ABSTRACT
Molecular alterations in tumor-adjacent tissues have recently been recognized in some types of cancer. This phenomenon has not been studied in endometrial cancer. We aimed to analyze the expression of genes associated with cancer progression and metabolism in primary endometrial cancer samples and the matched tumor-adjacent tissues and in the samples of endometria from cancer-free patients with uterine leiomyomas. Paired samples of tumor-adjacent tissues and primary tumors from 49 patients with endometrial cancer (EC), samples of endometrium from 25 patients with leiomyomas of the uterus, and 4 endometrial cancer cell lines were examined by the RT-qPCR, for MYC, NR5A2, CXCR2, HMGA2, LIN28A, OCT4A, OCT4B, OCT4B1, TWIST1, STK11, SNAI1, and miR-205-5p expression. The expression levels of MYC, NR5A2, SNAI1, TWIST1, and STK11 were significantly higher in tumor-adjacent tissues than in the matched EC samples, and this difference was not influenced by the content of cancer cells in cancer-adjacent tissues. The expression of MYC, NR5A2, and SNAI1 was also higher in EC-adjacent tissues than in samples from cancer-free patients. In addition, the expression of MYC and CXCR2 in the tumor related to non-endometrioid adenocarcinoma and reduced the risk of recurrence, respectively, and higher NR5A2 expression in tumor-adjacent tissue increased the risk of death. In conclusion, tissues proximal to EC present higher levels of some cancer-promoting genes than the matched tumors. Malignant tumor-adjacent tissues carry a diagnostic potential and emerge as new promising target of anticancer therapy.
Subject(s)
Endometrial Neoplasms , Leiomyoma , MicroRNAs , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrium/metabolism , Female , Humans , Leiomyoma/pathology , MicroRNAs/geneticsABSTRACT
PURPOSE: The majority of non-small cell lung cancer (NSCLC) patients presents with an advanced-stage disease and, consequently, exhibits a poor overall survival rate. We aimed to assess changes in plasma miR-9, miR-16, miR-205 and miR-486 levels and their potential as biomarkers for the diagnosis and monitoring of NSCLC patients. METHODS: Plasma was collected from 50 healthy donors and from NSCLC patients before surgery (n = 61), 1 month after surgery (n = 37) and 1 year after surgery (n = 14). microRNA levels were quantified using qRT-PCR. RESULTS: We found in NSCLC patients before treatment, both with squamous cell carcinoma (SQCC) and adenocarcinoma (ADC), significantly higher plasma miR-16 and miR-486 levels than in healthy individuals. Pre-treatment miR-205 concentrations were found to be significantly higher in SQCC than in ADC patients, and only SQCC patients presented significantly higher circulating miR-205 levels than healthy donors. SQCC plasma miR-9 levels were not different from normal control levels, but in ADC they were found to be significantly decreased. A combination of plasma miR-16, miR-205 and miR-486 measurements was found to discriminate NSCLC patients from healthy persons, with a specificity of 95% and a sensitivity of 80%. Following tumor resection, we found that the miR-9 and miR-205 levels significantly decreased, even below the normal level, whereas the increased miR-486 level persisted up to one year after surgery, and the miR-16 level decreased to normal. After tumor resection, none of the miR levels tested was found to relate to recurrence. CONCLUSIONS: Our data indicate that miR-9, miR-16, miR-205 and miR-486 may serve as NSCLC biomarkers. The observed cancer-related pre- and post-operative changes in their plasma levels may not only reflect the presence of a primary cancer, but also of a systemic response to cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/surgery , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Male , MicroRNAs/blood , Middle Aged , Treatment OutcomeABSTRACT
Synovial sarcoma (SyS) occurs mostly in young adults and is characterized by an aggressive course. Combined treatment including chemotherapy, radiotherapy and surgical excision of the tumour is still not satisfactory, with mean 5-year survival of 30-50%. New targeted treatment options have appeared recently, e.g. HER2 and EGFR antagonists. Initial studies have revealed immunohistochemical overexpression of the EGFR in SyS; therefore trials with EGFR antagonist therapy have commenced. The aim of our study was to evaluate the status of HER2, EGFR and TOPIIA in SyS before and after combined therapy. Immunohistochemistry and FISH tests were performed. Significant discrepancies between protein expression and gene status were found. The authors discuss the potential reasons for that phenomenon.