Characterization of the Intra-tumoral B Cell Immunoglobulin Repertoire Is of Prognostic Value for Esophageal Squamous Cell Carcinoma.
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ABSTRACT:
SUBMITTER: Wang Z
PROVIDER: S-EPMC9257635 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAbsent in melanoma 1-like (AIM1L), also known as crystalline beta gamma domain containing 2. The relationship between AIM1L and tumors has not been fully investigated, and the biological function of AIM1L in different tumors is unknown, so we bioinformatically explored a possible relationship between AIM1L and esophageal squamous cell carcinoma (ESCC).MethodsAIM1L mRNA expression was detected by the Gene Expression Omnibus database (GSE20347, GSE161533, and GSE53625), and protein level expression was detected by immunohistochemistry. The correlation between AIM1L expression and clinical pathological characteristics was evaluated by the Wilcoxon signed rank test or chi-square test. Kaplan-Meier analysis and Cox proportional risk regression model were used to determine the prognostic value of AIM1L in ESCC patients and establish and verify a nomogram. Find genes highly related to the expression of AIM1L, conduct GO and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and conduct GSEA analysis on the gene set. The "CIBERSORT" R package was used to explore the relationship between AIM1L and immune infiltration, and the "OncoPredict" R package was used to explore the relationship between AIM1L and drug sensitivity.ResultsCompared with the matched adjacent non-cancer tissues, the expression of AIM1L was down-regulated in ESCC tissues, and correlated with tumor grade. Kaplan-Meier survival analysis and Cox analysis showed that the low expression of AIM1L was related to the poor prognosis of ESCC patients. Enrichment analysis explained the possible function of AIM1L, GSEA determined the highly correlated signal pathway of AIM1L low expression phenotype, immune infiltration analysis determined that AIM1L was related to activated NK cells and macrophage M2, and drug sensitivity analysis determined that the low expression of AIM1L might be related to EGFR targeted drug resistance.ConclusionAIM1L may be a candidate tumor suppressor gene for ESCC and an independent molecular biomarker for the prognosis of ESCC patients.
| S-EPMC10470706 | biostudies-literature
Project description:BackgroundThe aim of this study was to identify prognostic long non-coding RNAs (lncRNAs) and develop a multi-lncRNA signature for suvival prediction in esophageal squamous cell carcinoma (ESCC).MethodsThe clinical and gene expression data from Gene Expression Omnibus database (GSE53624, n = 119) were obtianed as training set. A total of 98 paired ESCC tumor and normal tissues were detected by RNA sequencing and used as test set. Another 84 ESCC tissues were used for real-time quantitative PCR(qRT-PCR) and as an independent validation cohort. Survival analysis, Cox regression and Kaplan-Meier analysis were performed.ResultsWe screened a prognostic marker of ESCC from the GSE53624 dataset and named it as the five-lncRNA signature including AC007179.1, MORF4L2-AS1, RP11-488I20.9, RP13-30A9.2, RP4-735C1.6, which could classify patients into high- and low-risk groups with significantly different survival(median survival: 1.75 years vs. 4.01 years, log rank P < 0.05). Then test dataset and validation dataset confirmed that the five-lncRNA signature can determine the prognosis of ESCC patients. Predictive independence of the prognostic marker was proved by multivariable Cox regression analyses in the three datasets (P < 0.05). In addition, the signature was found to be better than TNM stage in terms of prognosis.ConclusionThe five-lncRNA signature could be a good prognostic biomarker for ESCC patients and has important clinical value.
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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.
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Project description:Accumulated evidence has shown that the programmed cell death receptor 1/programmed cell death receptor 1 ligand 1 (PD-1/PD-L1) pathway is a promising therapeutic target for cancer immunotherapy. However, the association between PD-L1 and esophageal squamous cell carcinoma (ESCC) patient survival remains unclear. We performed a meta-analysis to investigate the prognostic value of PD-L1 in ESCC. We searched PubMed, Embase, Web of Knowledge, and Cochrane Central Register of Controlled Trials databases for relevant studies that evaluated PD-L1 expression and ESCC patient survival. Fixed- and random-effects meta-analyses were conducted according to the heterogeneity of the included studies. Sensitivity analysis was performed according to Metan-based influence analysis. Publication bias was evaluated using Egger's and Begg's tests. Overall, 13 studies with 2,877 patients were included. Twelve studies demonstrated the association between overall survival (OS), and 6 studies described the relation between disease-free survival (DFS). PD-L1 overexpression was found in 43.7% (1,258 of 2,877) of the patients with ESCC. High PD-L1 expression was associated with distant metastasis in patients with ESCC (P = 0.04). Moreover, high PD-L1 expression was significantly associated with poor OS (hazard ratio [HR] 1.38, 95% confidence interval [CI] = 1.02-1.86, P = 0.04) and especially in Asian populations (HR 1.49, 95% CI = 1.11-1.99, P = 0.008). But it did not have an impact on disease-free survival (HR 1.15, 95% CI = 0.76-1.74, P = 0.52). Further well-designed clinical studies with uniform assessment approaches for PD-L1 expression are warranted to verify its prognostic value.
| S-EPMC5862626 | biostudies-literature
Project description:BackgroundPrecisely forecasting the prognosis of esophageal squamous cell carcinoma (ESCC) patients is a formidable challenge. Cuproptosis has been implicated in ESCC pathogenesis; however, the prognostic value of cuproptosis-associated long noncoding RNAs (CuRLs) in ESCC is unclear.MethodsTranscriptomic and clinical data related to ESCC were sourced from The Cancer Genome Atlas (TCGA). Using coexpression and Cox regression analysis to identify prognostically significant CuRLs, a prognostic signature was created. Nomogram models were established by incorporating the risk score and clinical characteristics. Tumor Immune Dysfunction and Rejection (TIDE) scores were derived by conducting an immune landscape analysis and evaluating the tumor mutational burden (TMB). Drug sensitivity analysis was performed to explore the underlying molecular mechanisms and guide clinical dosing.ResultsOur risk score based on 5 CuRLs accurately predicted poorer prognosis in high-risk ESCC patients across almost all subgroups. The nomogram that included the risk score provided more precise prognostic predictions. Immune pathways, such as the B-cell receptor signaling pathway, were enriched in the datasets from high-risk patients. High TMB in high-risk patients indicated a relatively poor prognosis. High-risk patients with lower TIDE scores were found to benefit more from immunotherapy. High-risk patients exhibited greater responsiveness to Nilotinib, BI-2536, P22077, Zoledronate, and Fulvestrant, as revealed by drug sensitivity analysis. Real-time PCR validation demonstrated significant differential expression of four CuRLs between ESCC and normal cell lines.ConclusionsThe above risk score and nomogram can accurately predict prognosis in ESCC patients and provide guidance for chemotherapy and immunotherapy.
| S-EPMC10599721 | biostudies-literature
Project description:Background: The peripheral benzodiazepine receptor (PBR) has previously been reported as an oncogene in prostate, breast and colorectal cancers, but its prognostic value, biological behavior and function in esophageal squamous cell carcinoma (ESCC) has not been investigated. Methods: qRT-PCR, western blotting and immunohistochemistry (IHC) were used to detect PBR expression in ESCC and matched non-cancerous tissues. Based on all of the significantly independent factors, a nomogram was established to predict the prognosis of ESCC patients. In addition, we performed comprehensive in vitro experiments to study the functions of PBR in cell growth, colony formation, and migration ability, as well as its relationship with epithelial-mesenchymal transition (EMT) related proteins in ESCC cells. Results: The mRNA and protein expression levels of PBR in ESCC were higher than those in adjacent non-tumor esophageal epithelial tissues. The IHC results demonstrated that PBR expression was an independent prognostic factor in ESCC survival, patients with higher PBR expression had a poorer survival than those with low expression, and PBR expression was significantly associated with lymphoid nodal status. Furthermore, a nomogram was established to reliably predict the probability of death in ESCC patients, with a Harrell's c-index of 0.696. In the vitro experiments, knocking down the expression of PBR inhibited proliferation, colony formation and migration of ESCC cells, and regulated EMT-associated proteins (up-regulation of E-cadherin, ZO-1 and β-catenin and concomitant with down-regulation of Fibronectin and N-cadherin). Conclusions: PBR is an independent prognostic factor in ESCC, and it promotes ESCC progression and metastasis. Basing on PBR expression level, a nomogram is established and performs a well in predicting survival of ESCC patients.
| S-EPMC5665051 | biostudies-literature
Project description:Background: Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological type of esophageal cancer, but there is a lack of definite prognostic markers for this cancer. Methods: We used the ESTIMATE algorithm to access the tumor microenvironment (TME) of ESCC cases deposited in the TCGA database, and identified TME-related prognostic genes using Cox regression analysis. A least absolute shrinkage and selector operation or LASSO algorithm was used to identify key prognostic genes. Risk scores were calculated, and a clinical predictive model was constructed to evaluate the prognostic value of TME-related genes. Results: We found that high immune and stromal scores were significantly associated with poor overall survival (p < 0.05). We identified a total of 1,151 TME-related differently expression genes, among which 67 were prognosis-related genes. Through the LASSO method, 13 key prognostic genes were selected, namely, ADAMTS16, LOC51089, CH25H, CORO2B, DLGAP1, GYS2, HAL, MXRA8, NPTX1, OTX1, RET, SLC24A2, and SPI1, and a 13-gene risk score was constructed. A higher score was indicative of a poorer prognosis than a lower risk score (hazard ratio = 8.21, 95% confidence interval: 2.56-26.31; P < 0.001). The risk score was significantly correlated with immune/stromal scores and various types of infiltrating immune cells, including CD8 cells, regulatory T cells, and resting macrophages. Conclusion: We characterized the tumor microenvironment in ESCC, and identified the key prognosis genes. The risk score based on the expression profiles of these genes is proposed as an indicator of TME status and is instrumental in predicting patient prognosis.
| S-EPMC7767869 | biostudies-literature
Project description:BackgroundEsophageal squamous cell carcinoma was treated by operation and chemoradiotherapy. However, the prognosis of most patients is poor after treatment, and most studies have shown that FGF2 and its receptor (FGFR) are involved in the development of various malignant tumors. FGF2 plays an important role in tumor progression and malignancy. In this study, the immunohistochemistry of FGF2, FGFR3, and FGFBP1 was used to further verify the expression of the three proteins in 172 patients with esophageal squamous cell carcinoma (ESCC) who had not received preoperative chemoradiotherapy and its effect on the prognosis of ESCC.Methods(1) χ 2 test was used to analyze the relationship between proteins and clinicopathological parameters. Survival analysis was used to investigate the effect of three proteins on prognosis. (2) Paired sample t-test was used to analyze the mRNA expression of the three proteins in fresh ESCC tissues and adjacent normal tissues.ResultsFGF2 was correlated with tumor size (p = 0.026), gender (p = 0.047), and lymph metastasis (p = 0.007) in ESCC tissues. The high expression of FGFR3 was associated with tumor differentiation (p = 0.043 and p < 0.05), lymph node metastasis (p = 0.078 and p < 0.1), and race (p = 0.033 and p < 0.05). The high expression of FGFBP1 was significantly associated with the degree of tumor differentiation (p = 0.012), age (p = 0.045), and lymph node metastasis (p = 0.032) of ESCC patients. The expression of FGF2, FGFR3, and FGFBP1-mRNA in ESCC tissues was significantly higher than that in adjacent tissues (p < 0.001, p < 0.001, and p = 0.001). Patients with high expression of FGF2, FGFBP1, and FGFR3 had poor prognosis. There was a weak positive correlation between FGF2 and FGFBP1, as well as FGFR.ConclusionThe FGF2-FGFR3 axis may promote the progression of esophageal squamous cell carcinoma. The FGF2-FGFR3 axis may be a new direction of targeted therapy for esophageal squamous cell carcinoma. FGF2 and FGFR3 may be used as prognostic markers of esophageal squamous cell carcinoma.
| S-EPMC7748917 | biostudies-literature
Project description:Stromal cell-derived factor-1α (SDF-1α) is a chemokine that has been reported to be involved in tumor progression in several malignancies. This study aimed to evaluate the crucial role of SDF-1α in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. A total of 169 patients with ESCC were identified, including overexpression of SDF-1α in 60 patients and low expression of SDF-1α in 109 patients by immunohistochemical analysis. Two ESCC cell lines, TE1 and KYSE30, were selected to evaluate the tumor cell proliferative effect of SDF-1α. Univariate and multivariate analyses showed that high tumor (T) status, positive lymph node metastasis, tumors located in the upper esophagus, and SDF-1α overexpression were significantly related to worse disease-free survival and overall survival. In addition, the two cell lines were treated with SDF-1α, AMD3100 (an SDF-1α-ligand receptor antagonist), and chemotherapeutic agents (cisplatin). Our in vitro study results showed that SDF-1α promoted the proliferation of tumor cells, and blocking the SDF-1α pathway displayed a growth inhibition effect in a dose-dependent manner. SDF-1α plays an important role in the progression of ESCC and is an independent prognostic factor for ESCC patients who underwent esophagectomy.
| S-EPMC7281421 | biostudies-literature
Project description:BackgroundThe current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC).MethodsA total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC.Results & discussionThe 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was.ConclusionThe tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.
| S-EPMC5289103 | biostudies-literature