Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma

Abstract

Background: Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is strongly associated with poor patient prognosis, it has rarely been reported in uterine corpus endometrial carcinoma (UCEC).Methods: We explored the role of MCM4 in UCEC through multi-omics analysis, including gene expression levels, survival prognosis, the biological function of interacting proteins, immune infiltration, and diagnostic value. Finally, these results were confirmed by biological experiments.Results: MCM4 was highly expressed in various malignancies including UCEC compared to normal samples and was associated with poor prognosis in patients with UCEC [including OS (HR = 1.74, p = 0.009), PFI (HR = 1.73, p = 0.002), PFI (HR = 2.23, p = 0.003)]. In the Cox regression analysis, MCM4 was an independent prognostic biomarker. Further studies showed those interacting proteins of MCM4 were enriched in DNA repair and cell cycle. Moreover, high expression of MCM4 was accompanied by lower infiltration of immune cells such as Treg cells and B cells. The distribution of MCM4 expression in molecular and immune subtypes was significantly different (p < 0.05), with high expression in the copynumber high (CN_HIGH) molecular subtype and the IFN-gamma dominant (C2) immune subtype. RT-qPCR and immunohistochemistry results also showed that MCM4 expression was significantly upregulated in endometrial cancer tissues and negatively correlated with patient prognosis (p < 0.05). Subsequent biological experiments confirmed that MCM4 promoted cell growth and invasion and inhibited apoptosis in vitro.Conclusion: Therefore, MCM4 could be a new potential biomarker for UCEC.

Multi-omics pan-cancer analyses identify MCM4 as a promising prognostic and diagnostic biomarker

“…This association spanned the different pathological stages of six types of cancer, as well as the G1, S and G2 phases of the cell cycle. Our results, which are consistent with previous studies, suggest that MCM4 may contribute to the development of cancer 21 , 43 – 47 .…”

“…Ultimately, these mechanisms contribute to the development of cancer and various developmental abnormalities 1,2 . Limited studies have employed bioinformatics approaches to examine the function of MCM4 in particular tumor types [21][22][23][24][25][40][41][42] , and a comprehensive pan-cancer analysis has yet to be undertaken. This investigation addresses this knowledge deficit by providing an exhaustive assessment of MCM4 across diverse cancer types, encompassing its expression levels in both normal and malignant tissues, gene mutation profiles, immune cell infiltration, involvement in biological processes, prognosis, potential as a diagnostic marker and drug sensitivity.…”

“…Research has demonstrated that this complex possesses intrinsic DNA helicase activity, a vital enzymatic function that participates in a wide range of cellular processes including replication initiation, DNA repair, and recombination 18 , 20 . Increasing evidence has confirmed the overexpression of MCM4 in several cancers like hepatocellular carcinoma, soft-tissue sarcoma, esophageal cancer, glioma and uterine corpus endometrial carcinoma 21 – 26 . The overexpression of MCM4 may lead to aberrations in the cell cycle, promoting uncontrolled cell proliferation, thus accelerating tumor growth and metastasis.…”

Novel DNA Damage-Related Subtypes Characterization Identifies Uterine Corpus Endometrial Carcinoma (UCEC) Based on Machine Learning

“…Immunotherapy is emerging as a potentially useful treatment method since it has high specificity, long-time benefits, and few adverse effects [ 7 ]. The response rate of immune checkpoint blockade treatment is quite low in patients with UCEC due to the vast heterogeneity of the disease, which includes clinicopathologic parameters, molecular features, and immunological microenvironment [ 8 ]. Therefore, identifying the fundamental benefits in patients is essential for the advancement of immunotherapy considering UCEC variability.…”