scholarly journals LSM3, NDUFB3, and PTGS2 may be potential biomarkers for BRCA1-mutation positive breast cancer

2020 ◽  
Vol 28 (4) ◽  
pp. 381-391
Author(s):  
Kang Hu ◽  
Fengjiao Gan ◽  
Xue Wang ◽  
Lin Xu ◽  
Qiaoyuan Wu ◽  
...  

AbstractPurpose: We aimed to find critical biomakers associated with BRCA1-mutation positive breast cancer.Methods: The data set E-MTAB-982 was downloaded from ArrayExpress database and the data were preprocessed using R package Oligo. Differential expression analysis between BRCA1-mutation positive breast cancer patients and BRCA1-mutation positive healthy subjects were performed using limma package. Then, gene set enrichment analysis was conducted. We constructed the network for BRCA1, its related differentially expressed genes (DEGs), and the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. After that, survival analysis was performed based on the clinical data of breast cancer in TCGA database. Finally, box diagram for key genes was drawn.Results: The network showed that LSM3, NDUFB3, GNPDA2, and PTGS2 were BRCA1 related DEGs. Furthermore, LSM3 was mainly enriched in RNA degradation pathway and spliceosome pathway. PTGS2 was enriched in arachidonic acid metabolism and VEGF signaling pathway. Survival analysis indicated that high expression of LSM3 indicated a poor prognosis of BRCA1-mutant breast cancer. Besides, box diagram showed that LSM3 was down-regulated in BRCA1-mutation positive breast cancer patients compared with that in BRCA1-mutation positive healthy subjects.Conclusions: LSM3, NDUFB3, and PTGS2 may be biomarkers in BRCA1-mutant breast cancer, and high expression of LSM3 may indicate a poor prognosis of BRCA1-mutant breast cancer.

2021 ◽  
Vol 11 ◽  
Author(s):  
Huikun Zhang ◽  
Yawen Zhao ◽  
Xiaoli Liu ◽  
Li Fu ◽  
Feng Gu ◽  
...  

BackgroundBreast cancer is the most commonly diagnosed cancer worldwide. However, the well-known biomarkers are not enough to meet the needs of precision medicine. Novel targets are desirable and highly valuable for improved patient survival. In this regard, we identified complement component C7 as one of the candidates based on data from the OCOMINE database.MethodsC7 expression was examined by immunohistochemistry in 331 cases of invasive ductal carcinoma (IDC), 45 cases of ductal carcinoma in situ (DCIS), and 52 cases of non-neoplastic tissues adjacent to tumor. Then, C7 expression was further confirmed by Western blot analysis based on IDC specimens and non-neoplastic breast specimens. The relationship between the C7 expression and prognosis of breast cancer patients was analyzed in order to investigate the function of C7 in breast cancer patients. Meanwhile, we also analyzed the relationship between the C7 expression and prognosis of 149 patients treated with conventional TE (taxane and anthracycline)-based chemotherapy. Then, a cohort of patients (22 cases) treated with TE neoadjuvant chemotherapy was used to further confirm the relationship between the C7 expression and TE-based chemosensitivity.ResultsIn our present study, we reported for the first time that C7 was an independent prognostic factor of breast cancer and C7 expression of IDC tissues was higher than non-neoplastic tissues adjacent to tumor and DCIS. In a cohort of 331 IDC patients, high expression of C7 indicated poor prognosis especially in the triple negative subtype and luminal B subtype. Furthermore, C7 was also a promoting factor for triple negative subtype patients to develop bone metastasis. Meanwhile, we provided the first evidence that patients with high C7 expression were insensitive to TE (taxane and anthracycline)-based chemotherapy by analyzing a cohort of 149 patients treated with TE-based chemotherapy and another cohort of 22 patients treated with TE neoadjuvant chemotherapy.ConclusionsIn summary, high expression of C7 may promote breast cancer development and might be insensitive to TE-based chemotherapy. Our present study laid a foundation to help clinicians improve the identification of patients for TE-based chemotherapy by C7 in the era of precision medicine.


2001 ◽  
Vol 19 (3) ◽  
pp. 602-611 ◽  
Author(s):  

PURPOSE: To determine the influence of the epirubicin dose in operable node-positive breast cancer patients with factors of poor prognosis. PATIENTS AND METHODS: Between April 1990 and July 1993, 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade ≥ 2 and hormone receptor negativity were randomized after surgery to receive either fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days for six cycles (FEC 50) or the same regimen except with epirubicin dose of 100 mg/m2 (FEC 100). Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemotherapy. Radiotherapy was delivered at the end of chemotherapy in both groups. RESULTS: The median follow-up was 67 months. The 5-year disease-free survival (DFS) was 54.8% with FEC 50 and 66.3% with FEC 100 (P = .03). The 5-year overall survival (OS) was 65.3% and 77.4%, respectively (P = .007). The mean relative dose-intensity was similar in the two groups (90.3% and 86.1%, respectively). Neutropenia and anemia were significantly more frequent in FEC 100 (P < 10−3), as were nausea-vomiting (P = .008) and stomatitis and alopecia (P < 10−3). Nine cases of grade 3 infection occurred only with FEC 100, and no toxic deaths occurred. Three cases of acute cardiac toxicity were observed (FEC50 = 1, FEC100 = 2) and 10 patients (FEC50 = 6, FEC100 = 4) presented delayed cardiac dysfunctions. Two cases of secondary leukemia were observed (acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100). CONCLUSION: After 5 years of follow-up, the increased epirubicin dose led to a significant benefit in terms of DFS and OS, with a high survival rate among patients with poor-prognosis breast cancer.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 551-551 ◽  
Author(s):  
Jisun Kim ◽  
Wonshik Han ◽  
Yeon Hee Park ◽  
So Youn Jung ◽  
Eun Sook Lee ◽  
...  

551 Background: Although young age breast cancer represents poor prognosis, no definitive explanation could have been made for the phenomenon. A tumor proliferation marker Ki67 is known to be a marker for both prognosis and prediction for chemotherapy responsiveness, and its level varies widely depending on the breast cancer subtype. This study was aimed to analyze Ki67 in relationship with age in hormone receptor positive breast cancer patients. Methods: We retrospectively reviewed 9061 consecutive cases of hormone receptor positive invasive breast cancer from data base at Seoul National University Hospital (SNUH) (between 2000 and 2012), Samsung Medical Center (SMC) (between 2004 and 2010), and National Cancer Center (NCC) (between 2001 and 2010) in Korea. Patients with estrogen receptor (ER) or progesterone receptor (PR) positive tumors were included irrespective of HER2 amplification. A multicenter data of Ki67 level identified by immunohistochemistry (IHC) and age at diagnosis were analyzed. Patients who underwent neoadjuvant systemic therapy were excluded. Results: Total 6222 cases from SNUH, 976 from SMC and 1863 from NCC were included. The three datasets were analyzed separately due to variable IHC methods in each institute. Mean ages were 49.30 years (range 20-86), 47.75 years (range 22-81) and 45.31 years (range 25-59), and mean Ki67 levels were 4.66% (range 1-100), 22.98% (range 1-97) and 14.58% (range 1-90), at SNUH, SMC, NCC respectively. Ki67 level was inversely proportional with age at diagnosis in all three datasets, and the level was significantly higher for patients <40 years compared to ≥40 years (mean Ki67: 5.97 vs 4.41, p<0.001; 28.60 vs 21.88, p<0.001; 17.01 vs 14.03, p<0.001, respectively). There was an inverse relation with age as well when Ki67 level was categorized into ‘<10% vs ≥10% (p<0.001)’, ‘<20% vs ≥20% (p=0.03)’ and ‘<14% vs ≥14% (p<0.001)’ respectively. Conclusions: Despite the variability of assessing Ki67 expression, Ki67 level was significantly higher in young age hormone receptor positive breast cancer from all three analyses. This could partly explain the poor prognosis and substantial responsiveness to chemotherapy in this age group of patients.


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