ABSTRACT
In NSCLC, the altered expression of some miRNAs in primary tumor tissues has been correlated with diagnosis and prognosis, while the role of circulating miRNAs as cancer biomarkers is currently emerging. MiRNA expression profile through miRNA Affymetrix array was evaluated on a training set formed by the tumor component (n = 30 NSCLC serum, n = 11/30 tumor tissues) and the control component (n = 10 healthy serum and n = 11/30 noncancerous counterparts). Statistical analyses highlighted the following: a = 55 miRNAs deregulated in tumor serum, b = 27 miRNAs deregulated in tumor tissues, and c = 2 miRNAs deregulated both in tumor serum and in tumor tissues. MiRwalk tool and enrichment pathway analyses selected some miRNAs whose target genes are correlated with the main pathways involved in NSCLC tumorigenesis. The altered expression of the selected miR-486-5p (a), miR-29c* (b), and miR-133a (c) was confirmed in the validation set (n = 40). MiR-486-5p had a higher expression in tumor serum than in tumor tissues (P = 0.004), and miR-29c* showed a lower expression in tumor tissues than in tumor serum (P < 0.001). MiR-133a had a not different expression in both tumor serum and tumor tissues (P = 0.07). The low level of miR-486-5p expression in the serum of affected patients was associated with a worse time to progression of disease (P = 0.010), and serum level of miR-486-5p was a significant prognostic indicator of NSCLC (adjusted hazard ratio = 0.179, P = 0.019). These data suggest the possibility to monitor affected patients through serum and/or tissue samples, analyzing the altered expression of specific miRNAs, in order to detect prognostic biomarkers in the NSCLC.
Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma, Non-Small-Cell Lung/genetics , MicroRNAs/biosynthesis , Prognosis , Aged , Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , MicroRNAs/genetics , Microarray Analysis , Middle AgedABSTRACT
The molecular scenario of breast cancer has become more complex in the last few years. Distinguishing between BRCA-associated, sporadic, HER2-enriched and triple-negative tumors is not sufficient to allow effective clinical management. Basal-like breast cancer, a subtype of triple-negative breast cancer, differs from others grouped under this heading. Commonalities between BRCA-related tumors and basal-like breast cancers (BRCAness phenotype) are highly relevant to ongoing clinical trials, in particular those investigating targeted therapies (e.g. PARP inhibitors) in sporadic breast tumors. The 'gold standard' to identify basal-like phenotype is DNA microarray, but integrated results could provide a panel of biomarkers helpful in identifying 'BRCAness' tumors (e.g. copy number aberrations, abnormal protein localization and altered transcriptional levels) and other molecular targets, such as APE1,the inhibition of which is emerging as an attractive breast cancer treatment in certain therapeutic settings.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Receptor, ErbB-2/genetics , Triple Negative Breast Neoplasms/genetics , BRCA1 Protein/metabolism , BRCA2 Protein/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Female , Humans , Molecular Targeted Therapy , Poly(ADP-ribose) Polymerase Inhibitors , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/therapyABSTRACT
Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients.