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8 pages, 268 KiB

Open AccessCommunication

Impact of pri-let-7a-1 rs10739971 for Gastric Cancer Predisposition in an Amazon Region

by Roberta Borges Andrade, Amanda de Nazaré Cohen-Paes, Diana Feio da Veiga Borges Leal, Karla Beatriz Cardias Cereja Pantoja, Laura Patrícia Albarello Gellen, Darlen Cardoso de Carvalho, Tatiane Piedade de Souza, Marianne Rodrigues Fernandes, Paulo Pimentel de Assumpcão, Rommel Mario Rodríguez Burbano, Sidney Emanuel Batista dos Santos and Ney Pereira Carneiro dos Santos

Genes 2023, 14(2), 453; https://doi.org/10.3390/genes14020453 - 9 Feb 2023

Cited by 1 | Viewed by 1142

Abstract

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates [...] Read more.

Gastric cancer (GC) is the fifth most common type of cancer and the fourth leading cause of cancer death. In Brazil, GC has a high incidence and mortality rates, and it is highly variable by region. The Amazon region has significant rising rates among all Brazil regions. Only very few studies have evaluated the association between genetic variants and the risk of gastric cancer in the Brazilian Amazon population. Therefore, this study aimed to investigate associations between single nucleotide polymorphisms of miRNA processing genes and the risk for GC in this population. Potentially functional single nucleotide polymorphisms from miRNA processing genes were genotyped in 159 cases and 193 healthy controls by QuantStudio Real Time PCR. According to our findings, the genotype GG of the variant rs10739971 presents a lower risk to the development of GC in comparison to the remaining genotypes (p = 0.000016; OR = 0.055; 95% CI = 0.015–0.206). This is the first study to report the association of pri-let-7a-1 rs10739971 with GC in the Brazilian Amazon population, which is a highly mixed population with a unique genetic constitution that is different from other populations that are studied in the vast majority of scientific research. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

18 pages, 2583 KiB

Open AccessArticle

Proposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasms

by Tabatha Gutierrez Prieto, Camila Machado Baldavira, Juliana Machado-Rugolo, Eloisa Helena Ribeiro Olivieri, Eduardo Caetano Abilio da Silva, Alexandre Muxfeldt Ab’ Saber, Teresa Yae Takagaki and Vera Luiza Capelozzi

Genes 2022, 13(12), 2309; https://doi.org/10.3390/genes13122309 - 7 Dec 2022

Viewed by 1566

Abstract

Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological [...] Read more.

Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians’ decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (MAP1B, SNAI2, MMP2, WNT5A) are also involved in neurological diseases, in brain metastasis, and interact with platinum-based chemotherapy and tyrosine–kinase inhibitors. Collectively, these findings emerge as an important ancillary tool to improve the strategies of histologic diagnosis in PNENs and unveil the four EMT genes that can play an important role in driving chemical response in PNENs. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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18 pages, 3873 KiB

Open AccessArticle

Prognosis Risk Model Based on Necroptosis-Related Signature for Bladder Cancer

by Zhenghao Chen, Rui Cao, Ren Wang, Yichuan Wang, Donghao Shang and Ye Tian

Genes 2022, 13(11), 2120; https://doi.org/10.3390/genes13112120 - 15 Nov 2022

Viewed by 1440

Abstract

Background: Bladder cancer(BLCA) is the ninth most common cancer. In recent years, necroptosis was found to be related to the occurrence and development of tumors. In this study, we aimed to construct a model based on a necroptosis-related signature to evaluate the potential [...] Read more.

Background: Bladder cancer(BLCA) is the ninth most common cancer. In recent years, necroptosis was found to be related to the occurrence and development of tumors. In this study, we aimed to construct a model based on a necroptosis-related signature to evaluate the potential prognostic application in BLCA. Methods: A total of 67 necroptosis-related genes were used to select the ideal cluster numbers, and it was found that there were four necroptosis-related patterns. Then, we compared the gene expression levels among all of the groups and established a necroptosis-related prognostic model. We made the following enrichment analysis of function and built a novel scoring system, the NEC score, to evaluate the state of necroptosis according to the expression level of necroptosis-related genes. Results: A total of 67 necroptosis-related genes were used to define four distinct necroptosis-related patterns: NEC cluster1–4. Each NEC cluster exhibited different patterns of survival and immune infiltration. Based on univariate Cox regression analyses and least absolute shrinkage and selection operator (Lasso) regression, 14 necroptosis-related genes were established to develop the NEC score. Patients were divided into two groups based on the NEC score. Patients in the high NEC score group had a significantly poorer overall survival than those in the low NEC score group. We further confirmed the correlation of clinical characteristics, as well as the immunotherapy outcome, with the NEC score, and confirmed the potential of the NEC score to be an independent prognostic factor. Furthermore, we compared the expression levels of eight potential biomarker genes between our own BLCA tissues and para-carcinoma tissue. Conclusion: We developed a novel NEC score that has a potential prognostic value in BLCA patients and may help personalized immunotherapy counselling. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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16 pages, 1177 KiB

Open AccessArticle

Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors

by Laila C. Schenkel, Joseph Mathew, Hal Hirte, John Provias, Guillaume Paré, Michael Chong, Daria Grafodatskaya and Elizabeth McCready

Genes 2022, 13(11), 2075; https://doi.org/10.3390/genes13112075 - 9 Nov 2022

Cited by 3 | Viewed by 1764

Abstract

Molecular biomarkers, such as IDH1/IDH2 mutations and 1p19q co-deletion, are included in the histopathological and clinical criteria currently used to diagnose and classify gliomas. IDH1/IDH2 mutation is a common feature of gliomas and is associated with a glioma-CpG island methylator phenotype (CIMP). Aberrant [...] Read more.

Molecular biomarkers, such as IDH1/IDH2 mutations and 1p19q co-deletion, are included in the histopathological and clinical criteria currently used to diagnose and classify gliomas. IDH1/IDH2 mutation is a common feature of gliomas and is associated with a glioma-CpG island methylator phenotype (CIMP). Aberrant genomic methylation patterns can also be used to extrapolate information about copy number variation in a tumor. This project’s goal was to assess the feasibility of DNA methylation array for the simultaneous detection of glioma biomarkers as a more effective testing strategy compared to existing single analyte tests. Methods: Whole-genome methylation array (WGMA) testing was performed using 48 glioma DNA samples to detect methylation aberrations and chromosomal gains and losses. The analyzed samples include 39 tumors in the discovery cohort and 9 tumors in the replication cohort. Methylation profiles for each sample were correlated with IDH1 p.R132G mutation, immunohistochemistry (IHC), and previous 1p19q clinical testing to assess the sensitivity and specificity of the WGMA assay for the detection of these variants. Results: We developed a DNA methylation signature to specifically distinguish a IDH1/IDH2 mutant tumor from normal samples. This signature is composed of 11 CpG sites that were significantly hypermethylated in the IDH1/IDH2 mutant group. Copy number analysis using WGMA data was able to identify five of five positive samples for 1p19q co-deletion and was concordant for all negative samples. Conclusions: The DNA methylation signature presented here has the potential to refine the utility of WGMA to predict IDH1/IDH2 mutation status of gliomas, thus improving diagnostic yield and efficiency of laboratory testing compared to single analyte IDH1/IDH2 or 1p19q tests. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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17 pages, 5432 KiB

Open AccessArticle

An Integrated Study on the Differential Expression of the FOX Gene Family in Cancer and Their Response to Chemotherapy Drugs

by Haimeng Yin, Xing Fan, Yanqiao Zhang, Nan Zhao, Xiaoyi Zhao, Kehan Yin and Yali Zhang

Genes 2022, 13(10), 1754; https://doi.org/10.3390/genes13101754 - 28 Sep 2022

Cited by 4 | Viewed by 1927

Abstract

The Forkhead-box (FOX) transcription factors, as one of the largest gene families in humans, play key roles in cancer. Although studies have suggested that several FOX transcription factors have a significant impact on cancer, the functions of most of the FOX [...] Read more.

The Forkhead-box (FOX) transcription factors, as one of the largest gene families in humans, play key roles in cancer. Although studies have suggested that several FOX transcription factors have a significant impact on cancer, the functions of most of the FOX genes in cancer remain elusive. In the study, the expression of 43 FOX genes in 63 kinds of cancer diseases (including many subtypes of same cancer) and in response to 60 chemical substances was obtained from the Gene Expression Atlas database of the European Bioinformatics Institute. Based on the high degree of overlap in FOXO family members differentially expressed in various cancers and their particular responses to chemotherapeutic drugs, our data disclosed the FOX genes that played an important role in the development and progression of cancer. More importantly, we predicted the role of one or several combinatorial FOX genes in the diagnosis and prognostic assessment of a specific cancer and evaluated the potential of a certain anticancer drug therapy for this type of cancer by integrating patterns of FOX genes expression with anticancer drugs sensitivity. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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15 pages, 2981 KiB

Open AccessArticle

Prognostic, Clinicopathological, and Function of Key Cuproptosis Regulator FDX1 in Clear Cell Renal Cell Carcinoma

by Song Zeng, He Zhang, Di Zhang, Xiaopeng Hu and Liming Song

Genes 2022, 13(10), 1725; https://doi.org/10.3390/genes13101725 - 26 Sep 2022

Cited by 3 | Viewed by 2087

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer. Cuproptosis is suggested to be a novel therapy target for cancer treatment. However, the function of cuproptosis and its key regulator FDX1 in ccRCC remains unclear. In this [...] Read more.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer. Cuproptosis is suggested to be a novel therapy target for cancer treatment. However, the function of cuproptosis and its key regulator FDX1 in ccRCC remains unclear. In this study, we adequately explored the prognostic factors, clinicopathological characteristics, and function of FDX1 in ccRCC. We found that the expression of FDX1 was significantly downregulated in ccRCC samples. Patients with a higher FDX1 expression had a significantly better prognosis, including overall survival (OS) (Hazard ratio (HR): 2.54, 95% confidence interval (CI): 1.82–3.53, p < 0.001), disease-specific survival (DSS) (HR: 3.04, 95% CI: 2.04–4.54, p < 0.001), and progression-free survival (PFS) (HR: 2.54, 95% CI: 1.82–3.53, p < 0.001). FDX1 was a clinical predictor to stratify patients into the high or low risk of poor survival, independent of conventional clinical features, with the area under the ROC curve (AUC) of 0.658, 0.677, and 0.656 for predicting the 5-year OS, DSS, and PFS. The nomogram model based on FDX1 had greater predictive power than other individual prognostic parameters. FDX1 mainly participated in the oxidative-related process and mitochondrial respiration-related processes but was not associated with immune infiltration levels. In conclusion, the cuproptosis key regulator FDX1 could serve as a potential novel prognostic biomarker for ccRCC patients. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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12 pages, 987 KiB

Open AccessArticle

Examining the Diagnostic Yield of Tumour Testing and Qualifying Germline Concordance for Hereditary Cancer Variants in Patients with High-Grade Serous Carcinoma

by Emily A. Goebel, Jennifer Kerkhof, Oleksandra Dzyubak, C. Meg McLachlin, Jacob McGee and Bekim Sadikovic

Genes 2022, 13(8), 1398; https://doi.org/10.3390/genes13081398 - 6 Aug 2022

Cited by 1 | Viewed by 1527

Abstract

Despite advances in treatment, prognosis for most patients with high-grade serous carcinoma (HGSC) remains poor. Genomic alterations in the homologous recombination (HR) pathway are used for cancer risk assessment and render tumours sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPi), which [...] Read more.

Despite advances in treatment, prognosis for most patients with high-grade serous carcinoma (HGSC) remains poor. Genomic alterations in the homologous recombination (HR) pathway are used for cancer risk assessment and render tumours sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPi), which can be associated with more favourable outcomes. In addition to patients with tumours containing BRCA1 or BRCA2 pathologic variants, there is emerging evidence that patients with tumours harbouring pathologic variants in other HR genes may also benefit from PARPi therapy. The objective of this study is to assess the feasibility of primary-tumour testing by examining the concordance of variant detection between germline and tumour-variant status using a custom hereditary cancer gene panel (HCP). From April 2019 to November 2020, HCP variant testing was performed on 146 HGSC formalin-fixed, paraffin-embedded tissue samples using next-generation sequencing. Of those, 78 patients also underwent HCP germline testing using blood samples. A pathogenic variant was detected in 41.1% (60/146) of tumours tested, with 68.3% (41/60) having either a BRCA1 or BRCA2 variant (n = 36), or BRCA1/2 plus a second variant (n = 5), and 31.2% (19/60) carrying a pathogenic variant in another HCP gene. The overall variant rate among the paired germline and tumour samples was 43.6% (34/78), with the remaining 56% (44/78) having no pathogenic variant detected in the germline or tumour. The overall BRCA1/2 variant rate for paired samples was 33.3% (26/78), with germline variants detected in 11.5% (9/78). A non-BRCA1/2 germline variant in another HCP gene was detected in 9.0% (7/78). All germline variants were detected in the tumour, demonstrating 100% concordance. These data provide evidence supporting the feasibility of primary-tumour testing for detecting germline and somatic variants in HCP genes in patients with HGSC, which can be used to guide clinical decision-making, and may provide opportunity for improving patient triage and clinical genetic referral practices. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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9 pages, 1396 KiB

Open AccessArticle

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer

by Giovana Miranda Vieira, Laura Patrícia Albarello Gellen, Diana Feio da Veiga Borges Leal, Lucas Favacho Pastana, Lui Wallacy Morikawa Souza Vinagre, Vitória Teixeira Aquino, Marianne Rodrigues Fernandes, Paulo Pimentel de Assumpção, Rommel Mario Rodríguez Burbano, Sidney Emanuel Batista dos Santos and Ney Pereira Carneiro dos Santos

Genes 2022, 13(6), 1039; https://doi.org/10.3390/genes13061039 - 10 Jun 2022

Cited by 8 | Viewed by 2390

Abstract

Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the [...] Read more.

Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the susceptibility and severity of this neoplasm in different populations. Eighty-four genetic variants associated with prostate cancer susceptibility were selected from the literature through genome association studies (GWAS). Allele frequencies were obtained from the 1000 Genomes Project, and epidemiological data were obtained from Surveillance, Epidemiology, and End Results (SEER). The PCa incidence, mortality rates, and allele frequencies of variants were evaluated by Pearson’s correlation. Our study demonstrated that 12 SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs6983267, rs11649743, rs2075110, rs114798100, rs855723, and rs2075109) were correlated with epidemiological data in different ethnic groups. Ten SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs11649743, rs2075110, rs114798100, and rs2075109) were positively correlated with the mortality rate. Seven SNPs (rs1048169, rs2961144, rs7000448, rs4430796, rs2066827, rs12500426, and rs114798100) were positively correlated with incidence. Positive correlations of incidence and mortality rates were more frequent in the African population. The genetic variants investigated here are likely to predispose to PCa and could play a role in its progression and aggressiveness. This genetic study demonstrated here is promising for implementing personalized strategies to screen for prostate cancer in diverse populations. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Solid Tumors)

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