Expression of uc.189 and its clinicopathologic significance in gynecological cancers.
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ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC5800915 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Most cancers are old age-related diseases. Patients with lymphatic metastasis have an extremely poor prognosis in esophageal cancers (ECs). Previous studies showed ultraconserved RNAs are involved in tumorigenesis and ultraconserved RNA 189 (uc.189) served as an oncogene in cervical cancer, but the effect of exosomal uc.189 in esophageal squamous cell carcinoma (ESCC) remains undefined. This study revealed that uc.189 is closely correlated with lymph node (LN) metastasis and the number of lymphatic vessels in ESCC. ESCC-secreted exosomal uc.189 is transferred into human lymphatic endothelial cells (HLECs) to promote its proliferation, migration and tube formation to facilitate lymph node metastasis. Mechanistically, uc.189 regulated EPHA2 expression by directly binding to its 3'UTR region through dual-luciferase reporter assay. Over-expression and knockdown of EPHA2 could respectively rescue and simulate the effects induced by exosomal uc.189. Especially, the uc.189-EPHA2 axis activates the P38MAPK/VEGF-C pathway in HLECs. Finally, ESCC-secreted exosomal of uc.189 promotes HLECs sprouting in vitro, migration, and lymphangiogenesis. Thus, these findings suggested that exosomal uc.189 targets the EPHA2 of HLECs to promote lymphangiogenesis, and may represent a novel marker of diagnosis and treatment for ESCC patients in early stages.
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Project description:OBJECTIVE:Cytokeratin 5/6 and Cytokeratin 8/18 are basal and luminal markers of breast cancer and they have pathological and prognostic significance in breast cancer. We performed Cytokeratin 5/6 and CK8/18 immunohistochemistry on 150 cases of triple negative breast cancers and association with various clinicopathological features was evaluated. RESULTS:Positive CK5/6 expression was noted in 8% (12 cases) of TNBC while 2.4% (4 cases) showed focal positive (<?10%) and 89.3% (134) were negative with CK5/6. Complete loss of CK8/18 expression was seen in 4.7% (7 cases) while 32.7% (49 cases) revealed focal loss of CK8/18 and 62.7% (94 cases) showed intact normal expression of CK8/18. No significant association of CK5/6 and CK8/18 with various clinicopathological parameters was observed. We found a low expression of basal cytokeratin (CK5/6) in TNBC our studied population, while loss/altered expression of CK8/18 in approximately 38% of TNBC. Although no prognostic relevance of these finding was noted in our study, however these findings are different from those reported in literature in other parts of the world. Therefore we suggest a more through immunohistochemical and genomic profiling of TNBC in our population for better understanding of this disease in this part of the world.
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Project description:PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications.
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Project description:The clinical value of SIRT1 in hepatocellular carcinoma (HCC) remains controversial. This meta-analysis was performed to investigate the prognostic and clinicopathological significance of the histone deacetylase SIRT1 in HCC. Pooled hazard ratios (HRs) for survival outcomes and pooled odds ratios (ORs) for clinical parameters associated with SIRT1 were calculated in nine studies using Review Manager. Meta-analysis showed that increased SIRT1 expression is associated with poor overall survival (OS) (HR=1.82, 95% confidence interval (CI): 1.49-2.22, P<0.00001) and disease-free survival (DFS) (HR=1.44, 95%CI: 1.06-1.96, P=0.02) in HCC. Increased expression of SIRT1 is more common in female than male HCC patients (OR=0.47, 95%CI: 0.32-0.70, P=0.0001). The increased SIRT1 expression correlates with hepatitis B virus (HBV) infection (OR=1.63, 95%CI: 1.04-2.57, P=0.03), large tumor size (OR=1.81, 95%CI: 1.05-3.13, P=0.03), high p53 expression (OR=2.71, 95%CI: 1.39-5.29, P=0.003), high levels of alpha-fetoprotein (AFP; cutoff value: 400 ng/ml, OR=1.84, 95%CI: 1.26-2.69, P=0.002), and tumor stage (OR=1.72, 95%CI: 1.27-2.32, P=0.0004). Re-sampling statistics for 5,000,000 samples revealed that increased SIRT1 expression is associated with higher TNM stage (OR=1.70, 95%CI: 1.69-1.70, P<0.00001). These results indicate that SIRT1 is a new biomarker off HCC as well as a potentially effective therapeutic target.
| S-EPMC5581034 | biostudies-literature
Project description:HLA-E is a nonclassical HLA class I molecule, which differs from classical HLA molecules by its nonpolymorphic, conserved nature. Expression and function of HLA-E in normal tissues and solid tumors is not fully understood. We investigated HLA-E protein expression on tissue sections of 420 ovarian and cervical cancers and found equal or higher levels than normal counterpart epithelia in 80% of the tumors. Expression was strongly associated with components of the antigen presentation pathway, e.g., transporter associated with antigen processing (TAP), endoplasmic reticulum aminopeptide (ERAP), ?2 microglobulin (?2m), HLA classes I and II, and for ovarian cancer with tumor infiltrating CD8(+) T lymphocytes (CTLs). This association argues against the idea that HLA-E would compensate for the loss of classical HLA in tumors. In situ detection of HLA-E interacting receptors revealed a very low infiltrate of natural killer (NK) cells, but up to 50% of intraepithelial CTLs expressed the inhibiting CD94/NKG2A receptor. In cervical cancer, HLA-E expression did not alter the prognostic effect of CTLs, most likely due to very high infiltrating CTL numbers in this virus-induced tumor. Overall survival of ovarian cancer patients, however, was strongly influenced by HLA-E, because the beneficial effect of high CTL infiltration was completely neutralized in the subpopulation with strong HLA-E expression. Interestingly, these results indicate that CTL infiltration in ovarian cancer is associated with better survival only when HLA-E expression is low and that intratumoral CTLs are inhibited by CD94/NKG2A receptors on CTLs in the tumor microenvironment.
| S-EPMC3127933 | biostudies-literature
Project description:BackgroundAnoctamin-1 (ANO1) plays a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of ANO1 in cancers.MethodsA total of 1760 patients from 7 eligible studies were included into the analysis. Pooled hazard ratios or odds ratios were extracted and calculated with a random-effects model, and analyses of heterogeneity bias were conducted.ResultsOur results showed that over expression of ANO1 was significantly correlated with poor overall survival in all cancers (HR = 1.52; 95% CI: 1.19-1.92; P = .0006). Subgroup analysis indicated that there was a significant association between over expression of ANO1 and poor prognosis breast cancer (HR = 3.24; 95% CI: 1.74-6.04), head and neck squamous cell carcinoma (HR = 1.14; 95% CI: 1.00-1.30), esophageal squamous cell carcinoma (HR = 1.93; 95% CI: 1.07-3.50), gastric cancer (HR = 1.62; 95% CI: 1.12-2.34) and colorectal cancer (HR = 1.38; 95% CI: 1.03-1.85). In addition, over expression of ANO1 was not associated with TNM stage, histological grade, lymph node metastasis, tumor size, age and gender. However, ANO1 was significantly associated with human epidermal growth factor receptor 2, but not associated with progesterone receptor or estrogen receptor in breast cancer.ConclusionsOur results indicate that ANO1 can be a predictive factor for prognosis of cancer.
| S-EPMC7850693 | biostudies-literature
Project description:PURPOSE:Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer. However, concerning the adverse effects of NSAIDs and COXibs, it is still urgent and necessary to explore novel and specific anti-inflammation targets for potential chemoprevention. The signaling of cyclooxygenase 2-prostaglandin E2-prostaglandin E2 receptors (COX-2-PGE2-EPs) is the central inflammatory pathway involved in the gynecological carcinogenesis. METHODS:Literature searches were performed to the function of COX-2-PGE2-EPs in gynecological malignancies. RESULTS:This review provides an overview of the current knowledge of COX-2-PGE2-EPs signaling in endometrial cancer, ovarian cancer and cervical cancer. Many studies demonstrated the upregulated expression of the whole signaling pathway in gynecological malignancies and some focused on the function of COX-2 and cAMP-linked EP2/EP4 and EP3 signaling pathway in gynecological cancer. By contrast, roles of EP1 and the exact pathological mechanisms have not been completely clarified. The studies concerning EP receptors in gynecological cancers highlight the potential advantage of combining COX enzyme inhibitors with EP receptor antagonists as therapeutic agents in gynecological cancers. CONCLUSION:EPs represent promising anti-inflammation biomarkers for gynecological cancer and may be novel treatment targets in the near future.
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Project description:Grief and hope are two conflicting emotions that a patient recently diagnosed with cancer has to master. The real challenge for gynecologic oncologists is how to reach out. Conventional wisdom states that offering patients focus and belief when combating cancer in their lives allows them to embrace hope with greater confidence, which minimizes their grief. Three pictorial models are presented: '4-cusp approach' model used at the initial consultation; 'tapestry of bereavement or landscape of grief' model at the postsurgery consultation; and 'Venn-diagram' model at any time during patient management. We have applied these models in our practice and believe that they can act as a fulcrum for the patient, the family and healthcare team around which therapy should be centered.
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Project description:Angiogenesis, or generation of new blood vessels from other pre-existing, is a key process to maintain the supply of nutrients and oxygen in tissues. Unfortunately, this process is exacerbated in pathologies such as retinopathies and cancers with high angiogenesis as ovarian cancer. Angiogenesis is regulated by multiple systems including growth factors and neurotrophins. One of the most studied angiogenic growth factors is the vascular endothelial growth factor (VEGF), which is overexpressed in several cancers. It has been recently described that neurotrophins could regulate angiogenesis through direct and indirect mechanisms. Neurotrophins are a family of proteins that include nerve growth factor (NGF), brain-derived growth factor (BDNF), and neurotrophins 3 and 4/5 (NT 3, NT 4/5). These molecules and their high affinity receptors (TRKs) regulate the development, maintenance, and plasticity of the nervous system. Furthermore, it was recently described that they display essential functions in non-neuronal tissues, such as reproductive organs among others. Studies have shown that several types of cancer overexpress neurotrophins such as NGF and BDNF, which might contribute to tumor progression and angiogenesis. Besides, in recent years the FDA has approved the use of pharmacologic inhibitors of pan-TRK receptors in patients with TRKs fusion-positive cancers. In this review, we discuss the mechanisms by which neurotrophins stimulate tumor progression and angiogenesis, with emphasis on gynecological cancers.
| S-EPMC6761325 | biostudies-literature
Project description:BackgroundGastric cancer (GC) patients frequently develop peritoneal metastasis. Recently, it has been reported that peritoneal mesothelial cells (PMCs) activated by GC cells acquire a migratory capacity and promote GC cell invasion. The invasiveness of PMCs reportedly depends on the activity of Tks5, an adaptor protein required for invadopodia formation. However, the relationship between clinicopathologic features and Tks5 expression in PMCs has been poorly documented. In this study, we evaluated the clinicopathologic significance of the Tks5 expression of PMCs in GC patients.Materials and methodsA total of 110 GC patients who underwent gastrectomy were enrolled in this study. Tks5 expressions in PMCs from the greater omentum, lesser omentum and retroperitoneum were evaluated by immunohistochemistry. We analyzed the correlation between Tks5 expressions in PMCs and the patients' clinicopathologic features.ResultsTks5 expression was found in 71 (64.5%) of the 110 patients, while 39 (35.5%) were Tks5-negative. Tks5 positivity was significantly (p = 0.038) associated with a greater tumor depth (i.e., T3/4 compared with T1/T2). Peritoneal recurrence was found in 12 of 98 cases within 3 years of surgery. The 3-year peritoneal recurrence-free survival (PRFS) rate in Tks5-positive cases was significantly poorer than that in Tks5-negative cases (80.1% vs 97.4%, p = 0.024). Multivariate analysis revealed that Tks5 positivity and lymph node metastasis were independent factors for PRFS.ConclusionTks5 is frequently expressed in PMCs in advanced-stage gastric cancer. Tks5 might be a useful predictor for peritoneal recurrence in GC patients.
| S-EPMC8277061 | biostudies-literature