ENO1, a glycolytic enzyme acting as a plasminogen receptor on cell surfaces, contributes to cancer cell proliferation, migration, invasion, and metastasis. 213 ENO1 overexpression has been documented in a broad range of cancers including lung, breast, liver, and others, and is usually associated with poor prognosis. This overexpression can contribute to the metabolic changes associated with cancer cells, as they regularly rely on glycolysis for energy production. In breast cancer, enhanced ENO1 expression has been associated with greater tumor size and a shorter disease-free interval. Patients with lung cancer overexpressing ENO1 also exhibited poor clinical outcomes, with shorter overall survival. ENO1 overexpression in hepatocellular carcinoma correlated positively with venous invasion. ENO1 overexpression in multiple cancer types, its localization at the cancer cell surface, and its targetability make this protein a rising cancer biomarker and potential target for therapeutic agents. 219 SETD2 is a gene that encodes an enzyme involved in histone modification, specifically histone H3 lysine 36 (H3K36) methylation. This gene plays a crucial role in epigenetic regulation and has been implicated in various cellular processes, including DNA repair, transcriptional regulation, and chromatin organization. Mutations in SETD2 can be both loss-of-function and gain-of-function mutations, affecting its histone methylation activity. Frequent mutations have been reported in cancers like clear cell renal cell carcinoma, 220 acute lymphoblastic leukemia, 221 glioblastoma, 222 and others. The correlation between SETD2 deleterious mutation and tumor mutation burden has placed it in the spotlight as a promising prognostic biomarker for cancer immune checkpoint inhibitor treatment. The cell adhesion protein nectin-4 also emerges as a favorable prognostic blood-based biomarker and is known to be overexpressed in several cancer types, including breast, 224 ovarian, 225 endometrial, 226 urothelial, 227 and certain subtypes of bladder cancer . High levels of nectin-4 expression have been correlated with more aggressive cancer behavior, poor prognosis, and shorter survival rates, making it also an emerging prognostic biomarker. For example, in a multivariate clinical analysis of triple-negative breast cancer survival rate, nectin-4 has been highlighted as a favorable breast cancer prognostic marker. Gasdermin E (GSDME), also known as DFNA5 (Deafness, Autosomal Dominant 5), is a protein that is involved in programmed cell death, specifically pyroptosis, a form of cell death in response to infection or cellular stress. GSDME has been found highly expressed in most malignant cancers, and an obvious relationship exists between GSDME levels and survival prognosis of cancer patients. Studies have also shown that GSDME methylation is a valuable molecular biomarker in cancer, specifically in breast cancer diagnoses, 232 with a recent report suggesting importance in a variety of other cancer types as well. The prominent expression and methylation properties of GSDME in diverse cancers make it an emerging favorable prognostic biomarker with a tremendous potential. IGF2BP2, protein belonging to the family of RNA-binding proteins, plays a role in posttranscriptional regulation of gene expression by binding to specific target mRNAs, thereby influencing their stability and translation. While IGF2BP2 is more commonly associated with metabolic functions and type 2 diabetes, it has also been studied in the context of cancer. Its overexpression can lead to the stabilization and increased translation of specific mRNA targets and in some cases can promote tumorigenesis and cancer progression by enhancing the expression of oncogenic genes. In the context of hepatocellular carcinoma, IGF2BP2 overexpression may be linked to cancer development. The expression levels of IGF2BP2 in tumor tissues and its correlation with clinical outcomes are areas of active research.