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Loss of SUSD2 expression correlates with poor prognosis in patients with surgically resected lung adenocarcinoma.

ABSTRACT: There is limited evidence regarding the relationship between the expression of Sushi Domain Containing 2 (SUSD2) and prognosis of patients with surgically resected lung adenocarcinoma (LUAD). This retrospective study aimed to investigate the clinical significance of SUSD2 expression in LUAD. To assess SUSD2 expression in LUAD, we conducted both integrated bioinformatic analysis based on the TCGA database and also immunohistochemistry study using a tissue microarray encompassing 578 LUAD cases from our hospital. Reduced SUSD2 expression was associated with gender, smoking history, higher pathological grade, lymph node metastasis, larger tumor length, advanced TNM stage. LUAD patients with SUSD2-positive tumors showed significantly better overall survival (OS) than those with SUSD2-negative tumors (P = 0.000). When patients were stratified into those with stage I (218, 37.7%), II (152, 26.3%) and III (208, 36.0%) disease, and those without (254, 43.9%) and with (324, 56.1%) lymph node metastasis, the prognostic effect was almost consistent. The OS of patients with positive SUSD2 expression was significantly better in patients with stage I (P = 0.000), III (P = 0.000), without (P = 0.000) and with (P = 0.001) lymph node metastasis. Multivariate analysis showed that loss of SUSD2 predicted a shorter survival time and was an independent prognostic factor for LUAD patients. Our study indicated that SUSD2 may serve as a new prognostic and potential therapeutic target in LUAD.

SUBMITTER: Guo W

PROVIDER: S-EPMC7052850 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Loss of SUSD2 expression correlates with poor prognosis in patients with surgically resected lung adenocarcinoma.

Guo Wei W Shao Fei F Sun Sijin S Song Peng P Guo Lei L Xue Xuemin X Zhang Guochao G Zhang Hao H Gao Yibo Y Qiu Bin B Tan Fengwei F Gao Shugeng S He Jie J

Journal of Cancer 20200114 7

There is limited evidence regarding the relationship between the expression of Sushi Domain Containing 2 (SUSD2) and prognosis of patients with surgically resected lung adenocarcinoma (LUAD). This retrospective study aimed to investigate the clinical significance of SUSD2 expression in LUAD. To assess SUSD2 expression in LUAD, we conducted both integrated bioinformatic analysis based on the TCGA database and also immunohistochemistry study using a tissue microarray encompassing 578 LUAD cases fr ...[more]

PMID: 32194777

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Project description:BackgroundLung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein "reader" of N6-methyladenosine (m6A) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.MethodsThe Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).ResultsFive data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging (P < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) (P < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts (P < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.ConclusionsHigh HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.

Project description:Background: Lung cancer has the highest morbidity and mortality of cancers worldwide. Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer and surgery is its most common treatment. The dysregulated expression of DNA repair genes is found in a variety of cancers and has been shown to affect the origin and progression of these diseases. However, the function of DNA repair genes in surgically-treated LUAD is unclear.Methods: We sought to determine the association between the signature of DNA repair genes for patients with surgical LUAD and their overall prognosis. We obtained gene expression data and corresponding clinical information of LUAD from The Cancer Genome Atlas (TCGA) database. The differently expressed DNA repair genes of surgically-treated LUAD and normal tissues were identified using the Wilcoxon rank-sum test. We used uni- and multivariate Cox regression analyses to shrink the aberrantly expressed genes, which were then used to construct the prognostic signature and the risk score formula associated with the independent prognosis of surgically-treated LUAD. We used Kaplan-Meier and Cox hazard ratio analyses to confirm the diagnostic and prognostic roles. Two validation sets (GSE31210 and GSE37745) were downloaded from the Gene Expression Omnibus (GEO) and were used to externally verify the prognostic value of the signature. OSluca online database verifies the hazard ratio for the DNA repair genes by which the signature was constructed. We investigated the correlation between the signature of the DNA repair genes and the clinical parameters. The potential molecular mechanisms and pathways of the prognostic signature were explored using Gene Set Enrichment Analysis (GSEA).Results: We determined the prognostic signature based on six DNA repair genes (PLK1, FOXM1, PTTG1, CCNO, HIST3H2A, and BLM) and calculated the risk score based on this formula. Patients with surgically-treated LUAD were divided into high-risk and low-risk groups according to the median risk score. The high-risk group showed poorer overall survival than the low-risk group; the signature was used as an independent prognostic indicator and had a greater prognostic value in surgically-treated LUAD. The prognostic value was replicated in GSE31210 and GSE37745. OSluca online database analysis shows that six DNA repair genes were associated with poor prognosis in most lung cancer datasets. The prognostic signature risk score correlated with the pathological stage and smoking status in surgically-treated LUAD. The GSEA of the risk signature in high-risk patients showed pathways associated with the cell cycle, oocyte meiosis, mismatch repair, homologous recombination, and nucleotide excision repair.Conclusions: A six-DNA repair gene signature was determined using TCGA data mining and GEO data verification. The gene signature may serve as a novel prognostic biomarker and therapeutic target for surgically-treated LUAD.

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Loss of SUSD2 expression correlates with poor prognosis in patients with surgically resected lung adenocarcinoma.

Publications

Loss of SUSD2 expression correlates with poor prognosis in patients with surgically resected lung adenocarcinoma.

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