NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) protein is located in the mitochondria and can regulate cell proliferation. Some studies have shown that the high NDUFA4L2 expression is linked with poor prognosis and cancer progression in various patients with cancers. However, the correlation between NDUFA4L2 and pan-cancer is unknown. In this study, we used the databases and investigated the expression and variation of NDUFA4L2 in many cancers in detail to determine its diagnostic and prognostic values. We also validated the oncogenic capability of NDUFA4L2 in colon cancer by experiments or tissue microarray. In most cancers, NDUFA4L2 expression levels are upregulated, and a high level of NDUFA4L2 expression is associated with poor OS. In addition, the results showed that 10 proteins and 30 genes were correlated to NDUFA4L2. An additional analysis demonstrated that these genes and proteins exhibited either negative or positive correlations with specific pathways. Moreover, we discovered that NDUFA4L2 expression was related to tumor stemness, MSI, TMB, immune cell infiltration and ROS production. Our results show that NDUFA4L2 affects the development and mitochondrial function of colon cancer cell lines. Finally, we identified that NDUFA4L2 was sensitive to 10 anticancer drugs. Our study suggest that NDUFA4L2 could serve as a prognostic and therapeutic biomarker for most cancer, including colon cancer.
Keywords: NDUFA4L2; biomarker; colon cancer; mitochondrial function; pan‐cancer.
© 2025 Federation of American Societies for Experimental Biology.