Clinical significance of signal regulatory protein alpha (SIRPα) expression in esophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Koga N
PROVIDER: S-EPMC8353899 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RAR?. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RAR? in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RAR? expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC.
| S-EPMC5076458 | biostudies-literature
Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a subtype of esophageal cancer with high incidence and mortality. Due to the poor 5-year survival rates of patients with ESCC, exploring novel diagnostic markers for early ESCC is emergent. Collagen, the abundant constituent of extracellular matrix, plays a critical role in tumor growth and epithelial-mesenchymal transition. However, the clinical significance of collagen genes in ESCC has been rarely studied. In this work, we systematically analyzed the gene expression of whole collagen family in ESCC, aiming to search for ideal biomarkers.MethodsClinical data and gene expression profiles of ESCC patients were collected from The Cancer Genome Atlas and the gene expression omnibus databases. Bioinformatics methods, including differential expression analysis, survival analysis, gene sets enrichment analysis (GSEA) and co-expression network analysis, were performed to investigate the correlation between the expression patterns of 44 collagen family genes and the development of ESCC.ResultsA total of 22 genes of collagen family were identified as differentially expressed genes in both the two datasets. Among them, COL1A1, COL10A1 and COL11A1 were particularly up-regulated in ESCC tissues compared to normal controls, while COL4A4, COL6A5 and COL14A1 were notably down-regulated. Besides, patients with low COL6A5 expression or high COL18A1 expression showed poor survival. In addition, a 7-gene prediction model was established based on collagen gene expression to predict patient survival, which had better predictive accuracy than the tumor-node-metastasis staging based model. Finally, GSEA results suggested that collagen genes might be tightly associated with PI3K/Akt/mTOR pathway, p53 pathway, apoptosis, cell cycle, etc.ConclusionSeveral collagen genes could be potential diagnostic and prognostic biomarkers for ESCC. Moreover, a novel 7-gene prediction model is probably useful for predicting survival outcomes of ESCC patients. These findings may facilitate early detection of ESCC and help improves prognosis of the patients.
| S-EPMC6779144 | biostudies-literature
Project description:Backgroundc-Met, one of current potential hot targets, has been suggested as a potential tumor marker in the development of esophageal squamous cell carcinoma (ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal squamous cell carcinoma in four phase II trials who had tumor tissues from archival in our center and analyze the correlations between c-Met expression and clinical features.MethodsNinety patients with advanced ESCC who were admitted to the phase II clinical trials in the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute from March 2007 to March 2014 were finally eligible for present study and the corresponding tissues and clinical data were collected. The expression of c-Met in the tissue samples was detected by immunohistochemistry (IHC). c-Met overexpression was defined as ≥ the median value of H-score. Kaplan-Meier and Cox multivariate regression were conducted to evaluate the relationship between c-Met expression and ESCC survival.ResultsThe overexpression of c-Met is 43.3% in advanced ESCC. There was no statistical difference between c-Met expression and clinical features except sex and tumor location. Survival analysis documented that the overexpression of c-Met predicted a worse prognosis (OS: 253 d vs 422 d, P = 0.011). In the group treated with chemotherapy combined with anti-EGFR drugs, patients with lowexpression of c-Met had a better OS than those with overexpression of c-Met (OS: 577 d vs 232 d, P = 0.007).Conclusionsc-Met may be an independent prognostic factor in advanced ESCC. The overexpression of c-Met may predict a worse efficacy of anti-EGFR therapy.
| S-EPMC4307685 | biostudies-literature
Project description:BackgroundCD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers.MethodsWe studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR).ResultsPathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018).ConclusionsThis study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.
| S-EPMC3599647 | biostudies-literature
Project description:The present study analyzed the expression of the histone deacetylase (HDAC) 1, 2 and 3 in primary esophageal squamous cell carcinoma (ESCC) samples and how their levels correlate with clinicopathological parameters. ESCC patients (n=88) in the present study had received no previous treatment before undergoing surgical excision. The mRNA expression of HDAC1, -2 and -3 were detected by semi-quantified PCR in ESCC samples and distal normal samples. The relationship of HDAC1, -2 and -3 expression with clinicopathological parameters was analyzed by ?2 test. The correlation among these HDACs was analyzed by Pearson's correlation test. Compared with distal normal tissues, ESCC samples had higher expression of HDAC1, but not HDAC2 or HDAC3 (P<0.05). The expression of HDACs was different between Kazak and Han ethnicities. The expression of HDAC2 was correlated with invasion depth (P<0.05), but not with sex, age, metastasis, or the degree of tumor differentiation (P>0.05). There was no association between HDAC1 or HDAC3 and clinicopathological parameters (P>0.05). For the Kazak and Han ethnicities, HDAC1 expression was present in male patients, patients with well/moderate differentiated ESCC and T3 and T4 ESCC (P<0.01). HDAC1 in patients aged <60 was associated with ethnicity (P<0.05). HDAC2 expression was different in positive LN metastasis, well/moderate differentiation and T3 and T4 ESCC (P<0.01). HDAC3 expression in male patients, patients with negative LN metastasis and well/moderate differentiation ESCC was associated with ethnicity (P<0.05). Additionally, the expression levels of HDAC1, -2 and -3 did not correlate with each other. Thus, HDAC1 expression may be used as a risk factor for ESCC and HDAC2 levels may be used to predict invasion depth. The expression of HDAC1, -2 and -3 has ethnic differences.
| S-EPMC7282189 | biostudies-literature
Project description:ObjectiveMyosin light chain 9 (MYL9) is necessary for cytoskeletal dynamics and experimental metastasis, but its expression in esophageal squamous cell carcinoma (ESCC) has not been addressed. We investigated the expression pattern and clinical significance of MYL9 in patients with ESCC.MethodsWe examined MYL9 expression using quantitative real-time PCR and western blotting in NE1 immortalized esophageal epithelial cells, ESCC cell lines, and paired ESCC tissues. MYL9 protein in 136 primary ESCC tissues and other types of solid tumor was detected using immunohistochemistry. The association between MYL9 expression and clinical parameters and survival was evaluated by statistical analysis.ResultsMYL9 was significantly upregulated in the ESCC cell lines as compared with NE1 cells. In the paired ESCC samples, MYL9 mRNA and protein expression was not significantly different between lesion tissues and the matched adjacent noncancerous tissues. In ESCC tissue, both intratumoral and peritumoral stroma were positive for MYL9. In the 136 ESCC samples, high MYL9 expression in the tumor cells significantly correlated with histological differentiation (p = 0.028), recurrence (p = 0.01), and vital status (p < 0.01). Patients with high MYL9 expression in the tumor cells had poorer overall survival (OS) and recurrence-free survival. Multivariate analysis revealed that high MYL9 expression in tumor cells was an independent and significant risk factor affecting OS after curative treatment (hazard ratio = 2.254, 95% confidence interval = 1.347-3.771, p = 0.002).ConclusionsMYL9 expression might be a promising prognostic marker and therapeutic target in ESCC.
| S-EPMC5384754 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, we collected eight pairs of ESCC samples and corresponding adjacent normal esophageal tissues for RNA-seq from eight ESCC patients underwent radical resection of EC. None of these ESCC patients received preoperative chemotherapy or radiotherapy.The tissue samples were stored at -80°C immediately after resection. These 8 patients included 6 males and 2 females with a median age of 60 years. RNA-seq was executed by Wuhan Seqhealth Technology Co.LTD. TRIzol reagent (Invitrogen, Carlsbad, CA, USA) was applied to extract and prepare total RNA from tumors and paired adjacent non-ESCC tissues. A total amount of 3 μg RNA per sample was used as initial material for the RNA sample preparations. Nanodrop™ 1000 spectrophotometer was applied to examined RNA purity. RNA concentration was determined using a Qubit® 3.0 Fluorometer. RNA integrity was determined using an RNA Nano 6000 Assay Kit and a Bioanalyzer 2100 system. Afterward, the sequencing libraries were established using the NEBNext Ultra Directional RNA Library Prep Kit for Illumina base on manufacturer’s protocols. The 200 Illumina HiSeq X Ten platform was used to sequence the libraries. RNA sequencing reads were aligned to the reference of homo_sapiens.GRCh38. In the current study, we obtained the data on log2 (x + 0.001) conversion level 3 and reported RNA-seq data in transcripts per kilobase million (TPM).
2021-01-17 | GSE164158 | GEO
Project description:This study was aimed to assess serum microRNA-30d-5p (miR-30d-5p) expression in patients with esophageal squamous cell carcinoma before and after operation, exploring its associations with clinical pathological parameters. A total of 30 esophageal cancer patients who underwent radical resection and were pathologically confirmed with esophageal squamous cell carcinoma in the First Affiliated Hospital of Anhui Medical University, from April to May in 2013, were enrolled, alongside 19 healthy controls. The expression levels of miRNA in serum from patients with esophageal squamous cell carcinoma before and after operation were assessed by microarrays and real-time PCR (RT-PCR). The associations of miR-30d-5p expression with clinical pathological parameters were determined. Serum hsa-miR-30d-5p levels in patients with esophageal squamous cell carcinoma (study group) were significantly associated with the tumor depth of invasion, lymph node metastasis, tumor location and length, histopathological type and degree of differentiation, as well as history of smoking and drinking (P<0.05). Moreover, changes of serum miRNA levels were more prominent than that of thymidine kinase 1 (TK1). There were significant differences in hsa-miR-30d-5p expression levels between the study and control groups (P<0.05). These results indicated that microRNA-30d-5p is a potential marker of esophageal squamous cell carcinoma, with high expression having a certain promoting role in the occurrence and development of esophageal cancer.
| S-EPMC6965463 | biostudies-literature
Project description:We previously conducted transcriptome analysis of a paired specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues and found that mRNA expression of cystatin A (CSTA), a member of the cystatin superfamily, was perturbed in tumors compared with that in the background mucosa. However, little is known about the significance of CSTA expression in ESCC.The mRNA expression of CSTA was evaluated by qRT-PCR using 28 paired frozen samples of tumor and nontumor mucosae. The protein expression of CSTA was evaluated by the immunostaining of formalin-fixed, paraffin-embedded sections of ESCC samples from 59 patients who underwent surgery, and its relationship with clinical features was analyzed.The mRNA expression of CSTA was significantly decreased in ESCC compared with that in matched normal mucosa (P < .0001). The protein expression of CSTA was limited in stratum granulosum and stratum spinosum but not in stratum basal in normal esophageal mucosa. It was reduced in all ESCC tissue samples compared with normal tissues; however, CSTA expression levels in tumors showed considerable variation. Of the 59 samples, 20 did not express CSTA, whereas 39 clearly expressed it. The expression of CSTA in tumors was significantly associated with pT classification (deeper tumor invasions) (P = .0118) and advanced TNM stages (P = .0497). In CSTA-positive tumor samples, CSTA-expressing cancer cells often expressed Ki67, a proliferation marker, which was in sharp contrast to normal mucosa, where Ki67-expressing cells were limited to the basal layer and did not express CSTA. Furthermore, CSTA expression was observed in all 22 lymph node metastases analyzed.Relatively high levels of CSTA expression in tumors were correlated with tumor progression and advanced cancer stage, including lymph node metastasis.
| S-EPMC5908574 | biostudies-literature
Project description:The present authors previously identified a novel candidate tumor suppressor gene, zinc finger protein 750 (ZNF750), in esophageal squamous cell carcinoma (ESCC) (1). The present study aimed to clarify the clinical significance of ZNF750 expression in ESCC. The association between ZNF750 DNA mutation status and the mRNA expression was examined by whole exome sequence analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The expression of ZNF750 in 76 patients with ESCC (Kyushu University Beppu Hospital) was measured using immunohistochemistry and RT-qPCR. Using this dataset, the association between ZNF750 mRNA expression and clinicopathological factors was examined. Additionally, survival analysis was performed using datasets from the Kyushu University Beppu Hospital and The Cancer Genome Atlas (TCGA). The biological effects of ZNF750 expression were explored using gene set enrichment analysis (GSEA) and were validated using datasets from the Cancer Cell Line Encyclopedia (CCLE) and the Kyushu University Beppu Hospital. ZNF750 expression analyses demonstrated that ZNF750 mRNA expression was lower in patients with the DNA mutations compared with those without the mutations (P<0.05), and ZNF750 expression was downregulated in tumor tissues compared with normal tissues (P<0.00005). In the clinicopathological analysis, the low ZNF750 expression group exhibited a higher incidence of undifferentiated histology (P<0.05) compared with the high expression group. The low ZNF750 expression group exhibited a poorer prognosis in the Kyushu and TCGA datasets (P<0.0005 and P<0.05, respectively). GSEA indicated that ZNF750 expression was significantly correlated with epithelial differentiation in ESCC. This was confirmed using the datasets from CCLE and the Kyushu University Beppu Hospital by analyzing the levels of small proline rich protein 1A mRNA, an epithelial differentiation-associated gene. In conclusion, the results of the present study suggested that ZNF750 serves a role as a tumor suppressor; potentially via regulating epithelial differentiation and that it may be a promising biomarker of poor outcomes in ESCC.
| S-EPMC5529940 | biostudies-literature