INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice. INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.
- MeSH
- dospělí MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prsu * patologie genetika metabolismus mortalita MeSH
- regulace genové exprese u nádorů * MeSH
- RNA malá jaderná * genetika metabolismus MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease. OBJECTIVE: Evaluation of novel long non-coding RNAs biomarkers for breast cancer. METHODS: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics. RESULTS: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality. CONCLUSIONS: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.
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- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- dospělí MeSH
- guanylátkinasy genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prsu * genetika patologie metabolismus mortalita MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika MeSH
- senioři MeSH
- stupeň nádoru MeSH
- tumor supresorové geny MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. METHODS: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. RESULTS: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e. , AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. CONCLUSION: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis.
- MeSH
- dospělí MeSH
- endogenní retroviry * genetika MeSH
- karcinogeneze * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory prsu * virologie patologie genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Clinically silent uterine rupture with complete fetal expulsion into the abdominal cavity is an extremely rare complication. Diagnosis can be difficult and the risk to the mother and fetus is high. Conservative management has been described only in a few cases of partial expulsion of the fetus so far. CASE PRESENTATION: We present a case of 43-year-old tercigravida with a history of previous laparotomic myomectomy and subsequent cesarean section. The subsequent pregnancy was complicated by uterine wall loosening and rupture at the site of the previous uterine scar after myomectomy and complete fetal expulsion into the abdominal cavity. The diagnosis was made at 24 + 6 weeks of gestation. Considering the absence of clinical symptomatology and the good condition of the fetus, a conservative approach was chosen with intensive monitoring of the maternal and fetal conditions. The pregnancy ended by elective cesarean section and hysterectomy at 28 + 0 weeks of gestation. The postpartum course was uneventful and the newborn was discharged to home care 63 days after delivery. CONCLUSIONS: Fetal expulsion into the abdominal cavity after silent uterine rupture of the scarred uterus may be accompanied by minimal symptomatology making early diagnosis difficult. This rare complication must be considered in the differential diagnosis in women after major uterine surgery. In selected cases and under conditions of intensive maternal and fetal monitoring, conservative management may be chosen to reduce the risks associated with prematurity.
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- břišní dutina * MeSH
- císařský řez škodlivé účinky MeSH
- dospělí MeSH
- konzervativní terapie škodlivé účinky MeSH
- lidé MeSH
- novorozenec MeSH
- ruptura dělohy * etiologie chirurgie diagnóza MeSH
- těhotenství MeSH
- uterus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Ovarian cancer comprises the most lethal gynecologic malignancy and is accompanied by the high potential for the incidence of metastasis, recurrence and chemotherapy resistance, often associated with a formation of ascitic fluid. The differentially expressed ascites-derived microRNAs may be linked to ovarian carcinogenesis. The article focuses on a number of miRNAs that share a common expression pattern as determined by independent studies using ascites samples and with regard to their functions and outcomes in experimental and clinical investigations.Let-7b and miR-143 have featured as tumor suppressors in ovarian cancer, which is in line with data on other types of cancer. Although two miRNAs, i.e. miR-26a-5p and miR-145-5p, act principally as tumor suppressor miRNAs, they occasionally exhibit oncogenic roles. The performance of miR-95-3p, upregulated in ascites, is open to debate given the current lack of supportive data on ovarian cancer; however, data on other cancers indicates its probable oncogenic role. Different findings have been reported for miR-182-5p and miR-200c-3p; in addition to their presumed oncogenic roles, contrasting findings have indicated their ambivalent functions. Further research is required for the identification and evaluation of the potential of specific miRNAs in the diagnosis, prediction, treatment and outcomes of ovarian cancer patients.
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- ascites genetika MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádory vaječníků * patologie MeSH
- regulace genové exprese u nádorů MeSH
- stanovení celkové genové exprese MeSH
- tumor supresorové geny MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas). METHODS AND RESULTS: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival. CONCLUSIONS: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer.
- MeSH
- biologické markery MeSH
- lidé MeSH
- mikro RNA * metabolismus MeSH
- nádorové biomarkery genetika MeSH
- nádory prsu * diagnóza genetika patologie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- regulace genové exprese u nádorů genetika MeSH
- RNA malá jaderná MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: To determine the benefit of contrast-enhanced ultrasound (CEUS) in the assessment of breast lesions. METHODS: A standardized contrast-enhanced ultrasound was performed in 230 breast lesions classified as BI-RADS category 3 to 5. All lesions were subjected to qualitative and quantitative analysis. MVI (MicroVascular Imaging) technique was used to derive qualitative analysis parameters; blood perfusion of the lesions was assessed (perfusion homogeneity, type of vascularization, enhancement degree). Quantitative analysis was conducted to estimate perfusion changes in the lesions within drawn regions of interest (ROI); parameters TTP (time to peak), PI (peak intensity), WIS (wash in slope), AUC (area under curve) were obtained from time intensity (TI) curves. Acquired data were statistically analyzed to assess the ability of each parameter to differentiate between malignant and benign lesions. The combination of parameters was also evaluated for the possibility of increasing the overall diagnostic accuracy. Biological nature of the lesions was verified by a pathologist. Benign lesions without histopathological verification (BI-RADS 3) were followed up for at least 24 months. RESULTS: Out of 230 lesions, 146 (64%) were benign, 67 (29%) were malignant, 17 (7%) lesions were eliminated. Malignant tumors showed statistically significantly lower TTP parameters (sensitivity 77.6%, specificity 52.7%) and higher WIS values (sensitivity 74.6%, specificity 66.4%) than benign tumors. Enhancement degree also proved to be statistically well discriminating as 55.2% of malignant lesions had a rich vascularity (sensitivity 89.6% and specificity 48.6%). The combination of quantitative analysis parameters (TTP, WIS) with enhancement degree did not result in higher accuracy in distinguishing between malignant and benign breast lesions. CONCLUSIONS: We have demonstrated that contrast-enhanced breast ultrasound has the potential to distinguish between malignant and benign lesions. In particular, this method could help to differentiate lesions BI-RADS category 3 and 4 and thus reduce the number of core-cut biopsies performed in benign lesions. Qualitative analysis, despite its subjective element, appeared to be more beneficial. A combination of quantitative and qualitative analysis did not increase the predictive capability of CEUS.
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- diferenciální diagnóza MeSH
- dospělí MeSH
- kontrastní látky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory prsu diagnostické zobrazování patologie MeSH
- prospektivní studie MeSH
- prsy diagnostické zobrazování patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- stupeň nádoru MeSH
- ultrasonografie prsů metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
High grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is the deadliest gynecological disease which results in a five-year survival rate of 30% or less. HGSC is characterized by the early and rapid development of metastases accompanied by a high frequency of ascites i.e. the pathological accumulation of fluid in peritoneum. Ascites constitute a complex tumor microenvironment and contribute to disease progression by largely unknown mechanisms. Methods: Malignant ascites obtained from HGSC patients who had undergone cytoreductive surgery were tested for their ability to induce WNT signaling in the Kuramochi cell line, a novel and clinically relevant in vitro model of HGSC. Next, cancer spheroids (the main form of metastatic cancer cells in ascites) were evaluated with respect to WNT signaling. Kuramochi cells were used to determine the role of individual WNT signaling branches in the adoption of metastatic stem cell-like behavior by HGSC cells. Furthermore, we analyzed genomic and transcriptomic data on WNT/Planar Cell Polarity (PCP) components retrieved from public cancer databases and corroborated with primary patient samples and validated antibodies on the protein level. Results: We have shown that ascites are capable of inducing WNT signaling in primary HGSC cells and HGSC cell line, Kuramochi. Importantly, patients whose ascites cannot activate WNT pathway present with less aggressive disease and a considerably better outcome including overall survival (OS). Functionally, the activation of non-canonical WNT/PCP signaling by WNT5A (and not canonical WNT/β-catenin signaling by WNT3A) promoted the metastatic stem-cell (metSC) like behavior (i.e. self-renewal, migration, and invasion) of HGSC cells. The pharmacological inhibition of casein kinase 1 (CK1) as well as genetic ablation (dishevelled 3 knock out) of the pathway blocked the WNT5A-induced effect. Additionally, WNT/PCP pathway components were differentially expressed between healthy and tumor tissue as well as between the primary tumor and metastases. Additionally, ascites which activated WNT/PCP signaling contained the typical WNT/PCP ligand WNT5A and interestingly, patients with high levels of WNT5A protein in their ascites exhibited poor progression-free survival (PFS) and OS in comparison to patients with low or undetectable ascitic WNT5A. Together, our results suggest the existence of a positive feedback loop between tumor cells producing WNT ligands and ascites that distribute WNT activity to cancer cells in the peritoneum, in order to promote their pro-metastatic features and drive HGSC progression. Conclusions: Our results highlight the role of WNT/PCP signaling in ovarian cancerogenesis, indicate a possible therapeutic potential of CK1 inhibitors for HGSC, and strongly suggest that the detection of WNT pathway inducing activity ascites (or WNT5A levels in ascites as a surrogate marker) could be a novel prognostic tool for HGSC patients.
- MeSH
- ascites metabolismus patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí fyziologie MeSH
- nádory vaječníků metabolismus mortalita patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- signální dráha Wnt * MeSH
- stupeň nádoru MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
