SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

Abstract

Recent studies have reported that SERPINE2 contributes to the development of various cancers. However, its association with urothelial carcinoma (UC) remains unclear. In this study, data on urinary bladder UC (UBUC) cases from The Cancer Genome Atlas (TCGA) database were used to investigate the prognostic value of SERPINE2 mRNA expression. Then, SERPINE2 expression was analyzed with tissue microarrays constructed from 117 upper tract UC (UTUC) and 84 UBUC tissue specimens using immunohistochemical staining. Results were compared to clinicopathologic data by multivariate analysis. In the TCGA database, high SERPINE2 mRNA expression indicated a poor prognosis in patients with UBUC. Furthermore, Mann–Whitney U test showed that high SERPINE2 immunoexpression was significantly associated with adverse pathologic parameters including invasion, high grade, coexistence of UC in situ, and advanced pT stage (all p < 0.05, except for a marginal association with high-grade UBUC, p = 0.066). Kaplan–Meier analysis revealed that high SERPINE2 expression was associated with worse overall survival (OS; UTUC, p = 0.003; UBUC, p = 0.014) and disease-free survival (UTUC, p = 0.031; UBUC, p = 0.033). Moreover, multivariate analysis identified high SERPINE2 expression as an independent prognostic factor for OS (UTUC, p = 0.002; UBUC, p = 0.024). Taken together, our findings demonstrated that increased SERPINE2 expression is associated with adverse pathologic features and may serve as a prognostic biomarker for UC.

Differential Proteome Profiling Analysis under Pesticide Stress by the Use of a Nano-UHPLC-MS/MS Untargeted Proteomic-Based Approach on a 3D-Developed Neurospheroid Model: Identification of Protein Interactions, Prognostic Biomarkers, and Potential Therapeutic Targets in Human IDH Mutant High-Grade Gliomas

“…They are involved in calcium homeostasis. A novel study conducted by Godinez et al (2022) has revealed that neuroserpin plays an important role in mediating neurite outgrowth and axonal development as well as in maintaining normal synaptic plasticity through its inhibitory effects on the tissue plasminogen activator (tPA) in the CNS, thereby preventing tPA interaction with the NMDA receptor-mediated calcium influx, which contributes to excitotoxic neuronal apoptosis. , The elevated expression of serpin superfamily proteins was associated with low survival and increased recurrence rates …”

“…95,96 The elevated expression of serpin superfamily proteins was associated with low survival and increased recurrence rates. 97 Another identified protein encoded by CAMK (2A, 2B, 2D) is a member of the N-methyl-D-aspartate receptor (NMDAR) signaling complex in excitatory synapses regulating the NMDAR-dependent potentiation of the AMPA receptor and therefore excitatory synaptic transmission. 34 It acts autonomously after ca 2+ /calmodulin binding and autophosphorylation and is involved in synaptic plasticity, neurotransmitter release, and long-term potentiation.…”

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

“…The mouse model of breast tumor heterogeneity demonstrated that SERPINE2 provokes tumor cells to form vascular networks that mimic blood vessels to facilitate tumor cells penetration and metastasis, indicating that SERPINE2 is a dominant driver of metastatic progression [ 30 ]. Simultaneously, high SERPINE2 expression was an independent poor prognostic factor in oral squamous cell carcinoma (OSCC), lung adenocarcinoma, urothelial carcinoma and endometrial cancer [ 31 , 32 , 33 , 34 ], and SERPINE2 was identified as a promising therapeutic target in melanoma metastasis and in the radio-resistance of lung cancer. SERPINE2 promotes radio resistance by mediating the interaction of MRE11 with ATM to induce ATM phosphorylation in homologous recombination (HR)-mediated double strand break (DSB) repair [ 28 , 35 ].…”

Homologous recombination repair gene‐based risk model predicts prognosis and immune microenvironment for primary lung cancer after previous malignancies

“…Serine protease inhibitor branch E member 2 (SERPINE2), also known as protease ligand protein‐1, is a member of the serine protease inhibitor superfamily. Studies have shown that aberrant expression of SERPINE2 contributes to tumorigenesis and tumor invasion in a variety of cancers, including breast, pancreatic, colorectal, gastric, testicular, cutaneous melanoma, osteosarcoma, thyroid, oral squamous cell, endometrial, esophageal squamous cell, lung, and hepatocellular carcinomas 46–51 . In lung cancer, SERPINE2 is involved in tumor treatment resistance by attenuating DNA damage.…”