Prostate cancer (PCa) is the leading cause of cancer-related death in men. This pathology is complex and heterogeneous; therefore, elucidating the molecular mechanisms that lead to its origin and ...progression is imperative. MicroRNAs (miRNAs or miRs) are part of the epigenetic machinery that regulates the expression of human genes, therefore, mutations in the genes that encode them can lead to a dysregulation in their expression, which directly impacts their target genes, which could be oncogenes or tumor suppressor genes. In PCa several dysregulated expression levels of miRNAs are associated with perturbed cellular processes. A differential expression of miRNAs such as miR-145-5p and miR-148-3p has been observed in PCa, possibly due to mutations in regions near the miRNAs. However, the molecular mechanisms that lead to the dysregulation of these miRNAs still need to be clarified. Therefore, the present study aimed to analyze the expression of miRNAs and their relationship with mutations in patients with and without PCa. In total, 71 patients were analyzed: 41 of whom had PCa (CAP group) and 30 with benign pathology (BPD group). Underexpression was observed in miR-145-5p and miR-148b-3p in PCa patients (P=0.03 and P=0.001, respectively). In miR-145-5p, no mutations related to its expression were identified. For miR-148b-3p, a set of mutations were identified in the chr12:54337042/54337043 region, which were grouped into the mutation named DelsAAG. Although this mutation's abnormal allele is related to PCa (P=0.017), a statistically significant difference was observed in the expression of miR-148b-3p between carriers and non-carriers of the mutated allele, identifying a mechanism likely to be involved in the miR-148b-3p dysregulation.
Abstract
Background and aims
There is a link between genetics with metabolic balance and adiposity homeostasis on metabolic syndrome (MetS). Polymorphism in adipokine genes such as leptin and ...adiponectin may play an important role in its development. This study aimed to determine the association of the individual and general components of MetS with genetic alterations in
LEP
(rs7799039 and rs2167270) and
ADIPOQ
(rs1501299 and rs2241766) genes in the Mexican population.
Methods and results
The polymorphisms of the
LEP
gene rs7799039 and rs2167270, together with rs1501299 and rs2241766 polymorphisms of the
ADIPOQ
gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 328 individuals (n = 131 MetS). The rs7799039 under the recessive inheritance model was found to be associated with increased risk of MetS (OR = 2.16, 95% CI = 1.06–4.37), dyslipidemia (OR = 7.97, 95% CI = 2.17–29.36), low HDL (OR = 7.01, 95% CI = 1.65–29.71) and hypertension (OR = 13.02, 95% CI = 1.76–96.44); the heterozygote demonstrate a protective effect on MetS (OR = 0.48, 95% CI = 0.28–0.88) and diabetes (OR = 0.09, 95% CI = 0.02–0.53) under the over the dominant model. Haplotype analysis showed linkage disequilibrium between the SNPs of
ADIPOQ
rs1501299/rs2241766, and their association as risk factors for low HDL and hypertension.
Conclusion
The association of rs7799039 with the presence of MetS, suggests a risk factor for the development of dyslipidemia, as well as its heterozygous as a protective factor for DM. There is a linkage disequilibrium between the SNPs of
ADIPOQ.
Prostate cancer (PCa) is one of the leading causes of death among men. Genes such as PCA3, PSA, and Fra-1 are suggested to serve as potential tools for the detection of PCa, as they are deregulated ...during this pathology. A similar event occurs with small non-coding RNAs, called miRNAs, specifically miR-195-5p, miR-133a-3p, and miR-148b-3p, which were analyzed in a Chinese population and suggested to be possible candidates for PCa diagnosis. We evaluated the expression levels of three miRNAs and three genes in tissue samples of PCa and benign prostate disease, such as benign prostatic hyperplasia, or prostatitis, in order to determine their potential as candidates for PCa detection. Our results showed a statistically significant overexpression of 279-fold increase in PSA levels and a 1,012-fold increase in PCA3 levels in PCa patients compared to benign prostate disease patients (p = 0.001 and p = 0.002, respectively). We observed a positive correlation between the expression of miR-148b-3p and the expression of PSA and PCA3 genes, two established biomarkers in PCa. The expression of miR-148b-3p was not related to clinical characteristics, such as age and weight, as observed for the other miRNAs analyzed, suggesting its potential as a biomarker for detection of this pathology.
Prostate cancer (PCa) is the second most frequent cancer diagnosed in men worldwide. The detection methods for PCa are either unreliable, like prostate-specific antigen (PSA), or extremely invasive, ...such as in the case of biopsies. Therefore, there is an urgent necessity for reliable and less invasive detection procedures that can differentiate between patients with benign diseases and those with cancer. In this matter, microRNAs (miRNAs) are suggested as potential biomarkers for cancer. MiRNAs have been found to be dysregulated in several different cancers, and these genetic alterations may present specific signatures for a given malignancy. Here, we examined the expression of miR141-3p, miR145-5p, miR146a-5p, and miR148b-3p in human tissue samples of PCa (n = 41) and benign prostatic diseases (BPD) (n = 30) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We combined the expression results with patient clinicopathological characteristics in logistic regression models to create accurate PCa predictive models. A model including information of miR148b-3p and patient age showed relevant prediction results (area under the curve AUC = 0.818, precision = 0.763, specificity = 0.762, and accuracy = 0.762). A model including all four miRNAs and patient age presented outstanding prediction results (AUC = 0.918, precision = 0.861, specificity = 0.861, and accuracy = 0.857). Our results represent a potential novel procedure based on logistic regression models that utilize miRNA expressions and patient age to assist with PCa diagnosis.
Background and aims There is a link between genetics with metabolic balance and adiposity homeostasis on metabolic syndrome (MetS). Polymorphism in adipokine genes such as leptin and adiponectin may ...play an important role in its development. This study aimed to determine the association of the individual and general components of MetS with genetic alterations in LEP (rs7799039 and rs2167270) and ADIPOQ (rs1501299 and rs2241766) genes in the Mexican population. Methods and results The polymorphisms of the LEP gene rs7799039 and rs2167270, together with rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 328 individuals (n = 131 MetS). The rs7799039 under the recessive inheritance model was found to be associated with increased risk of MetS (OR = 2.16, 95% CI = 1.06-4.37), dyslipidemia (OR = 7.97, 95% CI = 2.17-29.36), low HDL (OR = 7.01, 95% CI = 1.65-29.71) and hypertension (OR = 13.02, 95% CI = 1.76-96.44); the heterozygote demonstrate a protective effect on MetS (OR = 0.48, 95% CI = 0.28-0.88) and diabetes (OR = 0.09, 95% CI = 0.02-0.53) under the over the dominant model. Haplotype analysis showed linkage disequilibrium between the SNPs of ADIPOQ rs1501299/rs2241766, and their association as risk factors for low HDL and hypertension. Conclusion The association of rs7799039 with the presence of MetS, suggests a risk factor for the development of dyslipidemia, as well as its heterozygous as a protective factor for DM. There is a linkage disequilibrium between the SNPs of ADIPOQ. Keywords: Metabolic syndrome, LEP, ADIPOQ, Haplotype
Concomitant trisomy 2q3 and monosomy 4q3 have been rarely reported. Pure trisomy 2q3 has been associated with microcephaly, hypertelorism, low-set ears, micrognathia, visceral abnormalities, and ...growth retardation. Monosomy 4q3 includes a wide variety of dysmorphic features such an abnormal skull shape, hypertelorism, Pierre Robin sequence, short nose with abnormal bridge, fifth finger clinodactyly, congenital heart, and genitourinary defects, in addition to intellectual disability, developmental delay, and hypotonia, but more distal deletions involving 4q34-qter may result in milder phenotypes. Here, we present a child with a mild dysmorphic syndrome, resulted of a duplication 2q34-qter and a deletion 4q35.2-qter inherited of his father.
We report a child, who at birth presented hypotonia, dysmorphism, and bilateral cryptorchidism. At 2 years and 9 month of age he showed brachycephaly, narrow forehead, bilateral frontoparietal hypertrichosis, down slanting palpebral fissures, sparse eyebrows, sparse short eyelashes, hypertelorism, depressed nasal root, broad nasal bridge, bulbous nasal tip, prominent colummela, broad nasal ala, smooth filtrum, high arched palate, thin upper lips, and ears rotated backwards. He also showed telethelia, hypertrichosis from dorsal to the sacral region, hands with clinodactyly and hypoplasia of the terminal phalanx of the fifth finger, and broad thumbs, broad first toes, and right cryptorchidism. A chromosomal study revealed a karyotype 46,XY,der(4)t(2;4)(q34;q35.2), while an array comparative genomic hybridization showed a 31.12 Mb duplication of the chromosome 2q34-q37.3 and a 1.49 Mb deletion in the chromosome 4q35.2.
To our knowledge, only four families with translocation t(2;4) have been reported, two of them involving t(2q;4q), but the breakpoints involved in our patient have not been previously observed. The genomic imbalance in this patient was a duplication of 318 genes of the region 2q34-q37.3 and a deletion of 7 genes of 4q35.2. We discuss difficulty to assign specific congenital abnormalities to these duplicated/deleted regions and include some cases with terminal deletions of 4q with normal or just mildly detectable phenotypic effects.
Thyroid nodules are the main indicators of thyroid cancer, their malignancy is evaluated by cytological analysis and imaging technology, however, there are still cases where the result is not enough ...to classify thyroid cancer. Therefore, there is a necessity for accurate molecular biomarkers to collaborate in the diagnosis. Here, we analyzed the mRNA relative expression of CLDN1, TIMP1, and KRT19 genes in FNA of malignant (n = 48) and benign (n = 49) thyroid nodules by RT-qPCR analysis to assess their predictive value as cancer biomarkers. We identified a significant overexpression of the three transcripts in malignant nodules, therefore, the evaluation of their predictive capacity to distinguish between benign and malignant nodule as individual biomarkers were evaluated by logistic regression tests, obtaining promising prediction results to rule out cancer; later by random forest to create a stronger model, we included expression results with clinicopathological characteristics, the best model consists of the three-mRNA level expression with patient's history of cancer (AUC = 0.821, accuracy = 85.4% and sensitivity of 81.1%). These results demonstrate a dysregulated expression of CLDN1, KRT19 and TIMP1 in thyroid cancer, thus, represent a promising panel of biomarkers to be evaluated in indeterminate thyroid nodules.
•CLDN1, KRT19 and TIMP1 were significantly overexpressed in malignant thyroid nodules.•Strong correlation may suggest functional interactions during cancer progression.•High predictive value to rule out cancer as individual biomarkers.
Abstract Thyroid carcinoma is the most prevalent endocrine neoplasm. The most recurrent mutation in thyroid cancer (TC) is the V600E substitution in BRAF, which induces the over-activation of the ...MAPK pathway. The interaction between this pathway and the deregulation of genes that facilitate tumorigenesis such as CLDN1 could be useful for decision-making related to surgical removal and the degree of initial resection; however, there is a lack of information on the association of CLDN1 expression with BRAF V600E. Objective. Evaluate the gene expression of CLDN1 in BRAF-mutated and BRAF-unmutated thyroid nodules. Methods. RT-qPCR was performed to assess BRAF genotyping (rs113488022) and CLDN1 expression in 94 thyroid nodule biopsy samples (TC=48). Clinicopathological data was retrieved to establish further associations. Results. Mutated BRAF thyroid nodules were found to be 7.14 ± 0.293 times more expressed than those without the mutation (p < 0.001, N=94). BRAF V600E mutation was identified in patients with TC exclusively. CLDN1 expression was 41.315 ± 0.554 times greater in patients with TC than in those without TC (p < 0.001). Heterozygous patients had a change factor of 6.8, whereas mutated homozygotes had a change factor of 7.5 (p < 0.001, N=94). CLDN1 mean expression is significantly higher in A allele carriers compared to normal homozygotes (p < 0.001). When analyzing just within the TC group, the behavior is maintained, suggesting a potential association between the mutated allele and the expression of these genes. Conclusion. CLDN1 is significantly upregulated in TC patients carrying the BRAF V600E mutation. BRAF V600E is only observed in patients with TC, implying a biological connection between them, which can be explained via MAPK; subsequent studies are needed to confirm the correlations. Citation Format: Andrea Ross Orozco, Eliakym Arámbula Meraz, Anette Roxana Gastelum Quiroz, Fred Luque Ortega, Edith Eunice García Alvarez, Marco Álvarez Arrazola, Karla Lizbeth Morales Hernández, Noemí García Magallanes. BRAF V600E is associated with the upregulation of CLDN1 in thyroid cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB050.
Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes ...have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with (n=27) and without (n=20) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples (p=0.005 and p=0.001, respectively) and in high-aggressiveness BCa (p=0.026 and p=0.037, respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B (p=0.005) and S-WT (p=0.011), and in the same manner, ADIPOQ was negatively related with these two survivin variants (p=0.001 and p=0.005, respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.
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