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  • 1
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    Sa1900 Association of miR-146a, -miR-155, and miR-215 and Their mRNA Targets With Gastric Precancerous Lesions
    Elsevier BV ; 2015
    In:  Gastroenterology Vol. 148, No. 4 ( 2015-04), p. S-350-
    Details
    In: Gastroenterology, Elsevier BV, Vol. 148, No. 4 ( 2015-04), p. S-350-
    Type of Medium: Online Resource
    ISSN: 0016-5085
    URL: Article
    DOI: 10.1016/S0016-5085(15)31174-4
    RVK:
    XA 44500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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  • 2
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    Comparative analysis of miRNA profile in human dendritic cells infected with respiratory syncytial virus and human metapneumovirus
    Springer Science and Business Media LLC ; 2018
    In:  BMC Research Notes Vol. 11, No. 1 ( 2018-12)
    Details
    In: BMC Research Notes, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1756-0500
    URL: Article
    DOI: 10.1186/s13104-018-3541-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
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  • 3
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    Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-03-22)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-03-22)
    Abstract: This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-85930-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
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    Abstract 267: microRNA expression analysis in hrHPV positive FFPE tissues for the detection of cervical disease
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 267-267
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 267-267
    Abstract: Cervical cancer ranks first in cancer mortality among women of low-middle income countries where 80% of the 570,000 cases and 311,000 worldwide deaths estimated for 2018 occurred. Persistent infections with high-risk HPV (hrHPV) genotypes can lead to cervical high-grade lesions (Cervical Intraepithelial Neoplasia grade 2 or more severe disease, CIN-II+), that if left untreated progress to cancer. hrHPV test has high sensitivity but because many women infected with hrHPV genotypes will clear the infection spontaneously, it has low specificity to detect CIN-II+. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and show differential profiles in cervical intraepithelial lesions. Our aim was to identify miRNAs differentially expressed in CIN-II+ and to evaluate their potential use as biomarkers to distinguish low from high-grade lesions in hrHPV positive women. Methods We compared the miRNAs expression pattern between Formalin-Fixed Paraffin-Embedded (FFPE) tissues from hrHPV positive women with low-grade lesions (n=10) and women with high-grade lesions (n=10) of Medellin, Colombia, using the QIAseq miRNA Library Kit (Qiagen) and sequencing reagents and protocols from Illumina. The miRNAs with low coefficient of variation and high fold change were further validated by RT-PCR (miR-133a-3p, 143-3p, 143-5p, 29a-3p and 30b-5p) using miRCURY LNA miRNA PCR kit (Qiagen) and SNORD44 as housekeeping gene. Receiver Operating Characteristic (ROC) analyses with 95% confidence interval of the area under the curve were used to evaluate the diagnostic accuracy of the 5 miRNA and their combinations and the maxim Youden index to determine the optimal specificity and sensitivity. Results The differential miRNAs expression analysis identified 25 miRNAs overexpressed in high- versus low-grade lesions. The relative expression by RT-PCR of 5 of those miRNAs was higher in high-grade when compared to low-grade, and the levels of miR-143-3p, 143-5p and 30b-5p increased with disease progression (from healthy, CIN-I, CIN-II, CIN-III+). ROC analyses showed that miR-143-5p and the combination with miR-133a-3p exhibits the highest AUC 79% (95% CI: 65-93). However, the highest sensitivity is given by miR-29a-3p, 87.50% (95% CI: 67.64 - 97.34), and the highest specificity is given by miR-30b-5p, 95.45% (95% CI: 77.16-99-88), with cut-offs of & gt;1,157 and & gt;3,345 respectively. In conclusion, we identified 25 candidate miRNAs biomarkers and validated 5 of them with good diagnostic performance to distinguish high-grade from low-grade cervical lesions. Further validation on a larger cohort of samples is needed to confirm the potential role of these microRNAs to triage HPV positive women. Citation Format: Martha I. Gonzalez, Jone Garai, Jovanny Zabaleta, Gloria I. Sanchez. microRNA expression analysis in hrHPV positive FFPE tissues for the detection of cervical disease [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 267.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-267
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 5
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    Abstract P6-01-40: Integrative transcriptomic analysis and cohort validation identify key genes in chemotherapy treatment response in Latino breast cancer patients
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P6-01-40-P6-01-40
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P6-01-40-P6-01-40
    Abstract: Purpose: Breast cancer (BC) is one of the most frequent invasive cancers and one of the main causes of cancer mortality in women. Effective treatment interventions for BC are urgently required to improve survival rate and quality of life. Chemotherapy has been widely applied in BC treatment; however, therapeutic resistance remains an unresolved issue. Currently, only a minority of patients benefit from chemotherapy, emphasizing the need to identify more effective hub genes associated with therapy response. The overarching goal of this study is to assess hub genes correlated with BC chemotherapy treatment response via multiple databases and validate the workflow in an independent cohort of Hispanic/Latino (Colombian) women diagnosed with invasive Luminal B BC candidates for neoadjuvant chemotherapy. Design: Screening and multistep filtering of common genes correlated with chemotherapeutic response was performed by integrating differentially expressed genes between responders and non-responders in publicly available datasets. For each database, the differentially expressed genes (DEGs) between non-responders and responders were identified using GEO2R and LIMMA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the identified common genes using Metascape and DAVID. Functional enrichment analysis and protein-protein interaction (PPI) network for DEGs were constructed using (STRING) database. Hub genes were identified from PPI network by Cytoscape software analysis. The mRNA expression of hub genes in BC and normal tissues was subsequently explored by UALCAN. Evaluation of the effect of hub genes on survival was performed using Kaplan-Meier plotter. Hub genes were imported into the DGIdb to obtain the potential for BC chemotherapy-associated treatment drugs. The previous workflow was then applied/validated to an Illumina high-throughput RNA sequencing of 50 Luminal B cases (HER2+ and HER2-) of Hispanic/Latino patients. Results: 490 DEGs were obtained from the intersection of five public databases. Pathway enrichment analysis revealed DEGs were associated with cell cycle, estrogen response, adaptive immune response, and regulation of kinase activity, among others. Thirty-two hub genes were identified from PPI network analysis with high degree nodes and betweennesscentrality. Significant differential expression of hub genes between BC tissue and normal tissues was observed in UALCAN. These genes were significantly associated with survival probability. Fifteen potential targeted therapeutic drugs were identified through DGIdb database. Validation workflow in independent Luminal B cohort showed 238 DEGs, 90 hub genes with high degree and enrichment in the regulation of hormone levels, cellular response to EGFR, signaling by ERBB2 and MAPK. GATA3 was the hub gene found in both databases and the validation set. Both databases and validation set show hub genes, enriched pathways, and drugs that indicate their close association with tumorigenesis and would contribute to acting an important role in therapy response prediction. Conclusions: This workflow was created using public databases and applied to a patient’s cohort of different ancestries. This methodology can successfully provide potential biomarkers that correlate with therapy response. Genes were selected from PPI network. Most of them were independent biomarkers of BC treatment response, including that in underrepresented patients. Moreover, these genes may exert critical function in non-response and progression. Citation Format: Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Juan C. Mejia-Henao, Patricia López-Correa, Sandra Diaz, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita. Integrative transcriptomic analysis and cohort validation identify key genes in chemotherapy treatment response in Latino breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-40.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P6-01-40
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 6
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    Abstract PR05: Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 26, No. 2_Supplement ( 2017-02-01), p. PR05-PR05
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 26, No. 2_Supplement ( 2017-02-01), p. PR05-PR05
    Abstract: Background: Differences in outcome of breast cancer according to race/ethnicity have been reported. African American women have higher breast cancer-specific mortality rates compared to non-Hispanic White women (NHW). Although these differences have been attributed to the high prevalence of basal-like subtype among African Americans, these women have also less favorable outcome in less aggressive tumors when compared to NHW. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable levels of European, Native American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Latinas compared to NHW even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but knowledge is lacking in Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B. In this study we explored ancestry-associated differences in molecular profiles of luminal B tumors among these highly admixed women. Methods: To identify ancestry-associated differentially expressed genes in Luminal B tumors, we performed a whole-transcriptome RNA-seq analysis in 42 luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to luminal subtype and to the proportion of European ancestry (Low European ancestry group: ancestry proportion below the median; High European ancestry: ancestry proportion above the median).. We compared luminal B against luminal A tumors according to the assigned ancestry groups. We used DESeq2 package form R to test differential gene expression between the two tumor subtypes and by ancestry category. Genes with adjusted pvalue less than 0.05 were considered statistical significant. Results: We found 30 differentially expressed genes (pvalue & lt; 0.05) by genetic ancestry among Luminal B tumors from which 27 were differentially expressed in the less European luminal B tumors and 3 in the more European group. Tests of interaction suggest that ancestry is a statistically significant modifier of expression for the following genes for Low European Ancestry group: CENPF, SNORA54, AIF1L, TNFSF13, LRRC1, ARHGAP33, ONECUT2, CDK12, BUB1, NTRK2, HES1); and FDXACB1, RAB26, ATP8B3 for the High European Ancestry group. An exploratory analysis of these genes reveals enrichment of pathways associated to ERBB signaling in the Low European Ancestry group. Conclusions: Our results suggest that the proportion of European genetic ancestry in Colombian women might modify gene expression in luminal B tumors. Further analysis will be needed to confirm these findings. Citation Format: Silvia J. Serrano-Gomez, Carolina Sanabria, Melody C. Baddoo, Nataly Cruz-Rodriguez, Jone Garai, Gustavo Hernandez-Suarez, Juan Carlos Mejia, Lucio Miele, Chindo Hicks, Laura Fejerman, Jovanny Zabaleta. Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR05.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1538-7755.DISP16-PR05
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 7
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    Abstract IA06: Understanding the molecular landscape of gastric premalignant lesions
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 6_Supplement_1 ( 2020-06-01), p. IA06-IA06
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 6_Supplement_1 ( 2020-06-01), p. IA06-IA06
    Abstract: Even though the incidence of gastric cancer has been declining over the years, it still has a very high mortality rate. The incidence and mortality of gastric cancer is, however, significantly higher in minority populations with African Americans and Hispanic individuals presenting 52% and 43%, respectively, more cases than Caucasians (data for male patients). Gastric adenocarcinoma has been strongly associated to infection with Helicobacter pylori (H. pylori). The infection triggers an inflammatory cascade, known as the Correa's cascade, that changes the normal gastric epithelium into nonatrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. It is known that these events involve immune infiltration and damage to the gastric mucosa; however, there is still too much to learn about the gastric premalignant stages and the evolution of them over time. Over the years we have identified single-nucleotide polymorphisms (SNPs) and differential expression of genes associated with premalignant stages and with evolution of the disease over time. We found that African Americans have increased incidence of advanced premalignant lesions and have more prevalence of infection with H. pylori than Whites. In addition, we found that SNPs and haplotypes in the interleukin 1 b gene (IL1B) are associated with advanced gastritis in African American individuals. Interestingly, the frequency of these inflammatory SNPs and haplotypes is different among African American and Caucasian individuals. In terms of gene expression, we have also found that the increased expression of the gene deleted in malignant brain tumors 1 (DMBT1) is associated with the development of advanced gastritis while the expression of CD44 is associated with progression of the disease over time. Given that CD44 is a molecule involved in the homing of inflammatory cells, its association with progression of premalignant stages over time highlights the role of the immune response in the outcome of these lesions. Interestingly, these immune responses seem to be also modulated by H. pylori itself. We have shown that H. pylori components are able to modulate acquired and innate immune responses. In addition, we have also found a microRNA pattern associated with advanced premalignant gastric lesions in both African Americans and Caucasians. Understanding the molecular landscape of the gastric lesions may help us devise strategies to intervene and limit their progression into more advanced lesions, including gastric cancer. Citation Format: Jone Garai, Maria B. Piazuelo, Maria C. Camargo, Pelayo Correa, Keith Wilson, Jovanny Zabaleta. Understanding the molecular landscape of gastric premalignant lesions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA06.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1538-7755.DISP18-IA06
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 8
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    Abstract 3618: Mutational analysis of colon tumors from African American patients and potential association with cancer disparities
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3618-3618
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 3618-3618
    Abstract: Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. We have previously demonstrated that colon tumors from AA and CA differ in their immune cell recruitment and their systemic cytokines secretion profiles. Therefore, in this study we investigated if differences in gene expression and mutational profiles could relate to the disparities observed between these populations. Methods: We examined gene expression of colon tumor and non-tumor adjacent tissues from AA (n=20) and CA (n=20) by whole transcriptome sequencing (Illumina); and determined the differential expression of the 170 genes of the Illumina's TruSight Tumor 170 panel (TST170) in AA (n=12) and CA (n=17) colon tumor and non-tumor adjacent tissues. Results: From our gene expression studies, we found that colon tumors from AA patients showed significant fold-change increases in gene expression when compared to CA for FOXP3 (6.97 vs. 3.15), IL1B (122 vs. 14) and IL8 (262 vs. 28) (p & lt; 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and immunotherapy targets PDL1 (CD274) and CTLA4 (p & lt; 0.05). Through our mutational profiling we identified 38 genes in AA and 6 in CA differentially expressed between tumor and non-tumor tissues (p & lt; 0.01). Of those, 5 genes associated with several roles in cancer ETV4 (poor prognosis), CCND1 (tumorigenesis), FGFR2 (activation of the RAS-MAPK and the PI3K-AKT pathways) BRCA2 (genome stability), BCL2 (apoptosis regulator) were commonly altered in both cohorts. Conclusions: Our study demonstrates significant differences in the genetic characteristics of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense features in terms of gene expression. We also observed divergence in the mutational profiling between the groups, including numerous genes that are indicative of prognosis, treatment and outcomes in colon cancer. As such, these deficits could be mitigated through population-specific therapeutic approaches. Citation Format: Jenny Paredes, Jone Garai, Li Li, Melody Baddoo, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Mubarak Akadri, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Jennie L. Williams, Laura Martello-Rooney, Jovanny Zabaleta. Mutational analysis of colon tumors from African American patients and potential association with cancer disparities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3618.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-3618
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 9
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    Abstract 2729: Cell infiltration prediction of breast cancer tissues identifies basophils as potentially important immune cells in the tumor microenvironment
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2729-2729
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2729-2729
    Abstract: Background: Breast cancer (BC) is the most common and deadliest cancer in women worldwide. Hormone receptor (HR) positive tumors (luminal) are the most frequent while HER-2 overexpressing (HR-, HER2+) and triple negative (TNBC, HR-/HER2-) are most deadly. HR+ subtypes are more common in non-Hispanic White women while HER-2 and TNBC present either higher prevalence or risk of mortality in minority groups. Hispanic/Latinos (H/L) is the largest and fastest growing minority in the U.S.A. However, H/L women have been underrepresented in BC studies. We reported that luminal B is the most common BC subtype in a group of H/L and that ERBB2, GRB7 and MIEN1 genes have increased expression in women with higher Indigenous American ancestry. Immune infiltration of tumors has become a hallmark for the prediction of outcome. However, contrary to TNBC, luminal tumors have been considered low immunogenic. Immune infiltration of luminal B tumors in H/L has not yet been investigated. Our goal was to predict immune infiltration of luminal B tumors based on RNA-seq data and according to the levels of body mass index (BMI) and ancestral fractions (West African, European, Indigenous American). Methods: We performed RNA-seq in 70 luminal B tumors of H/L from Puerto Rico. Ancestry was estimated by genotyping on the Affymetrix U.K. Biobank array and global ancestry proportions determined with Admixture Software v1.3, using 1000 Genomes reference population for anchoring. BMI, age at diagnosis and tumor size were extracted from the Electronic Medical Records. We used Partek Flow for the RNA-seq analysis based on ancestry fraction and BMI. Prediction of cell populations was done in xCell. Correlation analysis was done in GraphPad Prism v7.05. Results: We found an inverse correlation between Indigenous American and γδ-T cell infiltration (R2= -0.3; p=0.03) while BMI was associated with increased infiltration of basophils (R2=0.3; p=0.026). Among women with high BMI, those with low European ancestry had increased levels of basophils infiltration R2=0.66; p=0.17) and those with high European ancestry had reduced infiltration of naïve CD8+ T cells (R2= -0.53; p=0.008) and reduced plasmacytoid dendritic cells (pDC, R2=-0.51; p=0.01). Conclusions: We found that luminal B tumors have infiltration of immune cells that may contribute to differences in the response to treatment and outcome. To the best of our knowledge, the role of infiltrating basophils into breast cancer tissues has not been described. However, circulating basophils and predicted infiltration of basophils into ovarian and colorectal cancer tissues have been correlated with survival. Our findings have to be confirmed in a larger set of samples and by additional methods, including immunohistochemistry. Citation Format: Jone Garai, Julie Dutil, Douglas W. Cress, Victoria Seewaldt, Jamie K. Teer, Laura Fejerman, Lucio Miele, Jovanny Zabaleta. Cell infiltration prediction of breast cancer tissues identifies basophils as potentially important immune cells in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2729.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-2729
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    Abstract 1497: miRNA expression analysis in high-risk HPV-positive cervical scrapes for the detection of cervical disease
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 1497-1497
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 1497-1497
    Abstract: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Persistent infections with high-risk HPV (hrHPV) genotypes can lead to high-grade lesions (Cervical Intraepithelial Neoplasia Grade 2 or higher, CIN2+), that if left untreated progress to cancer. hrHPV test has high sensitivity to detect CIN2+, but it has low specificity because close to 90% of women spontaneously clear the infection. Biomarkers to stratify hrHPV+ women with cervical lesions that may progress to cancer are needed. miRNAs are small noncoding RNAs that regulate gene expression, can be detected in cervical scrapes, and are differentially expressed between high- and low-grade lesions. Aim To identify miRNAs differentially expressed between CIN3+ and ≤CIN1 lesions and evaluate their potential use as biomarkers to distinguish CIN3+ in hrHPV+ women. Methods We used miRNAseq to compare miRNAs expression patterns in cervical scrapes of hrHPV+ women: 35 with low-grade lesions (NEG= 26; CIN1= 9) and 36 with high-grade lesions (CIN3= 32; SCC= 4). The samples were collected through the ASCUS-COL Trial in Medellin, Colombia. Women with low- or high-grade cervical lesions exhibit similar sociodemographic characteristics (Chi-square p-values & gt;0.05). The RNAseq data were processed in GeneGlobe-QIAGEN, which incorporates cut-adapt, bowtie and DeSEq2. Receiver Operating Characteristic (ROC) analyses with a 95% confidence interval of Area Under the Curve (AUC) were made to evaluate the diagnostic accuracy of each miRNA differentially expressed, to detect CIN3+. Multivariate Logistic Regression Analysis using normalized counts of mapped reads identified a combination of the differentially expressed miRNAs that best predicted CIN3+. We identified putative pathways using MetaCore. Results An average of & gt;9 million reads by sample and around 3.5 million reads mapped to miRBase V21 was obtained. The principal component analysis did not show factors that could introduce bias to differential gene expression analysis. We identified 38 miRNAs differentially expressed. Compared to & lt;CIN1 lesions, 9 miRNAs were overexpressed and 29 underexpressed in CIN3+ lesions. Six miRNAs presented AUC & gt;0.60 (p-value & lt;0.05) to detect CIN3+. The best predictive combination of 9 miRNAs exhibits an AUC of 0.89, 95% CI (0.83 - 0.97), of which 4 were overexpressed and 5 underexpressed in CIN3+ vs & lt;CIN1. Interestingly, 5 miRNAs underexpressed in CIN3+, target VEGF, a known angiogenic mediator linked to malignancy. Conclusion We identified miRNAs differentially expressed with good diagnostic performance to distinguish high- from low-grade lesions in cervical scrapes samples. Further validation on a larger cohort of cervical scrapes samples is needed to confirm the potential role of these miRNAs to triage hrHPV+ women. Citation Format: Martha Isabel González Ramírez, Samuel Agudelo, Maria Cecilia Agudelo, Jone Garai, Li Li, Carlos Alberto Orozco Castaño, Jovanny Zabaleta, Gloria Inés Sánchez Vásquez. miRNA expression analysis in high-risk HPV-positive cervical scrapes for the detection of cervical disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1497.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-1497
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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