 for OS and 0.764 for CSS. Multivariate Cox analysis revealed that AJCC stage and miR-1269a were independent factors for OS and CSS. Combing with age, we constructed a nomogram for prognostic prediction. Additionally, our nomogram showed excellent predictive performance for OS and CSS after 3 years and 5 years and was easy to use. Ultimately, the functional analysis suggested that miR-1269a was mostly involved in the PI3K-AKT signaling pathway. CONCLUSION miR-1269a can be used as a potential indicator for the prognosis of ESCA patients. We developed an easy-to-use nomogram with excellent ESCA prognostic prediction for clinical use.

miR-1269a and miR-1269b: Emerging Carcinogenic Genes of the miR-1269 Family

“…miR-1269a is highly expressed in 9 cancers, including hepatocellular carcinoma (Wojcicka et al, 2014;Yang et al, 2014;Gan et al, 2015;Elemeery et al, 2017;Wang et al, 2019;Cho et al, 2020), lung cancer (Bao et al, 2018;Jin et al, 2018;Guo et al, 2020;Wang et al, 2020;Du et al, 2021;Le and Le, 2021), gastric cancer (Liu et al, 2019;Zhang K. et al, 2020), colon cancer (Bu et al, 2015;Xiong et al, 2021), esophageal cancer (Bai et al, 2021;Yu and Ren, 2021;Zhao et al, 2021), clear cell renal cell carcinoma (Qin et al, 2019;Zhan et al, 2021), head and neck squamous cell carcinoma (Nunez Lopez et al, 2018), glioma , and acute myeloid leukemia (Li and Ge, 2021). Highly expressed miR-1269a can promote cancer cell proliferation, migration, invasion, epithelial-mesenchymal transition, and inhibit cancer cell apoptosis (Table 1).…”

“…In lung cancer, highly expressed miR-1269a is significantly associated with lymph node metastasis and advanced TNM staging (Guo et al, 2020;Wang et al, 2020;Le and Le, 2021). In addition, in esophageal squamous cell carcinoma, highly expressed miR-1269a is significantly associated with poor tumor differentiation, lymph node metastasis, and TNM staging (Jang et al, 2017;Bai et al, 2021;Yu and Ren, 2021). ROC analysis showed that the AUC of miR-1269a expression was 0.640, indicating that the level of miR-1269a has a certain diagnostic value for hepatocellular carcinoma (Gan et al, 2015).…”

“…The expression levels of miR-1269a and miR-1269b are significantly related to the prognosis of cancer patients (Table 2). The high expression of miR-1269a is significantly associated with the lower overall survival (OS) of 6 kinds of cancer patients, including hepatocellular carcinoma (Cho et al, 2020), esophageal squamous cell carcinoma (Jang et al, 2017;Bai et al, 2021;Yu and Ren, 2021), lung cancer (Guo et al, 2020), clear cell renal cell carcinoma (Qin et al, 2019;Zhan et al, 2021), glioma and acute myeloid leukemia (Li and Ge, 2021). In hepatocellular carcinoma, high expression of miR-1269a is significantly associated with shorter disease-free survival (DFS) in patients with hepatocellular carcinoma (Cho et al, 2020) and lower cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (Yu and Ren, 2021).…”

Esophageal cancer screening, early detection and treatment: Current insights and future directions

“…Biomarkers such as microRNA signatures, circulating tumor DNA (ctDNA), and protein markers hold potential for identifying high-risk individuals and detecting esophageal cancer at its earliest, most treatable stages[ 44 - 46 ]. MicroRNA profiling can reveal specific expression patterns linked to esophageal cancer[ 45 , 47 ]. For example, the level of plasma microRNA-192-5p has been shown to predict the response to chemotherapy and the prognosis in patients with esophageal cancer[ 48 ].…”