Circulating microRNAs as potential biomarkers in triple-negative breast cancer: a translational research study of the NACATRINE trial.

Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter® Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.

Gene expression alterations predict the pathological complete response in triple-negative breast cancer exploratory analysis of the NACATRINE trial.

This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve [AUC], 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.

The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high-grade cervical lesion detection in liquid-based cytology.

BACKGROUND: Some studies reported that differential gene expression could be used as a biomarker for high-grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid-based cytology (LBC) samples. METHODS: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer-related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from

Interleukin-8 and Interleukin-6 Are Biomarkers of Poor Prognosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor microenvironment play crucial roles in ESCC development and metastasis, thus influencing therapy efficiency. As such, cytokines are the most prominent targets for specific therapies and prognostic parameters to predict tumor progression and aggressiveness. In this work, we examined the association between ESCC progression and the systemic levels of inflammatory cytokines to determine their usefulness as diagnostic biomarkers. We analyzed the levels of IL-1ß, IL-6, IL-8, IL-10, TNF-α e IL-12p70 in a group of 70 ESCC patients and 70 healthy individuals using Cytometric Bead Array (CBA) technology. We detected increased levels of IL-1ß, IL-6, IL-8, and IL-10 in ESCC patients compared to controls. However, multivariate analysis revealed that only IL8 was an independent prognostic factor for ESCC, as were the well-known risk factors: alcohol consumption, tobacco usage, and exposure to pesticides/insecticides. Importantly, patients with low IL-6, IL-8, TNM I/II, or those who underwent surgery had a significantly higher overall survival rate. We also studied cultured Kyse-30 and Kyse-410 cells in mice. We determined that the ESCC cell line Kyse-30 grew more aggressively than the Kyse-410 cell line. This enhanced growth was associated with the recruitment/accumulation of intratumoral polymorphonuclear leukocytes. In conclusion, our data suggest IL-8 as a valuable prognostic factor with potential as a biomarker for ESCC.

MicroRNA­130a­3p inhibition suppresses cervical cancer cell progression.

MicroRNAs (miRNAs or miRs) play essential roles in the initiation and progression of human tumors, including cervical cancer. However, the mechanisms underlying their actions in cervical cancer remain unclear. The present study aimed to evaluate the functional role of miR­130a­3p in cervical cancer. Cervical cancer cells were transfected with a miRNA inhibitor (anti­miR­130a­3p) and a negative control. Adhesion­independent cell proliferation, migration and invasion were evaluated. The findings presented herein demonstrated that miR­130a­3p was overexpressed in HeLa, SiHa, CaSki, C­4I and HCB­514 cervical cancer cells. The inhibition of miR­130a­3p significantly reduced the proliferation, migration and invasion of cervical cancer cells. The canonical delta­like Notch1 ligand (DLL1) was identified as a possible direct target of miR­103a­3p. The DLL1 gene was further found to be significantly downregulated in cervical cancer tissues. On the whole, the present study demonstrates that miR­130a­3p contributes to the proliferation, migration and invasion of cervical cancer cells. Therefore, miR­130a­3p may be used as a biomarker to determine cervical cancer progression.

Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer.

Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.

Molecular Biomarkers Predict Pathological Complete Response of Neoadjuvant Chemotherapy in Breast Cancer Patients: Review.

Neoadjuvant chemotherapy (NAC) is often used to treat locally advanced disease for tumor downstaging, thus improving the chances of breast-conserving surgery. From the NAC response, it is possible to obtain prognostic information as patients may reach a pathological complete response (pCR). Those who do might have significant advantages in terms of survival rates. Breast cancer (BC) is a heterogeneous disease that requires personalized treatment strategies. The development of targeted therapies depends on identifying biomarkers that can be used to assess treatment efficacy as well as the discovery of new and more accurate therapeutic agents. With the development of new "OMICS" technologies, i.e., genomics, transcriptomics, and proteomics, among others, the discovery of new biomarkers is increasingly being used in the context of clinical practice, bringing us closer to personalized management of BC treatment. The aim of this review is to compile the main biomarkers that predict pCR in BC after NAC.

A Systematic Review of MicroRNAs Involved in Cervical Cancer Progression.

To obtain a better understanding on the role of microRNAs in the progression of cervical cancer, a systematic review was performed to analyze cervical cancer microRNA studies. We provide an overview of the studies investigating microRNA expression in relation to cervical cancer (CC) progression, highlighting their common outcomes and target gene interactions according to the regulatory pathways. To achieve this, we systematically searched through PubMed MEDLINE, EMBASE, and Google Scholar for all articles between April 2010 and April 2020, in accordance with the PICO acronym (participants, interventions, comparisons, outcomes). From 27 published reports, totaling 1721 cases and 1361 noncancerous control tissue samples, 26 differentially expressed microRNAs (DEmiRNAs) were identified in different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer development. It was identified that some of the dysregulated microRNAs were associated with specific stages of cervical cancer development. The results indicated that DEmiRNAs in different stages of cervical cancer were functionally involved in several key hallmarks of cancer, such as evading growth suppressors, enabling replicative immortality, activation of invasion and metastasis, resisting cell death, and sustained proliferative signaling. These dysregulated microRNAs could play an important role in cervical cancer's development. Some of the stage-specific microRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cervical cancer.

miRNA expression profiling of hereditary breast tumors from BRCA1- and BRCA2-germline mutation carriers in Brazil.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues. METHODS: Global miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1- and BRCA2- mutation carriers (n = 5) and non-mutation carriers (n = 3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis. RESULTS: miRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: > 2.0 and p < 0.05) and considered as potential biomarkers (area under the curve > 0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways. CONCLUSIONS: Our results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2- germline mutations and may be useful for future clinical management.

Identification and performance evaluation of housekeeping genes for microRNA expression normalization by reverse transcription-quantitative PCR using liquid-based cervical cytology samples.

Screening for cervical cancer by cytology has been effective in reducing the worldwide incidence and mortality rates of this disease. However, a number of studies have demonstrated that the sensitivity of conventional cervical cytology may be too low for detection of cervical intraepithelial neoplasias (CIN). Therefore, it is important to incorporate more sensitive molecular diagnostic tests that could substantially improve the detection rates and accuracy for identifying CIN lesions. MicroRNAs (miRNAs) are a class of small non-coding RNAs with the potential to provide robust non-invasive cancer biomarkers for detecting CIN lesions in liquid-based cervical cytology (LBC) samples. At present, there is no consensus on which are the best housekeeping genes for miRNA normalization in LBC. The present study aimed to identify housekeeping genes with consistent and reproducible performance for normalization of reverse transcription-quantitative PCR (RT-qPCR) expression analysis of miRNA using LBC samples. The present study firstly selected six potential candidate housekeeping genes based on a systematic literature evaluation. Subsequently, the expression levels of microRNAs U6, RNU-44, RNU-47, RNU-48, RNU-49 and hsa-miR-16 were measured in 40 LBC samples using RT-qPCR. The stability of each potential housekeeping gene was assessed using the NormFinder algorithm. The results revealed that U6 and RNU-49 were the most stable genes among all candidates requiring fewer amplification cycles and smaller variation across the sample set. However, RNU-44, RNU-47, RNU-48 and hsa-miR-16 stability exceeded the recommended housekeeping value suitable for normalization. The findings revealed that U6 may be a reliable housekeeping gene for normalization of miRNA RT-qPCR expression analysis using LBC samples.

Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer.

OBJECTIVES: The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia. METHODS: A total of 447 cervical cytology samples obtained from women who underwent colposcopy were examined. The cases were distributed as follows: (1) cervices without cervical intraepithelial neoplasia (CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern for a panel of 15 genes was analysed by quantitative methylation-specific PCR (qMSP) and compared between the groups (≤CIN 1 vs. CIN 2+). RESULTS: In the validation set, seven genes presented significantly different methylation profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and specificity (86.7% and 61.3%, respectively) similar to that of the HPV test (91.3% and 50.0%, respectively). The independent factors associated with the diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR = 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr-HPV (odds ratio [OR] = 5.5). CONCLUSIONS: Hypermethylation of the hsa-miR-124-2, SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in cervical cancer regardless of the hr-HPV status.