NF2 is a candidate diagnosis, prognostic, and immunotherapeutic biomarker: a systematic pan-cancer analysis

Our plain-English summary of NF2 is a candidate diagnosis, prognostic, and immunotherapeutic biomarker: a systematic pan-cancer analysis, by H. Zhang, J. Liu (Translational Cancer Research, 2024).

The study

• Authors: H. Zhang, J. Liu
• Journal: Translational Cancer Research
• Published: 2024;13(2):1026-1042
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Neurofibromin 2 (NF2) regulates diverse cellular events such as transcription, translation, ubiquitination, and micro-RNA biosynthesis. Previous evidence revealed that aberrant expression of NF2 contributes to tumorigenesis in mesothelioma, meningioma, and breast cancer. However, there is no comprehensive pan-cancer analysis to explore NF2's function in cancer diagnosis, prognosis, and immunological prediction.

Methods: By extensive use of data profiles from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) project, Cancer Cell Line Encyclopedia (CCLE), CIBERSORT, Human Protein Atlas (HPA), and cBioPortal, we employed various bioinformatics methods to explore the role of NF2 in pan-cancer, including analyzing the association between NF2 and tumor diagnosis, prognosis, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the co-expression relationship between NF2 expression with RNA modification genes was also constructed.

Results: Our research indicated that NF2 was highly expressed in most kinds of tumors. NF2 showed an early diagnosis value in 13 types of tumors and was significantly associated with the prognosis in most tumors. The results also verified that NF2 expression was associated with most immune-related cells and signaling pathways in pan-cancer, especially in diffuse large B-cell lymphoma and ovarian serous cystadenocarcinoma. Furthermore, NF2 gene expression was associated with TMB and MSI in many tumors.

Conclusions: Our study reveals that NF2 might be helpful in tumor early diagnosis and prognosis evaluation. The expression of NF2 is highly associated with the tumor immune microenvironment. Additionally, NF2 is a potential biomarker for predicting the efficacy of immune checkpoint inhibitors therapy. Therefore, NF2 can be a promising diagnostic, prognostic, and immunotherapeutic biomarker for many types of tumors.

2024 Translational Cancer Research. All rights reserved.

In plain English

This was a computer-based (bioinformatics) analysis of public gene databases. It did not study asbestos exposure. The authors examined the NF2 gene, which makes a protein called Merlin, across many cancer types, mainly using The Cancer Genome Atlas. NF2 expression differed significantly between tumor and normal tissue in 25 cancers and was higher in tumors in 21 of them. Links between NF2 levels and survival ran in opposite directions in different cancers. In a gene-alteration analysis covering 10,967 patients with 32 cancer types, NF2 mutations were most frequent in pleural mesothelioma (22.99%). In a disease-specific survival analysis, higher NF2 levels went with better survival in several cancers, including mesothelioma. NF2 levels were also associated with immune-cell measures, tumor mutational burden and microsatellite instability in various cancers. The authors concluded that NF2 is a promising diagnostic, prognostic and immunotherapy biomarker. They stated that their methods showed correlations only and could not establish cause, and that combining data from different databases may introduce bias.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of publicly available gene-expression, mutation and survival databases (TCGA, GTEx, CCLE, HPA, cBioPortal, CIBERSORT); no new patients or experiments
• Who was studied: Tumor and normal tissue data from public databases: TCGA tumor samples (33 tumor types, including mesothelioma), GTEx normal tissue data from 31 tissues, CCLE cancer cell lines, and HPA immunohistochemistry images for six cancers. The alteration analysis used TCGA pan-cancer atlas studies covering 10,967 patients from 32 cancer types.
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was the expression level and alteration (e.g. mutation) of the NF2 gene in tumor and normal tissue.
• Main results:
  • NF2 expression differed significantly from normal tissue in 25 cancer types and was upregulated in 21 of them. It was lower in tumors in adrenocortical carcinoma, glioblastoma, kidney renal clear cell carcinoma and testicular germ cell tumors. Mesothelioma is not among the cancers listed in this tumor-versus-normal comparison.
  • In the Cox analysis of overall survival, NF2 was a low-risk factor in kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, lower grade glioma and pheochromocytoma/paraganglioma. It was a high-risk factor in the other cancers with significant associations: adrenocortical carcinoma and liver hepatocellular carcinoma.
  • In Kaplan-Meier analysis of disease-specific survival, low NF2 expression went with better survival in adrenocortical carcinoma, sarcoma and skin melanoma. The opposite pattern was seen in several cancers including mesothelioma (MESO). This result is shown in a supplementary figure not included in the text.
  • NF2 alterations were mostly mutations and were most frequent in pleural mesothelioma (22.99%), cholangiocarcinoma (5.56%) and endometrial cancer (3.75%).
  • In the ROC (diagnostic accuracy) analysis, NF2 showed high diagnostic accuracy in 4 cancer types, relative accuracy in 9 and low accuracy in 14. The highest AUC was 1.0, in cholangiocarcinoma.
  • NF2 expression was significantly higher in the early stages of 9 cancers.
  • NF2 expression was positively correlated with tumor mutational burden in 7 cancers and negatively in thyroid carcinoma and uveal melanoma. It was positively correlated with microsatellite instability in 7 tumors.
• The authors' conclusion: The authors concluded that NF2 is a promising diagnostic, prognostic and immunotherapeutic biomarker for many tumor types. They speculated that patients with high NF2 expression might benefit from immune checkpoint inhibitor therapy in certain cancers.
• Limitations the authors state:
  • Systematic biases may exist because the data came from different databases.
  • The bioinformatics methods can show correlations but cannot establish cause and effect.
  • Some patients had poor prognosis despite high NF2 expression, even though NF2 is a tumor suppressor. The authors attributed this possibly to tumor heterogeneity and complexity.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Carcinogenesis, Mesothelioma, Prognosis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI-H), checkpoint inhibitors.

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