Project description:PeCa is a rare carcinoma in developed countries, but it presents higher incidence rates in South America, Asia, and Africa, where limited economic and social conditions play a large impact leading to delay in diagnosis, and treatment initiation. The infection by HPV is a the risk factors and can occur through the canonical HPV/p53/RB1 pathway mediated by the E2/E6/E7 viral oncoproteins. During the transformation process, HPV inserts its genetic material into host Integration Sites (IS), affecting coding genes and miRNAs. In penile cancer (PeCa) there is limited data on the miRNAs. Considering the high frequency of HPV infection in PeCa patients in Northeast Brazil, global miRNA expression profiling was performed in high-risk HPV-associated PeCa. A panel of differentially expressed miRNAs (miRDE) was successfully constructed using 22 PeCa tissues and five non-tumor penile tissues.
Project description:Gene expression microarray was used to evaluate altered genes related and non related to HPV infection status in order to identify potential molecular markers in penile cancer (PC). RNA was extracted from thirty-nine fresh frozen PC samples and submitted to gene expression microarray. The normal penile pool consisted of total RNA from five autopsy glands. Specific gene expression alterations were investigated by RT-qPCR. DNA was also extracted from penile samples and submitted to HPV genotyping.
Project description:Array-based comparative genomic hybridization (aCGH) was used to evaluate DNA copy number alterations related and non related to HPV infection status aiming to identify potential molecular markers in penile cancer (PC).
Project description:Gene expression microarray was used to evaluate altered genes related and non related to HPV infection status in order to identify potential molecular markers in penile cancer (PC).
Project description:Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tumors. MiRNA expression profile was investigated by microrray analysis in the HPV-positive cervical cancer cell lines SiHa (HPV16-positive cell line derived from a cervical squamous cell carcinoma), CaSki (HPV16-positive cell line derived from a metastatic cervical epidermoid carcinoma), and HeLa (HPV18-positive cell line derived from a cervical adenocarcinoma) and compared with primary HFKs and C33a (HPV-negative cervical cell line).
Project description:Genome wide DNA methylation profiling of primary penile squamous cell carcinoma samples with lymphnode metastasis. The Illumina Infinium 450 K Human Methylation was used to obtain DNA methylation profiles in surgical frozen samples. Among the 25 samples, fifteen was infected with HPV, and the others were HPV negative.
Project description:Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested that miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profiles in human penile cancer have not been reported before. In this present study, the miRNA profiles were obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous penile tissues via NGS. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired penile tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various types of cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analysis suggested that the putative target genes of the differentially expressed miRNAs were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch, Hedgehog and TGF-β signaling pathways, which were all well-established to be involved in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifing the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.
Project description:Offering self-sampling for HPV testing improves the effectiveness of current cervical screening programs. Molecular triage markers directly applicable on self-samples are needed to further stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. MicroRNAs (miRNAs) deregulation has been implicated in the development of cervical cancer, and represents a potential class of triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self-samples. This study is the first to establish genome-wide miRNA profiles in HPV-positive self-samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self-samples. Small RNA sequencing (sRNA-Seq) was conducted to determine genome-wide miRNA expression profiles in 73 HPV-positive self-samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRidge, a penalized method on logistic regression. Classification of sRNA-Seq data yielded a panel of 9 miRNAs with a combined Area Under the Curve (AUC) of 0.89 for CIN3 detection. Six out of nine miRNAs were validated by qPCR in 165 independent HPV-positive self-samples and resulted in a combined AUC of 0.72 for CIN3+ detection. This study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected in HPV-positive self-samples using genome-wide miRNA profiling. Further validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self-samples.
Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.