Comprehensive pan-cancer analysis reveals ENC1 as a promising prognostic biomarker for tumor microenvironment and therapeutic responses

Sep 21, 2026

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Comprehensive pan-cancer analysis evaluates how ENC1 expression relates to prognosis and immune checkpoint inhibitor (ICI) response across multiple cancers. Compared with normal tissues, most tumors show increased ENC1 levels, with gene mutation as the most common variation and positive relationships between CNV and ENC1. ENC1 overexpression associates with worse clinical outcomes and GSEA-linked tumor-promoting pathways, while ENC1 is negatively linked to immune cell infiltration and shows coordinated associations with immunomodulators and immune checkpoint inhibitor expression. Functional inhibition of ENC1 suppresses proliferation and migration in breast cancer, pancreatic cancer, and glioma cells.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Materials and methods

Data collection and processing

Analysis of copy number variation (CNV) and methylation

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Comprehensive pan-cancer analysis reveals ENC1 as a promising prognostic biomarker for tumor microenvironment and therapeutic responses Zhenyu Cao1, Jinfeng Zhu2, Zicheng Wang1,3, Yuhuai Peng1 & Liyun Zeng1􀀍 Accumulating research showed that ENC1 plays a critical role in maintaining the physiological functions. However, little is known about its role in predicting prognosis and immunotherapy response across cancers. In our results, compared to normal tissues, most cancer tissues exhibit increased ENC1 expression. We found that the most common type of genetic variation was gene mutation. In addition, a positive correlation was found between CNV and ENC1 expression. Moreover, the overexpression of ENC1 was positively correlated with poor clinical outcomes. The GSEA results showed that ENC1 is closely correlated with tumor-promoting biological functions in most cancers. ENC1 is also closely negatively associated with the infiltration levels ofT cells, activated NK cells, and B cells. Most immunomodulators are positively associated with ENC1 . Further, we verified that inhibition of ENC1 expression suppressed the proliferation and migration of breast cancer, pancreatic cancer and glioma cells. In conclusion, our study demonstrated that ENC1 plays a protumorigenic role in most cancers. Additionally, ENC1 is closely correlated with tumor microenvironment features and immune checkpoint inhibitors expression. Overall, ENC1 could serve as a promising potential prognostic biomarker in various tumors. Keywords ENC1, Immunotherapy, Pan-cancer, Immunomodulators, Tumor immune infiltration, Prognostic biomarker In recent years, cancer has gained prominence as a leading cause of death1,2. Often, cancer patients with advanced stages of the disease have a better quality of life and an increased chance of survival because new diagnostic and treatment methods have emerged over the past few decades3,4. In particular, immune checkpoint inhibitors (ICIs) has advanced significantly in treating malignant tumors5,6. However, a significant part of cancer patients still poorly response to ICI therapy. Considering the potential mechanisms of immunotherapy, the tumor immune microenvironment (TIME) is significant for the therapeutic response to ICIs. For example, in“hot” tumors, the massive T cell infiltration leads to the effectiveness ofICIs therapy, while the “cold” tumors do the opposite7. Within the TME, all immune components are collectively defined as TIME due to their unique internal interactions and essential roles in tumor biology, which contains innate immune cells, adaptive immune cells, extracellular immune factors, and cell surface molecules8. What’s more, the composition of immune cells in TIME also affects the prognosis of malignant tumors. For example, triple-negative breast cancer (TNBC) with less T cell infiltration generally has worse prognosis than those with more T cell inflamed9. But, thereis still a lack of suitable prognostic and therapeutic markers, so appropriate therapeutic modalities strategies for predicting clinical outcomes are urgently needed, and this can be accomplished by identifying suitable biomarkers10. Pan-cancer analysis is based on the mining of public databases to analyze differential gene expression, gene characteristics and immunological associations in most types of tumors to provide valuable diagnostic, prognostic and immunotherapeutic information11. 1Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, China. 2Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, Hunan Province, China. 3Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China. 􀀍 email: [zengliyun1994@csu.edu.cn]

FAQs

What does the study report about ENC1 expression across cancers?

Compared with normal tissues, most cancer tissues show increased ENC1 expression.

How is ENC1 linked to prognosis in patients?

ENC1 overexpression is positively correlated with poor clinical outcomes, and it shows close relationships with tumor-promoting biological functions in most cancers.

What is the relationship between ENC1 and tumor immune features?

ENC1 is negatively associated with infiltration levels of T cells, activated NK cells, and B cells, and it is correlated with immunomodulator and immune checkpoint inhibitor expression. Inhibiting ENC1 suppresses proliferation and migration of several cancer cell types.

Sep 21, 2026

Uploaded by Sage