scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

scholarly journals Upregulation of FGD6 Predicts Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianmin Zeng ◽  
Man Li ◽  
Huasheng Shi ◽  
Jianhui Guo
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Cox Regression Analysis ◽  
The Relationship

Background: The aim of this study was to investigate the prognostic significance of faciogenital dysplasia 6 (FGD6) in gastric cancer (GC).Methods: The data of GC patients from The Cancer Genome Atlas (TCGA) database were used for the primary study. Then, our data were validated by the GEO database and RuiJin cohort. The relationship between the FGD6 level and various clinicopathological features was analyzed by logistic regression and univariate Cox regression. Multivariate Cox regression analysis was used to evaluate whether FGD6 was an independent prognostic factor for survival of patients with GC. The relationship between FGD6 and overall survival time was explored by the Kaplan–Meier method. In addition, gene set enrichment analysis (GSEA) was performed to investigate the possible biological processes of FGD6.Results: The FGD6 level was significantly overexpressed in GC tissues, compared with adjacent normal tissues. The high expression of FGD6 was related to a high histological grade, stage, and T classification and poor prognosis of GC. Multivariate Cox regression analysis showed that FGD6 was an independent prognostic factor for survival of patients with GC. GSEA identified that the high expression of FGD6 was mainly enriched in regulation of actin cytoskeleton.Conclusion: FGD6 may be a prognostic biomarker for predicting the outcome of patients with GC.

KIAA0101 in Malignant Pleural Mesothelioma: a Potential Diagnostic and Prognostic Marker

2021 ◽  
Vol 24 ◽  
Author(s):  
Ping Lin ◽  
Yuean Zhao ◽  
Xiaoqian Li ◽  
Zongan Liang
Keyword(s):  
Gene Expression ◽  
Regression Analysis ◽  
Malignant Pleural Mesothelioma ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Pleural Mesothelioma ◽  
Hub Genes ◽  
Cox Regression Analysis

Background: Currently, there are no reliable diagnostic and prognostic markers for malignant pleural mesothelioma (MPM). The objective of this study was to identify hub genes that could be helpful for diagnosis and prognosis in MPM by using bioinformatics analysis. Materials and Methods: The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA), LASSO regression analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) were performed to identify hub genes and their functions. Results: A total of 430 up-regulated and 867 downregulated genes in MPM were identified based on the GSE51024 dataset. According to the WGCNA analysis, differentially expressed genes were classified into 8 modules. Among them, the pink module was most closely associated with MPM. According to genes with GS > 0.8 and MM > 0.8, six genes were selected as candidate hub genes (NUSAP1, TOP2A, PLOD2, BUB1B, UHRF1, KIAA0101) in the pink module. In the LASSO model, three genes (NUSAP1, PLOD2, and KIAA0101) were identified with non-zero regression coefficients and were considered hub genes among the 6 candidates. The hub gene-based LASSO model can accurately distinguish MPM from controls (AUC = 0.98). Moreover, the high expression level of KIAA0101, PLOD2, and NUSAP1 were all associated with poor prognosis compared to the low level in Kaplan–Meier survival analyses. After further multivariate Cox analysis, only KIAA0101 (HR = 1.55, 95% CI = 1.05-2.29) was identified as an independent prognostic factor among these hub genes. Finally, GSEA revealed that high expression of KIAA0101 was closely associated with 10 signaling pathways. Conclusion: Our study identified several hub genes relevant to MPM, including NUSAP1, PLOD2, and KIAA0101. Among these genes, KIAA0101 appears to be a useful diagnostic and prognostic biomarker for MPM, which may provide new clues for MPM diagnosis and therapy.

scholarly journals High Expression of PABPC1 Predicts Worse Survival of Gastric Cancer Patients

2020 ◽  
Author(s):  
Tailai An ◽  
Lingna Deng ◽  
Zheng Yang ◽  
Cuicui Chai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Mrna Translation ◽  
High Expression ◽  
Depth Of Invasion ◽  
Cox Regression Analysis

Abstract Background: Gastric cancer (GC) is one of the most common cancers with one of the highest mortality rates. Unfortunately, underlying molecular mechanisms contributing to GC have not been fully illuminated. PABPC1 is involved in a series of processes, such as mRNA translation, and mRNA deadenylation and decay. We performed this study to clarify the role of PABPC1 in GC. Methods: To evaluate PABPC1 expressions in GC and normal tissues, we performed bioinformatics analysis of data from TCGA. PABPC1 expressions were evaluated by immunohistochemical (IHC) staining of 170 GC specimens. Associations between PABPC1 expression and clinicopathological variables were analyzed. Independent predictive factors for survival of GC patients were determined by Cox regression analysis. Results: It was revealed by bioinformatics analysis that compared with normal gastric tissues, PABPC1 expressions in GC tissues were significantly higher (P=0.002, paired) (P=3.605e^-9, unpaired). It was revealed that PABPC1 expression was significantly associated with tumor size (P=0.008), Borrmann classification (P=0.003), vessel invasion (P=0.017), depth of invasion (P=0.032), lymph node metastasis (P=0.001), and TNM stage (P=0.019). It was demonstrated through Cox regression analysis that PABPC1 expression was a predictive factor for both overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) of GC patients. Conclusions: Compared with that of normal gastric tissue, expression level of PABPC1 in GC tissue was significantly higher and PABPC1,s high expression was significantly associated with poorer survival, suggesting its potential as a therapeutic biomarker for GC.

scholarly journals Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Song Wang ◽  
Xueyou Ma ◽  
Yufan Ying ◽  
Jiazhu Sun ◽  
Zitong Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Wound Healing ◽  
Regression Analysis ◽  
Cell Lines ◽  
Cox Regression ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
High Expression Level

Abstract Background Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity. Methods The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan–Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME). Results ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. Conclusion ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.

scholarly journals SCUBE3 serves as an independent poor prognostic factor in breast cancer

2021 ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in age, histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95 % CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95 % CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

scholarly journals Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Enxin Zhang ◽  
Haifu Huang ◽  
Ying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Rapid Progression ◽  
Raw Data ◽  
Cox Regression Analysis ◽  
Free Interval

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with rapid progression, high recurrence rate and poor prognosis. The objective of our investigation was to explore the prognostic value of CDK5R1 in HCC. Methods: The raw data of HCC raw data were downloaded from The Cancer Genome Atlas (TCGA) database. The Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to investigate the relevance between the CDK5R1 expression and clinicopathologic characteristics in HCC. Kaplan-Meier and Cox regression analysis were employed to examine the association between clinicopathologic features and survival. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of CDK5R1. Results: CDK5R1 was highly expressed in HCC tissues. The high expression of CDK5R1 in HCC tissues was significantly associated with tumor status (P=0.00), new tumor event (P=0.00), clinical stage (P=0.00), topography (P=0.00). Elevated CDK5R1 had significant correlation with worse overall survival (OS) (P=7.414e−04), disease-specific survival (DSS) (P=5.642e−04), disease-free interval (DFI) (P=1.785e−05), and progression-free interval (PFI) (P=2.512e−06). Besides, univariate and multivariate Cox regression analysis uncovered that increased CDK5R1 can independently predict adverse OS (P=0.037, hazard ratio [HR]=1.7 (95% CI [1.0-2.7])), DFI (P=0.007, hazard ratio [HR]=3.0 (95% CI [1.4-6.7])), PFI (P=0.007, hazard ratio [HR]=2.8 (95% CI [1.3-5.9])). GSEA disclosed that notch signaling pathway and non-small cell lung cancer were prominently enriched in CDK5R1 high expression phenotype. Conclusions: Increased CDK5R1 may act as a promising independent prognostic factor of poor survival in HCC.

scholarly journals Construction and Validation of a Reliable Six-Gene Prognostic Signature Based on the TP53 Alteration for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Signature ◽  
Gene Set Enrichment ◽  
Cox Regression Analysis ◽  
Gene Set

BackgroundThe high mutation rate of TP53 in hepatocellular carcinoma (HCC) makes it an attractive potential therapeutic target. However, the mechanism by which TP53 mutation affects the prognosis of HCC is not fully understood.Material and ApproachThis study downloaded a gene expression profile and clinical-related information from The Cancer Genome Atlas (TCGA) database and the international genome consortium (ICGC) database. We used Gene Set Enrichment Analysis (GSEA) to determine the difference in gene expression patterns between HCC samples with wild-type TP53 (n=258) and mutant TP53 (n=116) in the TCGA cohort. We screened prognosis-related genes by univariate Cox regression analysis and Kaplan–Meier (KM) survival analysis. We constructed a six-gene prognostic signature in the TCGA training group (n=184) by Lasso and multivariate Cox regression analysis. To assess the predictive capability and applicability of the signature in HCC, we conducted internal validation, external validation, integrated analysis and subgroup analysis.ResultsA prognostic signature consisting of six genes (EIF2S1, SEC61A1, CDC42EP2, SRM, GRM8, and TBCD) showed good performance in predicting the prognosis of HCC. The area under the curve (AUC) values of the ROC curve of 1-, 2-, and 3-year survival of the model were all greater than 0.7 in each independent cohort (internal testing cohort, n = 181; TCGA cohort, n = 365; ICGC cohort, n = 229; whole cohort, n = 594; subgroup, n = 9). Importantly, by gene set variation analysis (GSVA) and the single sample gene set enrichment analysis (ssGSEA) method, we found three possible causes that may lead to poor prognosis of HCC: high proliferative activity, low metabolic activity and immunosuppression.ConclusionOur study provides a reliable method for the prognostic risk assessment of HCC and has great potential for clinical transformation.

scholarly journals SCUBE3 Serves as an Independent Poor Prognostic Factor in Breast Cancer

2020 ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Expression Levels

Abstract Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by univariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. SCUBE3 expression was significantly correlated with ER (p = 0.018), PR (p = 0.015), HER2 (p = 0.039), and triple-negative status (p = 0.049) of patients with breast cancer. We further verified that the expression levels of SCUBE3 mRNA was significantly correlated with ER (p = 0.0007), PR (p = 0.0295), and triple-negative (p = 0.0024), respectively. There was no significant expression difference in the expression of SCUBE3 mRNA in age, HER2 receptor status, and nodal status (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The univariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

scholarly journals An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jingsun Wei ◽  
Xiaoxu Ge ◽  
Yang Tang ◽  
Yucheng Qian ◽  
Wei Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Analysis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose. Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. Methods. In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. Results. The high-risk group’s overall survival time was significantly shorter than that of the low-risk group p < 0.0001 . Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. Conclusion. The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.

scholarly journals SCUBE3 serves as an independent poor prognostic factor in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Xi He ◽  
Zhenwei Li ◽  
Fan Yang ◽  
Shengnan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Functional Enrichment ◽  
High Expression ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Background Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein–protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20–6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06–3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. Conclusions These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

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