Patients with cancer encounter a heightened short-term likelihood of cardiovascular complications, whereas individuals suffering an acute myocardial infarction (AMI) tend to show an increased rate of cancer diagnoses. With clinical resources often limited, pinpointing overlapping biomarkers provides a practical and economical strategy for risk evaluation, reducing the need for numerous independent diagnostic procedures. Consequently, recognizing biomarkers that simultaneously relate to cancer survival and AMI risk is essential. Our research indicates that monocyte-associated markers—WEE1, PYHIN1, SEC61A2, and HAL—may function as useful indicators for both cancer prognosis and AMI. Using an innovative computational formula, we assessed mRNA expression patterns in samples from patients with AMI and cancer, which allowed us to construct a new expression-based risk index. When participants were separated into high- and low-risk categories using the median score, Kaplan–Meier curves revealed clearly worse survival for the high-risk subsets in cancer datasets. Additionally, calibration plots, decision curve analysis (DCA), and clinical impact curves further supported the strong diagnostic performance of this risk model for AMI. A notable finding was the mutual activation of the Notch signaling cascade, offering insight into shared high-risk features underlying both diseases. We also confirmed consistent expression differences of these genes in cell lines and clinical tissues, reinforcing their value as candidate biomarkers. Overall, our work highlights the potential of mRNA-based indicators and underscores the importance of continued validation and methodological refinement.
