Bone Marrow Stromal Cells Promotes Morphological Senescence of Prostate Cancer Cells and Inhibits Metastasis Associated 1 Gene Level

This study assessed the mechanism of Bone Marrow Stromal Cells (BMSCs) in prostate cancer (PC) and its effect on MTA-1 gene and PC cell senescence. PC-3 cells were assigned into QL group (prostate cancer group: normal culture) and GS group (BMSCs group: treated with BMSCs) followed by analysis of MTA-1 level, cell senescence, apoptosis and invasion. MTA-1 level in QL group (0.83±0.07) was significantly higher than GS group (0.14±0.02) (P < 0.05), indicating that BMSCs had an inhibitory effect on MTA-1 expression. Similar change of MTA-l mRNA was also found with higher level in QL group than GS group (P < 0.05). Cell senescence was found in QS group but not QL group, indicating that BMSCs promote cell senescence. Compared with GS group, QL group has a higher cell number in G0/G1 (67.13±6.45%) and S (19.59±3.35%) than GS group (G0/G1:50.51±2.19% and S: 11.42±1.61%) but lower G2/M (QL: 15.97±3.59% versus GS: 32.25±3.24%). QL group had significantly lower cell apoptosis rate at 35 h (5.21±1.2%) and 45 h (3.97±0.95%) than GS group at 35 h (17.85±1.23%), 45 h (10.21±1.26%) with elevated number of invasions. In conclusion, BMSCs promote PC-3 cell senescence and apoptosis by inhibiting the expression of MTA-1 and reduce cell invasion ability.

Comprehensive Comparative Molecular Characterization of Young and Old Lung Cancer Patients

BackgroundYoung lung cancer as a small subgroup of lung cancer has not been fully studied. Most of the previous studies focused on the clinicopathological features, but studies of molecular characteristics are still few and limited. Here, we explore the characteristics of prognosis and variation in young lung cancer patients with NSCLC.MethodsA total of 5639 young lung cancer samples (NSCLC, age ≤40) were screened from the SEER and the same number of the old (NSCLC, age ≥60) were screened by propensity score matching to evaluate the prognosis of two groups. 165 treatment-naïve patients diagnosed with NSCLC were enrolled to explore the molecular feature difference between two age-varying groups. CCLE cell line expression data was used to verify the finding from the cohort of 165 patients.ResultsThe overall survival of the young lung cancer group was significantly better than the old. Germline analysis showed a trend that the young group contained a higher incidence of germline alterations. The TMB of the young group was lower. Meanwhile, the heterogeneity and evolutionary degrees of the young lung cancer group were also lower than the old. The mutation spectrums of two groups exhibited variance with LRP1B, SMARCA4, STK11, FAT2, RBM10, FANCM mutations, EGFR L858R more recurrent in the old group and EML4-ALK fusions, BCL2L11 deletion polymorphism, EGFR 19DEL, 20IN more recurrent in the young group. For the base substitution, the young showed a lower fraction of transversion. Further, we performed a pathway analysis and found the EGFR tyrosine kinase inhibitor resistance pathway enriched in the young lung cancer group, which was validated in gene expression data later.ConclusionsThere were significantly different molecular features of the young lung cancer group. The young lung cancer group had a more simple alteration structure. Alteration spectrums and base substitution types varied between two groups, implying the different pathogenesis. The young lung cancer group had more potential treatment choices. Although young lung patients had better outcomes, there were still adverse factors of them, suggesting that the young group still needs more caution for treatment choice and monitoring after the treatment to further improve the prognosis.

Identification of Molecular Biomarkers and Key Pathways for Esophageal Carcinoma (EsC): A Bioinformatics Approach

Esophageal carcinoma (EsC) is a member of the cancer group that occurs in the esophagus; globally, it is known as one of the fatal malignancies. In this study, we used gene expression analysis to identify molecular biomarkers to propose therapeutic targets for the development of novel drugs. We consider EsC associated four different microarray datasets from the gene expression omnibus database. Statistical analysis is performed using R language and identified a total of 1083 differentially expressed genes (DEGs) in which 380 are overexpressed and 703 are underexpressed. The functional study is performed with the identified DEGs to screen significant Gene Ontology (GO) terms and associated pathways using the Database for Annotation, Visualization, and Integrated Discovery repository (DAVID). The analysis revealed that the overexpressed DEGs are principally connected with the protein export, axon guidance pathway, and the downexpressed DEGs are principally connected with the L13a-mediated translational silencing of ceruloplasmin expression, formation of a pool of free 40S subunits pathway. The STRING database used to collect protein-protein interaction (PPI) network information and visualize it with the Cytoscape software. We found 10 hub genes from the PPI network considering three methods in which the interleukin 6 (IL6) gene is the top in all methods. From the PPI, we found that identified clusters are associated with the complex I biogenesis, ubiquitination and proteasome degradation, signaling by interleukins, and Notch-HLH transcription pathway. The identified biomarkers and pathways may play an important role in the future for developing drugs for the EsC.

PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) AS DIAGNOSTIC BIOMARKER IN PROSTATE CANCER

Objective: This study aimed to compare PSMA expression in both prostate cancer and benign prostate disease. Material & Methods: PSMA antigen expression was examined using polymerase chain reaction (PCR), twenty samples from each prostate cancer and benign prostate group were examined at the Department of Pathology Anatomy, Sardjito General Hospital. The data was analyzed using version 21 of SPSS. Results: The mean PSMA gene expression in benign groups was 13.49 [95% CI: 11.27 – 15.72] and the mean PSMA gene expression in the malignant group was: 25.14 [95% CI: 20.95-29.33], the p-value was <0.01. Using an independent T-test analysis, we found that the increase in PSMA gene expression in the prostate cancer group was statistically significant. Conclusion: The expression of the PSMA gene was correlated with prostate cancer. Increased PSMA gene expression in prostate tissue could be used as a biomarker to diagnose prostate cancer.

Comparative Evaluation of Diagnostic Performance of Circulating free DNA by Conventional vs. Real Time PCR in Gallbladder Cancer

Background: Circulating free DNA (cfDNA) in serum/plasma has been studied as a promising biomarker in various pathologies, including cancer. However, there is no standardized method for the isolation and quantification of serum cfDNA. An effective and reliable method for isolation and quantification is of utmost importance before any clinical decision. The current study compares the conventional and real-time PCR methods to find any differences and concordance in cfDNA levels between the two methods and the diagnostic accuracy of cfDNA by each method. Methods: Serum sample was collected from 67 subjects, including 17 normal healthy individuals (control, n=17), 19 disease controls (cholecystitis, n=19), and 31 Gallbladder cancer patients (cancer, n=31) before any treatment for cfDNA quantification. Results: The cfDNA level did not differ significantly between two methods in both control and cholecystitis groups. In cancer group, cfDNA level was significantly (P < 0.001) different and higher in real time PCR as compared to conventional PCR. There was no significant correlation between two methods in control (r=0.02, P = 0.937), cholecystitis (r=0.10, P = 0.697), cancer (r=-0.08, P = 0.657) and total cases (control + cholecystitis + cancer) (r=0.06, P = 0.622). The diagnostic accuracy of two methods was found similar (P > 0.05) when assessed between control vs. cholecystitis (Z=0.85, P = 0.397), and control vs. total cases (Z=1.35, P = 0.177). However, the diagnostic accuracy of real time PCR was found significantly different and higher as compared to conventional PCR when assessed between control vs. cancer (Z=2.98, P = 0.003), and cholecystitis vs. cancer (Z=4.41, P < 0.001). Conclusion: Quantitative real-time PCR method is of high accuracy, reproducibility, and time-effectiveness. The diagnostic accuracy of real-time PCR was higher compared to conventional PCR.

Incidence of breast cancer and methylation of PCDH gene: a single ratio meta analysis of single rate

IntroductionBreast cancer presents one of the highest rates of prevalence. With the development of genetics and biotechnology, we have learned that the occurrence and development of many cancers are closely related to abnormal gene expression. At present, some pieces of literature have reported that there may be a correlation between the expression of PCDH and the occurrence of breast cancer.Therefore, we selected some loci from PCDH gene to explore the correlation between the methylation of PCDH gene and breast cancer.Material and methodsThis research is a systematic review and critical appraisal, make a meta-analysis of prospective and retrospective cohort study. Research was conducted through computer Science, Wanfang and Chinese knowledge network databases PubMed, Embase and Network. In a literature search, seven cohort studies were identified. This I2 statistic is used to quantify heterogeneity. A fixed effect model was used to synthesize the results. Regression tests of linear funnel plot asymmetry were used to estimate potential publication bias.ResultsThe methylation rate of PCDH gene in breast cancer with lymph node metastasis was 75%, and that in breast cancer without lymph node metastasis was 70%. The methylation rate of PCDH gene was 75% in breast cancer group with high expression of the Ki-67 gene and 71% in breast cancer group with low expression of Ki-67 gene.ConclusionsAccording to previous studies, the positive rate of methylation of PCDH gene in breast cancer tissues is higher than that in adjacent tissues, and there is no obvious statistical difference in the correlation between lymphatic metastasis and Ki-67.

Retrospective Analysis of INRG Clinical and Genomic Factors for 605 Neuroblastomas in Japan: A Report from the Japan Children’s Cancer Group Neuroblastoma Committee (JCCG-JNBSG)

Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age ≥ 18 months, LDH ≥ 1400 U/L, and BP ≥ 7 correlated with lower overall and event-free survival rates (p < 0.05). The genome subgroup GG-P2s (partial chromosome gain/loss type with 1p/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p < 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP ≥ 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.

Comprehensive Analysis of Alteration Landscape and Its Clinical Significance of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Cancers

Background. Mitochondria are the energy factories of cells. The abnormality of mitochondrial energy metabolism pathways is closely related to the occurrence and development of lung cancer. The abnormal genes in mitochondrial energy metabolism pathways might be the novel targets and biomarkers to diagnose and treat lung cancers. Method. Genes in major mitochondrial energy metabolism pathways were obtained from the KEGG database. The transcriptomic, mutation, and clinical data of lung cancers were obtained from The Cancer Genome Atlas (TCGA) database. Genes and clinical biomarkers were mined that affected lung cancer survival. Gene enrichment analysis was performed with ClusterProfiler and the gene set enrichment analysis (GSEA). STRING database and Cytoscape were used for protein-protein interaction (PPI) analysis. The diagnostic biomarker pattern of lung cancer was optimized, and its accuracy was verified with 10-fold cross-validation. The four genes screened by logistic regression model were verified by western blot in 5 pairs of lung cancer specimens collected in hospital. Results. In total, 188 mitochondrial energy metabolism pathway-related genes (MMRGs) were included in this study. GSEA analysis found that MMRGs in the lung cancer group were mainly enriched in the metabolic pathway of oxidative phosphorylation and electron respiratory transport chain compared to the control group. Age did not affect the mutation frequency of MMRGs. Comparative analysis of these 188 MMRGs identified 43 differentially expressed MMRGs (24 upregulated and 19 downregulated) in the lung cancer group compared to the control group. The survival analysis of these 43 differentially expressed MMRGs found that the survival time was better in the low-expressed GAPDHS group than that in the high-expressed GAPDHS group of lung cancers. The advanced age, high expression of GAPDHS, low expressions of ACSBG1 and CYP4A11, and ACOX3 mutation were biomarkers of poor prognosis in lung cancers. PPI analysis showed that proteins such as GAPDH and GAPDHS interacted with many proteins in mitochondrial metabolic pathways. A four-MMRG-signature model ( y = 0.0069 ∗ ACADL − 0.001 ∗ ALDH 18 A 1 − 0.0405 ∗ CPT 1 B + 0.0008 ∗ PPARG − 1.625 ) was established to diagnose lung cancer with the accuracy up to 98.74%, AUC value up to 0.992, and a missed diagnosis rate of only 0.6%. Western blotting showed that ALDH18A1 and CPT1B proteins were significantly overexpressed in the lung cancer group ( p < 0.05 ), and ACADL and PPARG proteins were slightly underexpressed in the lung cancer group ( p < 0.05 ), which were consistent with the results of their corresponding mRNA expressions. Conclusion. Mitochondrial energy metabolism pathway alterations are the important hallmarks of lung cancer. Age did not increase the risk of MMRG mutation. High expression of GAPDHS, low expression of ACSBG1, low expression of CYP4A11, mutated ACOX3, and old age predict a poor prognosis of lung cancer. Four differentially expressed MMRGs (ACADL, ALDH18A1, CPT1B, and PPARG) established a logistic regression model, which could effectively diagnose lung cancer. At the protein level, ALDH18A1 and CPT1B were significantly upregulated, and ACADL and PPARG were slightly underexpressed, in the lung cancer group compared to the control group, which were consistent with the results of their corresponding mRNA expressions.

ANÁLISE DA RETIRADA PARCIAL DO TECIDO MAMÁRIO EM PACIENTES ONCOLÓGICOS

Introdução: O câncer é uma das doenças mais prevalentes no mundo. Todos os anos várias pessoas passam pela cirurgia de mastectomia que visa a retirada do tecido mamário para auxiliar no tratamento oncológico. Objetivos: Revisar o estudo da análise da recorrência de câncer oncológico através da análise do tecido mamário individual. Métodos: Este trabalho trata-se de um revisão de literatura na qual foi feita com base no levantamento de dados através de artigos do National Center for Biotechnology Informations.Resultados: Nota se que durante o tratamento de pacientes oncológicos mamários a necessidade em sua maioria da retirada do tecido mamário, buscando estética do paciente faz se á uma mastectomia que retire o mínimo possível. tornando se cada vez mais comum caso em que os pacientes fazem mastectomia em que a pele ou o mamilo são preservados. Contudo deve-se levar em conta outros aspectos além da estética. A prevalência da eficácia e segurança desses procedimentos, especialmente NSM e mastectomia poupadora de aréola, no tratamento do câncer de mama permanecem questionáveis. Uma revisão recente do Cochrane Breast Cancer Group concluiu que a qualidade das evidências para todos os resultados, incluindo sobrevida global e local livre de doença, foi considerada muito baixa.¹ Embora exista um valor de referência oncologicamente seguro (5 mm) para o retalho cutâneo, na prática clínica e nos exames de imagem, observamos resultados variáveis, como retalhos não homogêneos finos em alguns pontos, mas espessos em outros bem como como visível e grandes quantidades de RBT². A falta de padronização desses procedimentos cirúrgicos e análises de imagem tem impacto significativo na decisão quanto à radioterapia adjuvante (RT) após mastectomias menos radicais. A diferença entre os diferentes níveis entre o resíduo de tecido mamário em pacientes que passaram por cirurgia devido a tratamento oncológico.³ Conclusões: Este trabalho permitiu observar a necessidade da retirada total do tecido mamário, para melhor eficácia no tratamento de câncer.

Are We Missing Something? The Skin Lesions Not Seen in Teledermatology

Background The suspected skin cancer electronic referral pathway was introduced in 2017. It requires general practitioners to add regional, close-up, and dermoscopic images to a lesion-specific referral template for a teledermatologist to review and advise on management. The virtual lesion clinic is a nurse-led clinic used since 2010 to obtain high-quality images for teledermoscopy assessment. A limitation of both services is the absence of a full-body examination. Objective This study aims to evaluate the number of skin cancers missed during teledermatology assessment. Methods This is a retrospective review of skin lesion referrals to dermatology. Suspected skin cancer referrals made in the latter half of 2020 were compared with referrals to the virtual lesion clinic during a similar time period in 2016. Results The study included 481 patients with 548 lesions in the 2020 suspected skin cancer cohort that were matched for age, sex, and ethnicity to 400 patients with 682 lesions in the 2016 virtual lesion clinic cohort. A total of 41 patients underwent subsequent specialist review in the suspected skin cancer cohort compared to 91 in the virtual lesion clinic cohort. A total of 20% of the suspected skin cancer cohort and 24% of the virtual lesion clinic cohort were found to have at least one additional lesion of concern. The majority of these were keratinocytic skin cancers; there were 2 and 0 additional melanomas or melanoma-in-situ, respectively. The virtual lesion clinic nurses identified additional lesions for imaging in 78 of 400 (20%) patients assessed in the virtual lesion clinic. The teledermatologist determined (author AO) that 73% of these additional lesions were malignant. Of the 548 lesions, 10 (2%) in the suspected skin cancer group were rereferred, none of which had a change in diagnosis. Out of 682 lesions, 16 (2%) in the virtual lesion clinic cohort were rereferred, 6 (1%) of which had a change in diagnosis. Conclusions Patients diagnosed with skin cancer often have multiple lesions of concern. Single-lesion teledermoscopy diagnoses have high concordance with in-person evaluation and histology; however, we have shown that in-person examination may reveal other suspicious lesions. The importance of a full-body skin examination should be emphasized to the referrer. Acknowledgments The Waikato Medical Research Foundation provided financial support for the study. Conflicts of Interest None declared.