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Definition and risk factors of early recurrence based on affecting prognosis of esophageal squamous cell carcinoma patients after radical resection.

ABSTRACT: Early recurrence after surgery could affect cancerous patients' prognosis, but the definition of early recurrence and its risk factors for esophageal squamous cell carcinoma (ESCC) patients are still unclear. This study analyzed the clinical data of 468 post-surgery recurrent ESCC patients retrospectively. A minimum p-value approach was used to evaluate the optimal cut-off value of recurrence free survival (RFS) to define early recurrence. Risk factors of early recurrence were developed based on a Cox model. The optimal cut-off value of RFS to distinguish early recurrence was 21 months (p <0.001). Independent risk factors for early recurrence included tumor locations (HR=0.562, p <0.001), pathological T stage (HR=1.829, p <0.001), tumor diameter (HR=1.344, p = 0.039), positive lymph nodes (HR=1.361, p <0.001), and total resected lymph nodes (HR=1.271, p = 044). For the late recurrent patients, there was a much more significant survival advantage for recurrence after concurrent chemoradiotherapy than that after sequential chemoradiotherapy and radiotherapy alone (p = 0.0066). In conclusion, this study defined 21 months of RFS as early recurrence and also identified its risk factors. Concurrent chemoradiotherapy was suggested as preferred post-relapse treatment for late recurrent ESCC patients.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7985560 | biostudies-literature |

REPOSITORIES: biostudies-literature

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ER expression associates with poor prognosis in male lung squamous carcinoma after radical resection.

Project description:BackgroundClinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient.MethodsWe identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay.ResultsTwelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089-4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients' OS after R0 resection (HR = 2.152, p = 0.037).ConclusionERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.

| S-EPMC8456567 | biostudies-literature

Prediction of early recurrence of hepatocellular carcinoma within the Milan criteria after radical resection.

Project description:Approximately 50% hepatocellular carcinoma patients meeting the Milan criteria utilized to develop an improved prognostic model for predicting the recurrence in these patients. Using univariate and multivariate analysis, cytokeratin-19 and glypican-3 expression patterns, tumor number and histological grading from eight putative prognostic factors comprised the risk factor scoring model to predict the tumor recurrence. In the training cohort, the area under roc curve (AUC) value of the model was 0.715 [95% confidence interval (CI) = 0.645-0.786, P<0.001], which was the highest among all the parameters. The performance of the model was assessed using an independent validation cohort, wherein the AUC value was 0.760 (95% CI=0.647-0.874, P<0.001), which was higher than the other factors. The results indicated that model had high performance with adequate discrimination ability. Moreover, it significantly improved the predictive capacity for the recurrence in patients with hepatocellular carcinoma within the Milan criteria after radical resection.

| S-EPMC5609922 | biostudies-literature

Quantitative proteomics analysis of early recurrence/metastasis of huge hepatocellular carcinoma following radical resection.

Project description:BackgroundHepatic resection is the preferred treatment for huge hepatocellular carcinoma (>10 cm in diameter; H-HCC). However, the patients with H-HCC suffer from poor prognosis due to the early recurrence/metastasis. The underlying mechanism of H-HCC's early recurrence/metastasis is currently not well understood.ResultsHere, we describe an Isobaric Tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach to analyze the early recurrence/metastasis related proteins of H-HCC after radical resection through multidimensional chromatography coupled with tandem mass spectrometry (2DLC-MS/MS). The different protein expression profiles between the early recurrence/metastasis within 6 months(R/M≤6months) and late recurrence/metastasis within 6-12 months after surgery (R/M6-12months) were confirmed and might reveal different underlying molecular mechanisms. We identified 44 and 49 significantly differentially expressed proteins in the R/M≤6months group and the R/M6-12months group compared to the group who had no recurrence within 2 years post surgery (the NR/M group), respectively. Moreover, among those proteins, S100A12 and AMACR were down regulated in the R/M≤6months group but up-regulated in the R/M6-12months group; and this regulation was further confirmed in mRNA and protein level by Q-PCR, Western-Blot and Immunohistochemistry (IHC).ConclusionsThis current study presents the first proteomic profile of the early recurrence/metastasis of H-HCC. The results suggest that S100A12 and AMACR might be potential prognostic markers for predicting the early recurrence/metastasis of H-HCC after hepatectomy.

| S-EPMC4023177 | biostudies-literature

Genetic Variants in the p14ARF/MDM2/TP53 Pathway Are Associated with the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated with Radical Resection.

Project description:The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/TP53 pathway and prognosis in ESCC patients with radical resection. 124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR = 2.77, 95% CI: 1.33-5.75, P = 0.006, Pc = 0.030) and disease-free survival (DFS) (HR = 2.45, 95% CI: 1.30-4.61, P = 0.005, Pc = 0.025). Moreover, patients with the DEL/A +AA genotype of MDM2 rs34886328 had a notably increased OS (HR = 0.27, 95% CI: 0.13-0.56, P = 4.7×10-4, Pc = 0.003) and DFS (HR = 0.22, 95% CI: 0.11-0.43, P = 1.1×10-5, Pc = 6.6×10-5). We also found that these two SNPs had a cumulative effect on the prognosis of ESCC, with the OS (P < 0.001) and DFS (P < 0.001) being shortest for patients carrying both of these unfavorable genotypes. In conclusion, genetic variants of the p14ARF/MDM2/TP53 pathway are significantly related to OS and DFS, and may be predictors of the prognosis of ESCC after surgery. We speculate the individuals with the TC/CC genotype of p14ARF rs3814960 and/or the DEL/DEL genotype of MDMD2 rs34886328 should have more aggressive treatment and may greatly benefit from early prediction and prevention of an unfavorable prognosis by genotyping before the initiation of therapy. These findings should be further validated in a larger population.

| S-EPMC4944974 | biostudies-literature

Long-term prognosis after endoscopic resection of T1a-MM/T1b-SM1 esophageal squamous cell carcinoma.

Project description:The objective of this study was to evaluate the long-term prognosis of T1a-MM/T1b-SM 1 esophageal squamous cell carcinoma (ESCC) after endoscopic resection (ER) and to validate the follow-up policy for pT1a-MM lymphovascular invasion (LVI)-negative ESCC. In this retrospective single-center analysis, patients who underwent ER for superficial ESCC between April 2002 and June 2021 were identified. The overall survival (OS), metastatic recurrence, and recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method. Cox proportional hazards models for OS, metastatic recurrence, and RFS were used. A total of 104 ESCC patients were eligible for the analysis. Of 104 patients, 81 had pT1a-MM, and 23 had pT1b-SM1. The 5-year OS, RFS, and metastatic recurrence rates of the 56 cases of pT1a-MM LVI-negative ESCC without additional treatment were 0.848 (95% confidence interval [CI]: 0.687-0.931), 0.817 (95% CI: 0.647-0.911), and 0.061 (95% CI: 0.014-0.240), respectively. Cox regression analysis for OS, RFS, and metastatic recurrence showed that only lymphatic invasion was strongly associated with metastatic recurrence (adjusted hazard ratio, 10.3; 95% CI: 2.01-53.3; P = .005). The proportion of deaths from other diseases was considerably higher (17/104, 16.3%) than that from ESCC (2/104, 1.9%). This may be related to the high complication rate of malignant tumors in other organs (43.3%, 45/104). The prognosis of ER for pT1a-MM and LVI-negative ESCC is good, and the follow-up policy is valid. Malignant tumors in other organs may be a major prognostic factor for superficial ESCC after ER.

| S-EPMC9750562 | biostudies-literature

Prognostic prediction and comparison of three staging programs for patients with advanced (T2-T4) esophageal squamous carcinoma after radical resection.

Project description:PurposeLymph node-based staging protocols are frequently employed to evaluate the prognosis of esophageal cancer, yet their accuracy remains contentious. The present study was conducted to assess the prognostic significance of three lymph node staging systems, namely N stage, lymph node rate (LNR), and log odds of positive lymph nodes (LODDS), in patients diagnosed with advanced (T2-T4) esophageal squamous cell carcinoma (ESCC).MethodsThis cohort comprised 319 eligible patients, with an additional 409 individuals retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, forming the validation cohort. Differences in overall survival (OS) of patients between groups were assessed using the log-rank test. Prognostic independent risk variables were identified, and lymph nodes (LN) prognostic models were built using multivariate Cox regression analysis. Besides, the predictive accuracy of each model was evaluated utilizing the (-2) log-likelihood ratio (-2LLR), the likelihood ratio χ2 score (LRχ2), the Akaike information criterion (AIC), and Harrell's concordance index (C-index). To further evaluate the potential superiority of the model, a nomogram was constructed for comparison with the conventional Tumor Node Metastasis (TNM) staging approach.ResultsIndependent prognostic factors for advanced ESCC include the N stage, LNR, and LODDS. Herein, LODDS presented higher values for C-index and LRχ2, and lower values for AIC and -2LLR in OS compared to the others. Consequently, a nomogram was constructed based on LODDS. Calibration curves exhibited strong agreement, and assessment through C-index, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA) demonstrated promising clinical applicability.ConclusionLODDS emerges as a promising future prognostic indicator. After surgery, the proposed model holds the potential to provide valuable treatment recommendations for patients with advanced ESCC.

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Prognostic Impact of Pretreatment Serum CYFRA Status in 1047 Patients with Esophageal Squamous Cell Carcinoma Who Underwent Radical Resection: A Japan Esophageal Society Promotion Research.

Project description:PurposeThe prognostic significance of pretreatment serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) status was evaluated in the patients with surgically treated esophageal squamous cell carcinoma.MethodsA total of 1047 patients with surgically treated esophageal cancer were enrolled in a multi-institutional study promoted by the Japanese Esophageal Society. This study included an up-front surgery group (n = 412), a neoadjuvant chemotherapy (NAC) group (n = 486), and a neoadjuvant chemoradiation/radiation therapy (NACRT/RT) group (n = 149). The pretreatment CYFRA status was analyzed to assess prognostic significance using multivariate analysis according to treatment modalities.ResultsThe CYFRA-positive group was significantly associated with deep tumor. Univariate analysis showed that the overall survival of the CYFRA-positive group was significantly worse than that of the CYFRA-negative group, but the difference was not significant in the multivariate analysis. CYFRA was an independent risk factor for poor prognosis just in the NACRT/RT group.ConclusionsThe CYFRA-positive group was associated with deep tumor and poor survival. Pretreatment CYFRA was not an independent risk factor for poor prognosis in the up-front surgery group or NAC group. It was an independent risk factor for poor prognosis just in the NACRT/RT group.

| S-EPMC9209890 | biostudies-literature

Genetic polymorphisms of ATG5 predict survival and recurrence in patients with early-stage esophageal squamous cell carcinoma.

Project description:Esophageal squamous cell carcinoma (ESCC) is a deadly disease with high risk of tumor recurrence even among patients with an early pathologic stage of tumor. In the current study, we investigate the association between 20 SNPs of the ATG5 gene and prognosis of patients with early-stage ESCC. A total of 305 patients diagnosed with early-stage ESCC were enrolled in the study and randomly assigned to a training set (n=93) or replication set (n=212). The genotypes of candidate SNPs (single nucleotide polymorphisms) within ATG5 were analyzed and correlated with the prognosis of ESCC patients. We repeatedly demonstrated that 3 SNPs in ATG5, rs1322178, rs3804329, and rs671116, were significantly correlated with the prognosis of patients with early-stage ESCC (HR[95 % CI]=2.01[1.19-3.40], p=0.009 for ATG5: rs1322178; HR[95 % CI]=1.88 [1.08-3.26], p=0.025 for ATG5:rs3804329; HR[95 % CI]=1.73[1.24-2.42], p=0.001 for ATG5:rs671116, in combined group). Both rs1322178 and rs3804329 can predict early distant metastasis of patients. Furthermore, increased expression of ATG5 was observed in ESCC tumor tissue as compared to adjacent normal tissue. Moreover, higher levels of ATG5 expression in both normal and tumor tissues exhibited a trend to correlate with poor prognosis of patients. However, the expression of ATG5 did not correlate with these 3 relevant prognostic SNPs. We concluded that hereditary genetic polymorphisms and gene expression of ATG5 can serve as prognostic predictors of patients with early-stage ESCC.

| S-EPMC5710940 | biostudies-literature

A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.MethodsWe developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).ResultsThe expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.ConclusionsThis technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

| S-EPMC4143329 | biostudies-literature

UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma.

Project description:Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC). Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA-ESCC cohort. Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and high-risk groups with significantly different overall survival in the TCGA-ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group. Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.

| S-EPMC8262217 | biostudies-literature

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