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Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

ABSTRACT: Here, we aimed to identify an immunohistochemical (IHC)-based classifier as a prognostic factor in patients with esophageal squamous cell carcinoma (ESCC). A cohort of 235 patients with ESCC undergoing radical esophagectomy (with complete clinical and pathological information) were enrolled in the study. Using the least absolute shrinkage and selection operator (LASSO) regression model, we extracted six IHC features associated with progression-free survival (PFS) and then built a classifier in the discovery cohort (n = 141). The prognostic value of this classifier was further confirmed in the validation cohort (n = 94). Additionally, we developed a nomogram integrating the IHC-based classifier to predict the PFS. We used the IHC-based classifier to stratify patients into high- and low-risk groups. In the discovery cohort, 5-year PFS was 22.4% (95% CI: 0.14-0.36) for the high-risk group and 43.3% (95% CI: 0.32-0.58) for the low-risk group (P = 0.00064), and in the validation cohort, 5-year PFS was 20.58% (95% CI: 0.12-0.36) for the high-risk group and 36.43% (95% CI: 0.22-0.60) for the low-risk group (P = 0.0082). Multivariable analysis demonstrated that the IHC-based classifier was an independent prognostic factor for predicting PFS of patients with ESCC. We further developed a nomogram integrating the IHC-based classifier and clinicopathological risk factors (gender, American Joint Committee on Cancer staging, and vascular invasion status) to predict the 3- and 5-year PFS. The performance of the nomogram was evaluated and proved to be clinically useful. Our 6-IHC marker-based classifier is a reliable prognostic tool to facilitate the individual management of patients with ESCC after radical esophagectomy.

SUBMITTER: Meng J

PROVIDER: S-EPMC5792740 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

Meng Jin J Zhang Junhua J Xiu Yingjie Y Jin Yan Y Xiang Jiaqing J Nie Yongzhan Y Fu Shen S Zhao Kuaile K

Molecular oncology 20180106 2

Here, we aimed to identify an immunohistochemical (IHC)-based classifier as a prognostic factor in patients with esophageal squamous cell carcinoma (ESCC). A cohort of 235 patients with ESCC undergoing radical esophagectomy (with complete clinical and pathological information) were enrolled in the study. Using the least absolute shrinkage and selection operator (LASSO) regression model, we extracted six IHC features associated with progression-free survival (PFS) and then built a classifier in t ...[more]

PMID: 29160958

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Project description:BackgroundChronic inflammation is deemed to play a significant effect on initiation and progression of esophageal squamous cell carcinoma (ESCC). In current study, we investigated the prognostic and predictive role of albumin (Alb) to fibrinogen (Fib) ratio (AFR) and a novel AFR-Alb-derived neutrophil/lymphocyte ratio (dNLR) score (ADS) in ESCC patients undergoing esophagectomy and compared them with Fib, Alb, neutrophil to lymphocyte ratio (NLR), dNLR, platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR).Materials and methodsA total of 153 clinical confirmed ESCC patients undergoing esophagectomy between January 2011 and December 2013 were included in present study. We detected preoperative Alb, Fib and neutrophil, monocyte, lymphocyte and platelet count, and obtained overall survival (OS) by 3 years' follow-up in the cases. X-tile software, Kaplan-Meier curve, Cox regression and predicted nomogram were used to evaluate the predictive and prognostic role of them in ESCC patients.ResultsThe optimal cut-off values of Fib, Alb, AFR, NLR, dNLR, PLR and LMR were 3.2 mg/dL, 38.2 g/L, 9.3, 2.1, 4.3, 145.9 and 2.3, respectively. High levels of Fib [(adjusted hazard ratio (HR) = 2.148, 95% confidential interval (CI) (1.229-3.753)], dNLR (adjusted HR = 2.338, 95% CI 1.626-5.308) and PLR (adjusted HR = 1.964, 95% CI 1.129-3.415) as well as low AFR (adjusted HR = 2.381, 95% CI 1.152-4.926) and Alb (adjusted HR = 2.398, 95% CI 1.342-4.273) were significantly associated with decreased OS in ESCC patients. The survival predictive areas under the time-dependent receiver operating characteristics curve of AFR, dNLR and Alb were higher than Fib and PLR, respectively. High ADS score was significantly associated with short 3 years' OS of ESCC patients (adjusted HR = 2.94, 95% CI 1.70-5.08). Moreover, OS of ESCC patients receiving adjuvant radio-chemotherapy was longer than those without the treatment in high ADS score subgroup (p = 0.001), however, no significant survival difference was observed in the patients with or without treatment radio-chemotherapy (p = 0.297). Additionally, a significant difference was observed in c-index values of the nomograms including or without ADS (0.720 vs. 0.670, p < 0.05).ConclusionsPreoperative ADS was a prospective biomarker to predict clinical efficacy of adjuvant radio-chemotherapy and clinical prognosis of ESCC patients undergoing esophagectomy, and the score could apparently improve predicted efficacy of the nomogram.

Project description:PurposeThough postoperative radiation for esophageal squamous cell carcinoma is offered in selected cases, there is conflicting evidence as to whether it improves overall survival (OS). A retrospective investigation was performed to analyze the prognostic impact of postoperative radiation therapy (PORT) in a large cohort of patients.MethodsFrom 2001 to 2009, 725 patients underwent radical esophagectomy (R0) with or without PORT were eligible for retrospective analysis. Patients were grouped into surgery alone (n = 467) and surgery plus PORT (n = 258). Median irradiation doses were 50 Gy (range: 40-56 Gy). Radiation fields encompassed the bilateral supraclavicular fossa, mediastinum, subcarinal area, and the tumor bed for the upper/middle-third disease; the bilateral supraclavicular fossa, mediastinum, the tumor bed, subcarinal area, and lower thoracic paraesophageal area for the lower-third disease. Kaplan-Meier and Cox regression analysis were used to compare OS.ResultsAfter median follow-up of 53 months, the median OS was 29 months in the PORT group and 23 months in the surgery alone group. The addition of PORT improved OS at 3 years from 36.6 to 43.6% compared with surgery alone. The use of PORT was associated with significantly improved OS (p = 0.018). For American Joint Committee on Cancer (AJCC) stage III esophageal cancer (T1-2N2M0, T3N1-2M0, T4N1-3M0), there was significant improvement in OS (p = 0.002) in the PORT group, not only for lymph-node metastatic ratio (LNMR) ≥0.25 (p = 0.001), but also for LNMR <0.25 (p = 0.043). However, for stage IIB disease (T1-2N1M0) there was no significant differences. The addition of POCT didn't prolong the OS significantly (Surgery alone group, p = 0.079; PORT group, p = 0.111).ConclusionsThis large retrospective analysis supports the use of PORT for pathologic lymph node positive stage III esophageal squamous cell carcinoma. Given the retrospective nature of this study, the results should be confirmed by appropriately powered randomized trials. Further development of adjuvant therapy in EC is warranted.

Dataset Information

Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

Publications

Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

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