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OBJECTIVE: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC). METHODS: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC). RESULTS: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%). CONCLUSIONS: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
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Antígeno Ca-125/sangue , Proteínas de Membrana/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Proteínas/metabolismo , Adulto , Algoritmos , Carcinoma Epitelial do Ovário , Diagnóstico Diferencial , Feminino , Humanos , Imunoensaio , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Fatores de Risco , Proteína 2 do Domínio Central WAP de Quatro DissulfetosRESUMO
DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B, and HER2-positive Breast Carcinoma (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). DSCAM-AS1 expression is analyzed in 30 public datasets and, additionally, by qRT-PCR in tumors from 93 BC patients, to uncover correlations with clinical data. Moreover, the effect of DSCAM-AS1 knockdown on gene expression and alternative splicing is studied by RNA-Seq in MCF-7 cells. We confirm DSCAM-AS1 overexpression in high grade Luminal A, B, and HER2+ BCs and find a significant correlation with disease relapse. In total, 908 genes are regulated by DSCAM-AS1-silencing, primarily involved in the cell cycle and inflammatory response. Noteworthily, the analysis of alternative splicing and isoform regulation reveals 2085 splicing events regulated by DSCAM-AS1, enriched in alternative polyadenylation sites, 3'UTR (untranslated region) shortening and exon skipping events. Finally, the DSCAM-AS1-interacting splicing factor heterogeneous nuclear ribonucleoprotein L (hnRNPL) is predicted as the most enriched RBP for exon skipping and 3'UTR events. The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.
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Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. Our goal was to examine the levels of ALCAM, in addition to the classical breast cancer tumor markers carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA), in serum by quantitative enzyme-linked immunosorbent assay for diagnosis in breast cancer patients. The 3 proteins were measured in serum of 100 healthy women, 50 healthy men and 150 breast carcinoma patients. The diagnostic sensitivity and specificity of the tests were calculated and the association of serum marker concentrations with various clinicopathologic variables was examined using nonparametric Kruskal-Wallis tests. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers. ALCAM, with area under the curve (AUC) of 0.78 [95% CI: 0.73, 0.84] outperformed CA15-3 (AUC = 0.70 [95% CI: 0.64, 0.76]) and CEA (AUC= 0.63 [95% CI: 0.56, 0.70]). The incremental values of AUC for ALCAM over that for CA15-3 were statistically significant (Delong test, p < 0.05). Combining CA15-3 and ALCAM yielded a ROC curve with an AUC of 0.81 (95% CI [0.75, 0.87]). Serum ALCAM appears to be a new biomarker for breast cancer and may have value for disease diagnosis.
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Antígenos CD/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Moléculas de Adesão Celular Neuronais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas Fetais , Humanos , Pessoa de Meia-Idade , Mucina-1/sangue , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Studies on factors affecting editorial decisions of scientific journals are scarce. In this study, we focused on case reports submitted to oncology journals and analyzed whether their nature or other relevant variables affected the chances of their acceptance. METHODS: We analyzed case reports submitted to 2 oncology journals: Tumori Journal and The International Journal of Biological Markers, and split them into 3 predefined groups: those (a) describing rare or unusual presentation of diseases, (b) describing the side effects of an intervention or (c) describing the success of a novel intervention. Publication status was retrospectively retrieved from the submission system, and acceptance rates were calculated taking into account other variables including geographic location of corresponding author. RESULTS: A total of 326 case reports were suitable for analysis. The acceptance rate was 35.4% for group (a), 27.9% for group (b), 19.6% for group (c) (p = 0.01). After correcting for other variables, the odds ratio (OR) of being accepted for group (c) was 0.58 (95% CI, 0.33-1.00) compared with the other groups combined. There was a highly significant difference of acceptance rates between manuscripts with authors coming from developed vs. developing countries that remained significant (OR = 5.94; 95% CI, 3.05-10.09) after correcting for multiple variables. CONCLUSIONS: The nature of a case report in oncology may affect acceptance rate, with case reports describing successful approaches or side effects of treatment being accepted with a higher frequency then case reports describing a rare clinical or diagnostic scenario. Also, works coming from developed countries are accepted significantly more frequently than case reports coming from developing countries.
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Oncologia , Editoração/normas , Humanos , Publicações Periódicas como Assunto/normasRESUMO
The Nanosized Cancer Polymarker Biochip Project (RBLA03S4SP) funded by an Italian MIUR-FIRB grant (Italian Ministry of University and Research - Investment Funds for Basic Research) has led to the creation of a free-access dynamic website, available at the web address https://serviziweb.ulss12.ve.it/firbabo, and of a centralized database with password-restricted access. The project network is composed of 9 research units (RUs) and has been active since 2005. The aim of the FIRB project was the design, production and validation of optoelectronic and chemoelectronic biosensors for the simultaneous detection of a novel class of cancer biomarkers associated with immunoglobulins of the M class (IgM) for early diagnosis of cancer. Biomarker immune complexes (BM-ICs) were assessed on samples of clinical cases and matched controls for breast, colorectal, liver, ovarian and prostate malignancies. This article describes in detail the architecture of the project website, the central database application, and the biobank developed for the FIRB Nanosized Cancer Polymarker Biochip Project. The article also illustrates many unique aspects that should be considered when developing a database within a multidisciplinary scenario. The main deliverables of the project were numerous, including the development of an online database which archived 1400 case report forms (700 cases and 700 matched controls) and more than 2700 experimental results relative to the BM-ICs assayed. The database also allowed for the traceability and retrieval of 21,000 aliquots archived in the centralized bank and stored as backup in the RUs, and for the development of a centralized biological bank in the coordinating unit with 6300 aliquots of serum. The constitution of the website and biobank database enabled optimal coordination of the RUs involved, highlighting the importance of sharing samples and scientific data in a multicenter setting for the achievement of the project goals.