ADC correlation with Sirtuin1 to assess early chemoradiotherapy response of locally advanced esophageal carcinoma patients

Ying Chen,Jun Fang,Qingren Lin,Tieming Xie,Zhimin Ye,Zhun Wang,Kai Li,Zhenfu Fu,Dan Long,Mingxiang Jiang,Fangzheng Wang

doi:10.1186/s13014-019-1393-y

Abstract

AimsTo determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT).MethodsA total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1~2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and ΔADC, ADCratio were calculated. Pearson’s correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman’s rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT.ResultsThe findings of this study showed different correlations between ADC values and the levels of SIRT1 (ΔADC: r = − 0.943, P = 0.002; ADCratio: r = − 0.911, P = 0.000; intra-ADC: r = − 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between ΔADC and early response to treatment (ρ = 0.615, P = 0.023), and multivariable logistic regression revealed that ΔADC was significantly associated with short-term response of CRT in esophageal carcinoma patients.ConclusionsIn summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.

Highlights

Esophageal carcinoma (EC) is one of the most devastating cancer worldwide, including over 450,000 new cancer diagnoses yearly, and in some areas of China, this disease is the fourth leading cause of mortality from cancer, with an esophageal squamous cell carcinoma (ESCC) histology in approximately > 90% of cases [1, 2]
In our previous study [15], we found that the expression level of protein Sirtuin-1 (SIRT1) was higher in CRT nonresponder patients with ESCC than in CRT responder patients, and suppression of SIRT1 may inhibit the growth of ESCC cell lines
We demonstrated that the downregulation of SIRT1 expression may inhibit the growth of ESCC cell lines, and that SIRT1 may be a biomarker for the treatment of EC [16]

Summary

Introduction

Esophageal carcinoma (EC) is one of the most devastating cancer worldwide, including over 450,000 new cancer diagnoses yearly, and in some areas of China, this disease is the fourth leading cause of mortality from cancer, with an esophageal squamous cell carcinoma (ESCC) histology in approximately > 90% of cases [1, 2]. Most patients diagnosed with esophageal cancer are at a locally advanced stage with unresectable or metastatic disease; concurrent chemo-radiotherapy (CRT) is currently considered the best treatment modality [3]. Patients who are insensitive to CRT (18–25%) may be damaged by the toxicity of an ineffective therapy without survival benefit [4]. A phase III clinical trial documented that the survival or local/regional control in the group with a higher radiation dose (64.8 Gy) was not increased compared to that in the group with the lower radiotherapy dose (50.4 Gy) [5]. In the CROSS phase III trial, disease-free survival (DFS) and overall survival were improved in the group that underwent preoperative chemoradiotherapy (CRT) compared with the group that underwent surgery alone [6]

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Conclusion