Integrated pancancer analysis reveals the oncogene characteristics and prognostic value of DIP2B in breast cancer

Our plain-English summary of Integrated pancancer analysis reveals the oncogene characteristics and prognostic value of DIP2B in breast cancer, by C. Song, F. Shang, W. Tu, et al (BMC Cancer, 2023).

The study

• Authors: C. Song, F. Shang, W. Tu, X. Liu
• Journal: BMC Cancer
• Published: 2023;23(1):296
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Disco-interaction protein 2 homologue B (DIP2B) plays an important role in DNA methylation. There have been many reports on DIP2B in various diseases, but neither the diagnostic value nor the prognostic value of DIP2B across cancer types has been deeply explored.

Methods: The expression levels of DIP2B in 33 cancer types were analysed based on data sets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The relationships of DIP2B expression with immune cell infiltration and immune-related gene expression were studied via the CIBERSORT, ESTIMATE and TISIDB tools. Gene set variation analysis (GSVA) was performed to identify pathways related to DIP2B. DIP2B knockdown by siRNA was performed in breast cancer cell lines to investigate the effect on proliferation, apoptosis and migration. The relationships of DIP2B expression with clinicopathological features and prognosis were analysed based on immunohistochemistry.

Results: DIP2B was highly expressed in 26 of 33 cancer types and was significantly associated with poor overall survival (OS) in breast invasive carcinoma (BRCA), mesothelioma and chromophobe renal cell carcinoma (each P < 0.05). DIP2B showed a negative correlation with the immune score, the infiltration levels of key immune killer cells (CD8 + T cells, activated NK cells and plasma cells), and the expression of major histocompatibility complex-related genes and chemokine-related genes in BRCA. Subtype analysis showed that DIP2B expression was associated with poor OS in Her-2 + BRCA patients (P < 0.05). DIP2B showed a negative correlation with immune killer cell infiltration and immune regulatory genes in BRCA subtypes. In BRCA, the GSVA results revealed that genes correlating positively with DIP2B were enriched in cancer-related pathways (PI3K-AKT) and cell-cycle-related pathways (MITOTIC_SPINDLE, G2M_CHECKPOINT and E2F_TARGETS), while genes correlating negatively with DIP2B were enriched in DNA_REPAIR. Knockdown of the DIP2B gene induced a reduction in proliferation and migration and an increase in apoptosis in breast cancer cell lines. DIP2B expression was associated with lymph node metastasis and poor histological grade in BRCA according to immunohistochemistry (each P < 0.05). DIP2B expression predicted reduced disease-free survival and OS in BRCA patients (each P < 0.05), especially those with the Her-2 + subtype (P = 0.023 and P = 0.069).

Conclusions: DIP2B may be a prognostic biomarker for BRCA, especially for the Her-2 + subtype. DIP2B is associated with a "cold" tumour immune microenvironment in BRCA and might serve as a future target for immunotherapy.

© 2023. The Author(s).

In plain English

This study examined a gene called DIP2B, mainly in breast cancer. It did not study asbestos. Using public gene databases covering 33 cancer types, the authors found DIP2B was more highly expressed than in normal tissue in 26 types. By two survival methods, higher DIP2B expression was associated with poorer overall survival in three cancers: breast invasive carcinoma, kidney chromophobe and mesothelioma. The article does not say whether the mesothelioma was pleural or peritoneal. In mesothelioma, DIP2B showed no significant relationship with tumour immune score or with two groups of immune-related genes, and a negative association with some immune killer cells. Reducing DIP2B in four breast cancer cell lines lowered cell growth and migration and raised apoptosis (programmed cell death). In tissue from 120 breast cancer patients treated in Shenyang, China, 47 of 120 samples showed high DIP2B, which was associated with lymph node metastasis and higher histological grade. The authors concluded DIP2B might be considered an oncogene and used as a prognostic biomarker in breast cancer.

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 public gene-expression databases (TCGA, GTEx, CCLE), plus laboratory experiments in breast cancer cell lines and a retrospective immunohistochemistry study of breast cancer tissue
• Who was studied: Database samples from 33 cancer types (one of them mesothelioma) compared with normal tissues; four human breast cancer cell lines (MCF-7, T47D, SK-BR-3, MDA-MB-231); and tissue from 120 breast cancer patients who had radical surgery at the Fourth Affiliated Hospital of China Medical University, Shenyang, China, January 2008 to December 2012
• Exposure: No asbestos or other environmental exposure was studied. The factor examined was expression of the DIP2B gene. No fiber type, product, job or dose is given.
• Main results:
  • In the database analysis, DIP2B was highly expressed in 26 of 33 cancer types compared with normal tissues
  • By both Cox and Kaplan-Meier analysis, DIP2B expression was associated with poor overall survival in breast invasive carcinoma (BRCA), kidney chromophobe (KICH) and mesothelioma (MESO), each P less than 0.05
  • In mesothelioma and kidney chromophobe, no significant relationship was found between DIP2B and tumour purity or immune score
  • DIP2B showed a negative association with most immune killer cells in breast cancer and with some immune killer cells in mesothelioma
  • DIP2B expression did not affect MHC-related or chemokine-related gene expression in mesothelioma. In breast cancer it showed a significant negative correlation with these genes.
  • Reducing DIP2B with siRNA lowered proliferation in four breast cancer cell lines compared with the blank control group (each P less than 0.05)
  • In breast cancer cells, reducing DIP2B raised the apoptosis rate compared with the blank control group
  • In breast cancer cells, reducing DIP2B lowered wound closure (migration) compared with the blank control group
  • In the 120-patient breast cancer cohort, 39.2% (47/120) of samples showed high DIP2B expression
  • High DIP2B protein was associated with high histological grade and lymph node metastasis (Table 1: P = 0.004 for grade, P = 0.040 for lymph node metastasis)
  • In the breast cancer cohort, Kaplan-Meier analysis linked DIP2B expression, along with T stage, N stage, TNM stage, molecular subtype and histological grade, to disease-free survival and overall survival (each P less than 0.05)
  • Table 2 prints, for high DIP2B expression with low expression as reference, a disease-free survival hazard ratio of 0.441 (95% CI 0.228 to 0.853, P = 0.015) and an overall survival hazard ratio of 0.404 (95% CI 0.172 to 0.947, P = 0.037). See text problems about the direction of these figures.
  • In Her-2+ breast cancer patients, high DIP2B predicted significantly reduced disease-free survival (P = 0.023)
  • In Her-2+ breast cancer patients, high DIP2B showed only a tendency towards poor overall survival (P = 0.069)
• The authors' conclusion: The authors concluded that DIP2B might be considered an oncogene and used as a prognostic biomarker in breast cancer. They also concluded that its expression predicts a 'cold' tumour microenvironment and that it might be a potential target to improve the response to immunotherapy in breast cancer.
• Limitations the authors state:
  • Potential bias from the nature of bioinformatics analysis
  • Potential bias from an insufficient clinical sample size, especially in the breast cancer subtype analysis
  • No data from living-animal (in vivo) models
  • The specific mechanisms of DIP2B in breast cancer need further investigation

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Prognosis, Immunohistochemistry, Overall Survival, Carcinoma, Mesothelioma, Metastasis, Disease-Free Survival.

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