Dataset Information

Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.

ABSTRACT: DNA double-strand break (DSB) repaired by homologous recombination (HR) is an essential process for breast cancer cells to survive. DNA2 nuclease acts parallel to homologous recombination (HR). Here, we investigated the detailed clinical attribute of DNA2 in breast cancer and the role of DNA2 in breast cancer cells' growth. We found that elevated expression of DNA2 was obviously linked to poor prognosis in breast cancer. Further, DNA2 expression was increased in the ER-negative group, PR-negative group, HER2-positive group, and high-grade group via analyzing 2,509 breast cancers in "cBioportal" and 3,063 breast cancer data in "bc-GenExMiner." Besides, the immunohistochemical staining in 26 breast cancer tissues also showed that elevated expression of DNA2 was correlated with ER-/PR-/HER+. To further detect the role of DNA2 in breast cancer cells, we took GESA, GO, and KEGG analyses and found that DNA2 was enriched in cell cycle and DNA replication pathways. Furthermore, silencing of DNA2 inhibited cell growth in T47D and MD-MB-231 breast cancer cells and suppressed tumor growth in vivo, indicating DNA2 functioned importantly in breast cancer progression and maybe a potential prognostic marker in breast cancer. Our research reveals that DNA2 is a biomarker for diagnosis and prognosis in breast cancer from multiple perspectives and gives a new clue for further preclinical and clinical investigation.

SUBMITTER: Han Y

PROVIDER: S-EPMC7857872 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.

Han Yingyan Y Zhang Zeyu Z Wang Zhi Z Sun Shujuan S

Disease markers 20210126

DNA double-strand break (DSB) repaired by homologous recombination (HR) is an essential process for breast cancer cells to survive. DNA2 nuclease acts parallel to homologous recombination (HR). Here, we investigated the detailed clinical attribute of DNA2 in breast cancer and the role of DNA2 in breast cancer cells' growth. We found that elevated expression of DNA2 was obviously linked to poor prognosis in breast cancer. Further, DNA2 expression was increased in the ER-negative group, PR-negativ ...[more]

PMID: 33574966

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Project description:Overexpression of synaptonemal complex protein-2 (SYCP2) has been identified in various human papillomavirus (HPV)-related carcinomas, whereas its significant role in breast carcinoma remains unclear. The aim of this study was to elucidate the prognostic value and potential function of SYCP2 in breast carcinoma. Herein, data for breast carcinoma patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database (TCGA) were analyzed. The enrichment analysis of SYCP2 including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Friends, and GSEA was performed. Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves were employed for determining the predictive value of SYCP2 on clinical outcomes in patients suffering from breast carcinoma. A nomogram was generated to predict the effect arising from SYCP2 on prognosis. The association analysis of SYCP2 gene expression and diverse immune infiltration levels was conducted through ssGSEA and ESTIMATE analysis, which consisted of dendritic cell (DC), neutrophil, eosinophil, macrophage, mast cell, NK cell, and other 18 cell subtypes. The results showed that SYCP2 expression was significantly elevated in breast carcinoma tissues as compared with that of normal tissues (p < 0.001). SYCP2 plays a certain role in pathways related to DNA methylation, keratinocyte differentiation, steroid hormone biosynthesis, and immune infiltration. The high expression of SYCP2 had a significant relationship to age, pathological type, ER expression, and PR expression (p < 0.001). Kaplan-Meier survival analysis showed that patients suffering from breast carcinoma characterized by high-SYCP2 expression had a poorer prognosis than patients with low-SYCP2 expression (p = 0.005). Univariate and multivariate Cox regression analyses revealed that SYCP2 had an independent relationship to overall survival (p = 0.049). Moreover, ROC curves suggested the significant diagnostic ability of SYCP2 for breast carcinoma, and as time went on, SYCP2 had more accurate prognostic efficacy. Furthermore, a high level of SYCP2 expression was found to have a relationship to poor prognosis of breast carcinoma in the subgroups of T3, N0, and M0, and infiltrating ductal carcinoma (HR > 1, p < 0.05). The calibration plot of the nomogram indicated that the SYCP2 model has an effective predictive performance for breast carcinoma patients. Conclusively, SYCP2 plays a vital role in the pathogenesis and progression of human breast carcinoma, so it may serve as a promising prognostic molecular marker of poor survival.

Project description:Background: Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis. Methods: IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as by our clinical gastric specimens. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database. Results: IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the mRNA level of IGFBP7 was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs). Conclusions: Increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC, which might be a potential biomarker for the diagnosis of GC.

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Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.

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Increased Expression of DNA2 Was Linked to Poor Prognosis in Breast Cancer.

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