scholarly journals Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Wei-xian Chen ◽  
Liang-gen Yang ◽  
Ling-yun Xu ◽  
Lin Cheng ◽  
Qi Qian ◽  
...  

Abstract Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods:RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results:RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Wei-xian Chen ◽  
Lin Cheng ◽  
Ling-yun Xu ◽  
Qi Qian ◽  
Yu-lan Zhu

Abstract Background: Tripartite motif 13 (TRIM13) plays a significant role in various biological processes including cell growth, apoptosis, transcriptional regulation, and carcinogenesis. However, the prognostic significance of TRIM13 gene in breast cancer treatment remains largely unclear. Methods: We performed a bioinformatics analysis of the clinical parameters and survival data as it relates to TRIM13 in breast cancer patients using several online databases including Oncomine, bcGenExMiner, PrognoScan, and UCSC Xena. Results: We found that TRIM13 was lower-expressed in different subtypes of breast cancer with respect to normal tissues. Estrogen receptor and progesterone receptor status were positively correlated with TRIM13 level; whereas, the Scarff–Bloom–Richardson grade, Nottingham prognostic index, nodal status, basal-like status, and triple-negative status were negatively related to TRIM13 expression in breast cancer patients with respect to normal individuals. Lower TRIM13 expression correlated with worse distant metastasis free survival, relapse free survival, disease specific survival, and metastatic relapse free survival. We also confirmed a positive correlation between TRIM13 and RAB11FIP2 gene expression. Conclusion: Bioinformatics analysis revealed that TRIM13 may be adopted as a promising predictive biomarker for prognosis of breast cancer. More in-depth experiments and clinical trials are needed to validate the value of TRIM13 in breast cancer treatment.


2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Mingdi Zhang ◽  
Hongliang Chen ◽  
Maoli Wang ◽  
Fang Bai ◽  
Kejin Wu

Abstract Background: Collagen type X alpha 1 (COL10A1) is overexpressed in diverse tumors and displays vital roles in tumorigenesis. However, the prognostic value of COL10A1 in breast cancer remains unclear. Methods: The expression of COL10A1 was analyzed by the Oncomine database and UALCAN cancer database. The relationship between COL10A1 expression level and clinical indicators including prognostic data in breast cancer were analyzed by the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results: COL10A1 was up-regulated in different subtypes of breast cancer. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) status and nodal status were positively correlated with COL10A1 expression. Conversely, age, the Scarff–Bloom–Richardson (SBR) grade, basal-like status, and triple-negative status were negatively related to COL10A1 level in breast cancer samples compared with normal tissues. Patients with increased COL10A1 expression level showed worse overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). COL10A1 was positively correlated with metastatic relapse-free survival. GSEA analysis revealed that enrichment of TGF-β signaling pathway. 15-leucine-rich repeat containing membrane protein (LRRC15) is a correlated gene of COL10A1. Conclusion: Bioinformatics analysis revealed that COL10A1 might be considered as a predictive biomarker for prognosis of breast cancer. Further experiments and clinical trials are essential to elucidate the value of COL10A1 in breast cancer treatment.


2002 ◽  
Vol 20 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
Roman Rouzier ◽  
Jean-Marc Extra ◽  
Jerzy Klijanienko ◽  
Marie-Christine Falcou ◽  
Bernard Asselain ◽  
...  

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 567-567
Author(s):  
S. Braun ◽  
F. D. Vogl ◽  
K. Pantel

567 Background: As a putative surrogate marker of ubiquitous distant metastasis, which is assessable both at initial diagnosis of breast cancer and during adjuvant therapy, BMM would be a valuable end-point marker for adjuvant clinical trials. Methods: Based on individual pt data of 4,686 breast cancer pts with a 10-year follow-up (median, 62 months), we analyzed distant disease-free survival (DDFS) of BMM+/BMM− pts, and looked specifically into sites of first metastatic relapse, expressed as bone metastasis-free (BFS), visceral metastasis-free (VFS), and multiple metastasis-free survival (MFS; i.e., simultaneous diagnosis of bone and visceral metastases). We performed Kaplan-Meier analysis and computed incidence rates (IR)/ incidence rate ratios (IRR) for the occurrence of metastasis at different sites. Results: BMM were detected in 1,432 (30.6%) of pts overall and significantly more often in pts with subsequent diagnosis of distant metastasis as compared to those who survived without metastases (48.5% vs. 26.0%, P<0.001). BMM+ pts had a significantly shorter DDFS than BMM- pts (IRR 2.36; 95%CI, 2.07–2.69; P<0.001). This was also true when we analyzed either bone (IRR 2.73; 95%CI, 2.27–3.29; P<0.001) or visceral metastases only (IRR, 2.48; 95%CI, 2.11–2.91; P<0.001). Among 952 pts with occurrence of distant metastasis, IR of such an event was 1.28-fold (95%CI, 1.12–1.46; P<0.001) higher in BMM+ pts than in BMM- pts. Among 462 BMM+ pts (but not among those 490 BMM- pts), IRs for MFS were significantly increased as compared to both VFS (IRR 1.72; 95%CI, 1.36–2.18; P<0.001) and BFS (IRR 1.85; 95%CI 1.21–2.06; P=0.001). IR for BFS of BMM+ patients (1.08; 95%CI 0.87–1.34) was not significantly increased over VFS. Conclusion: Our data provide conclusive evidence that presence of BMM predicts an early onset and a poor prognosis pattern of overt distant metastasis. With the similar likelihood of the occurrence of subsequent metastasis in bone and at visceral sites, BMM appears to be a marker of generalized tumor cell spread. No significant financial relationships to disclose.


2006 ◽  
Vol 12 (22) ◽  
pp. 6696-6701 ◽  
Author(s):  
Patrizia Querzoli ◽  
Massimo Pedriali ◽  
Rosa Rinaldi ◽  
Anna Rita Lombardi ◽  
Elia Biganzoli ◽  
...  

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Jian-bo Dai ◽  
Bei Zhu ◽  
Wei-jia Lin ◽  
Hai-yan Gao ◽  
Hong Dai ◽  
...  

Abstract Aims: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer. Methods: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan–Meier Plotter. BIRC5–drug interaction network was obtained using the Comparative Toxicogenomics Database. Results: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff–Bloom–Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5–drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed. Conclusion: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Qiaoyun Wang ◽  
Shuai Zhao ◽  
Lei Gan ◽  
Zhixiang Zhuang

Abstract Background: Paired-like homeodomain transcription factor 1 (PITX1) participates in miscellaneous biological processes including cell growth, development, progression and invasion in various malignant tumors. However, the analysis of the association between PITX1 expression and the survival in breast cancer remains unclear. Methods: Clinical prognostic parameters and survival data related to PITX1 in breast cancer patients were performed using the bioinformatic analysis including Oncomine, Bc-GenExMiner v4.3, PrognoScan and UCSC Xena. Results: We found that PITX1 gene expression was significantly higher in different histological classification of breast cancer. The Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), estrogen receptor (ER) negative, epidermal growth factor receptor-2 (HER2) positive, lymph node positive, triple-negative status and basal-like status were positively correlated with PITX1 level, except for patients’ age and the progesterone receptor (PR) status. We have found that the increased PITX1 expression correlated with worse relapse-free survival, disease specific survival and overall survival. PITX1 was positively correlated with metastatic relapse-free survival and distant metastasis-free survival. We also confirmed positive correlation between PITX1 and the nucleotide-binding oligomerization domain 2 (NOD2). Conclusion: The lower expression of PITX1 was associated with better clinical prognostic parameters and clinical survival in breast cancer according to the bioinformatic analysis.


2020 ◽  
Author(s):  
Arooj Shafiq ◽  
January Moore ◽  
Aliya Suleman ◽  
Sabeen Faiz ◽  
Omar Farooq ◽  
...  

ABSTRACTPurposeGalectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3.MethodsBreast cancer patients with first time cancer diagnosis and no prior treatment (n=88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA respectively. Healthy women (>18 years of age, n=63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease free survival analysis.ResultsEnhanced levels of plasma (adjuvant) and stromal (neo-adjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion.ConclusionThe findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors post chemotherapy can also be used to predict long term prognosis in patients.Key pointsIncreased Gal-3 secretion due to chemotherapy leads to better prognosis and longer disease-free survival.The analysis of soluble Gal-3 expression could be useful as a support tool in predicting treatment efficacy in patients with no visible tumor remaining for follow up through imaging.


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