B Cell Lymphocytes as a Potential Source of Breast Carcinoma Marker Candidates
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ABSTRACT:
SUBMITTER: Tkacikova S
PROVIDER: S-EPMC11242293 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:Laryngeal squamous cell carcinoma is a very common in head and neck cancer, accounting for 25% of all cases, with high mortality rates and poor prognosis. In this study, we compared expression profiles of clinical samples from15 larynx tumors and 10 non-neoplastic larynx tissue using a custom-built cDNA microarray containing 332 probes for 285 genes previously identified as up- or down-regulated in head and neck tumors by the Head and Neck Annotation Consortium (Reis et al., Cancer Res 65:1693-99, 2005). Thirty-five genes showed statistically significant differences (SNR ≥|1.0|,p-value ≤ 0.001) in expression between tumor and non-tumor larynx tissue samples. Functional annotation indicated that these genes are involved in cellular processes relevant to the cancer phenotype, such as apoptosis, cell cycle, DNA repair, proteolysis, protease inhibition, signal transduction, and transcription regulation. Six of the identified transcripts map to intronic regions of protein-coding genes and may comprise unannotated exons or yet uncharacterized long ncRNAs with a regulatory role in the gene expression program of larynx tissue. Differential expression of 10 of these genes (ADCY6, AES, AL2SCR3, CRR9, CSTB, DUSP1, MAP3K5, PLAT, UBL1 and ZNF706) was independently confirmed by quantitative real-time RT-PCR. Among these, the CSTB gene product has cysteine protease inhibitor activity that has been associated to an antimetastatic function. Interestingly, CSTB showed low expression in all tumor samples analyzed (p-value < 0.0001). The set of genes identified here contribute to a better understanding of the molecular basis of larynx cancer, and at the same time provide novel candidate markers for improving diagnosis, prognosis and treatment of this carcinoma. Keywords: Gene expression profiling of larynx tumors and non-neoplastic adjacent tissue
2009-06-22 | GSE10288 | GEO
Project description:Larynx squamous cell carcinoma (LSCC) is the second most aggressive cancer from head and neck (HSCC). Survival of LSCC patients has been found worsening, albeit significant advances in technology and therapeutics were made. We sought to clarify new genetic targets driven the development of LSCC. Analyzing tumors revealed that eight members of the homeobox gene family (HOX) were expressed 200 times more in LSCC samples than in normal larynx tissue. qPCR analysis validated all transcriptomic findings for the HOX gene family. Receiver Operating Characteristic statistical method (ROC curve) predicted that 8 members of the HOX gene family differentiate tumors from their normal surrounding tissue. Enabling the comparison of patient clinics with gene expression data, ROC curve analysis yet revealed that HOXC8 and HOXD11 genes are related to the tumor differentiation degree and regional lymph node metastasis, respectively. From siRNA assay, we found that HOXC8 and HOXD11 genes are essential for the expansion of FADU cell colonies. Our findings strongly suggest that members of the HOX family might be associated with the development of LSCC. Twenty nine cancer samples and thirteen margin samples were collected from patients undergoing surgical ablation of LSCC according to Ethic Committee guideline and patient pre-informed signed consents. Whole human genome microarray analysis was applied to investigate new genetic targets in LSCC.
2014-12-25 | E-GEOD-59102 | biostudies-arrayexpress
Project description:Larynx squamous cell carcinoma (LSCC) is the second most aggressive cancer from head and neck (HSCC). Survival of LSCC patients has been found worsening, albeit significant advances in technology and therapeutics were made. We sought to clarify new genetic targets driven the development of LSCC. Analyzing tumors revealed that eight members of the homeobox gene family (HOX) were expressed 200 times more in LSCC samples than in normal larynx tissue. qPCR analysis validated all transcriptomic findings for the HOX gene family. Receiver Operating Characteristic statistical method (ROC curve) predicted that 8 members of the HOX gene family differentiate tumors from their normal surrounding tissue. Enabling the comparison of patient clinics with gene expression data, ROC curve analysis yet revealed that HOXC8 and HOXD11 genes are related to the tumor differentiation degree and regional lymph node metastasis, respectively. From siRNA assay, we found that HOXC8 and HOXD11 genes are essential for the expansion of FADU cell colonies. Our findings strongly suggest that members of the HOX family might be associated with the development of LSCC.
2014-12-25 | GSE59102 | GEO
Project description:Ovarian cancer is a malignant gynecologic disease rarely diagnosed in the early stages. Among the various types of ovarian cancer, clear cell carcinoma has a poor prognosis due to its malignant potential. MicroRNAs (miRNAs/miRs) regulate gene expression in cells by suppressing the translation of target genes or by degrading the target mRNA. miRNAs are also secreted from the cells in the blood, binding to proteins or lipids and assisting in cell-cell communication. Therefore, serum miRNAs may be considered potential diagnostic biomarkers for ovarian cancer. The present study investigated and identified specific miRNAs associated with ovarian clear cell carcinoma and compared them to those in ovarian endometrioma samples and healthy controls. CA125, an ovarian tumor marker, did not differ between patients with ovarian clear cell carcinoma, endometriosis or healthy controls. Subsequently, four miRNAs (miR-146a-5p, miR-191-5p, miR-484 and miR-574-3p) were analyzed. The expression levels of miR-146a-5p and miR-191-5p were significantly increased in the serum samples from patients with ovarian clear cell carcinoma compared with those in the healthy controls, but there was no significant difference compared with in patients with endometriosis. Furthermore, the bioinformatics analysis showed that CCND2 and NOTCH2 were the candidate target genes of miR-146a-5p and miR-191-5p. In conclusion, the results of the present study demonstrated that miR-146a-5p and miR-191-5p may be useful as early and non-invasive diagnostic tools in ovarian clear cell carcinoma. These miRNAs can help in distinguishing between ovarian clear cell carcinoma and ovarian endometrioma. To the best of our knowledge, no previous studies have screened any candidates specifically for ovarian clear cell carcinoma.
| S-EPMC10804375 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.
| S-EPMC4646358 | biostudies-literature
Project description:ZNF-281 is a zinc finger factor which can lead to cancer progression and metastasis. Its up-regulation reported in many cancers was correlated with metastasis and worsened patients' prognosis. This is the first study describing ZNF-281 in the context of OSCC. Oral tissue samples drawn from 66 OSCC patients and 36 control patients were collected to determine protein (using immunochemistry and the semi-quantitative H-score method) and mRNA expression levels (using the RT-qPCR reaction). Our aim was to assess the ZNF-281 expression level in OSCC and the control group. Moreover, we determined the impact of ZNF-281 on survival parameters and the association of diversified clinical parameters with ZNF-281 expression. Clinical factors such as grade, AJCC stage and radiotherapy have an impact on the ZNF-281 H-score level, whereas AJCC stage and grade have an influence on ZNF-281 mRNA expression. Our survival analysis indicated that the impact on overall survival is not statistically significant, and the prognostic potential of ZNF-281 is rather limited. Our findings show that both levels of the ZNF-281 H-score and mRNA are decreased in OSCC in comparison to normal tissue. Moreover, we estimated that the H-score can differentiate normal tissue from OSCC with a sensitivity of 97% and specificity of 93.7%.
| S-EPMC8197962 | biostudies-literature
Project description:Ovarian cancer is a malignant gynecologic disease rarely diagnosed in the early stages. Among ovarian cancers, clear cell carcinoma has a poor prognosis due to its malignant potential. MicroRNAs (miRNAs) regulate gene expression in cells by suppressing the translation of the target gene or by degrading the target mRNA. They are also secreted from the cells in the blood, binding to the proteins or lipids and assisting in cell-cell communication. Hence, serum miRNAs can also be diagnostic biomarkers for ovarian cancer. This study investigated and identified specific miRNAs for ovarian clear cell carcinoma and compared them to those of ovarian endometrioma in healthy patients. CA125, an ovarian tumor marker, did not differ between patients with ovarian clear cell carcinoma, endometriosis, or healthy controls. Four miRNAs (miR-146a-5p, miR-191-5p, miR-484, and miR-574-3p) were analyzed. The miR-146a-5p and miR-191-5p expression levels were significantly increased in the serum samples from the patients with ovarian clear cell carcinoma compared to the healthy controls but not in the patients with endometriosis (P < 0.05). Furthermore, the bioinformatics analysis showed that CCND2 and NOTCH2 were the candidate target genes of miR 146a-5p and miR-191-5p. In conclusion, our results showed that miR 146a-5p and miR-191-5p might be useful as early and non-invasive diagnostic tools in ovarian clear cell carcinoma. These miRNAs can help in distinguishing between ovarian clear cell carcinoma and ovarian endometrioma. To the best of our knowledge, no studies have screened any candidates specifically for clear cell carcinoma.
2023-10-06 | GSE239685 | GEO
Project description:The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients.Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR.SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432).In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.
| S-EPMC3038979 | biostudies-literature
Project description:BackgroundEpigenetic mechanisms play vital roles in the activation, differentiation, and effector function of immune cells. The breast and kidney-expressed chemokine (CXCL14) mainly contributes to the regulation of immune cells. However, its role in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in renal cell carcinoma (RCC).ObjectivesThis study aimed to elucidate the role of CXCL14 in predicting the efficacy of immunotherapy in patients with RCC.MethodsCXCL14 expression and RNA-sequencing, single-cell RNA-sequencing (scRNA-seq), and survival datasets of RCC from public databases were analyzed, and survival was compared between different CXCL14 levels. The correlation between CXCL14 and immune infiltration and human leukocyte antigen (HLA) gene expression was analyzed with TIMER2.0 and gene expression profiling interactive analysis. Institutional scRNA-seq and immunohistochemical staining analyses were used to verify the relationship between CXCL14 expression level and the efficacy of immunotherapy.ResultsCXCL14 was expressed in fibroblast and malignant cells in RCC, and higher expression was associated with better survival. Enrichment analysis revealed that CXCL14 is involved in immune activation, primarily in antigen procession, antigen presentation, and major histocompatibility complex assemble. CXCL14 expression was positively correlated with T-cell infiltration as well as HLA-related gene expression. Among the RCC cohort receiving nivolumab in Checkmate 025, the patients with CXCL14 high expression had better overall survival than those with CXCL14 low expression after immunotherapy. scRNA-seq revealed a cluster of CXCL14+ fibroblast in immunotherapy responders. Immunohistochemistry analysis verified that the patients with high CXCL14 expression had an increased proportion of high CD8 expression simultaneously. The expression level of CXCL14 was associated with CXCR4 expression in RCC.ConclusionCXCL14 expression is associated with immunotherapy response in RCC. It is a promising biomarker for immunotherapy response prediction and may be an effective epigenetic modulator in combination with immunotherapy approaches.
| S-EPMC10752123 | biostudies-literature
Project description:BackgroundLeucine-rich repeat-coupled receptor 6 (LGR6) is a marker of the skin, nails, and other types of adult tissue stem cells and has been widely found to be related to the development and progression of a variety of cancer types. The clinical significance and biological function of LGR6 in esophageal squamous cell carcinoma (ESCC) have not been determined.MethodsThe expression of LGR6 at the transcriptional level was analyzed by searching the TCGA and UCSC data sets. Immunohistochemistry, WB, and q-PCR were used to detect the expression of LGR6 in ESCC and adjacent normal tissues. LGR6 PPI networks and KEGG pathways were used to analyze the potential biological functions of LGR6.ResultsThe expression of LGR6 in ESCC tissues was significantly higher than that in normal tissues and was negatively correlated with the differentiation degree of ESCC and the prognosis of the patients but not closely correlated with the TNM stage of ESCC. PPI networks showed that LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4. KEGG pathway analysis showed that LGR6 activated the Wnt/β-catenin signaling pathway by binding with RSPO ligands to promote the progression of ESCC.ConclusionLGR6 can serve as a potential diagnostic and prognostic marker for ESCC.
| S-EPMC7171331 | biostudies-literature