Usefulness of serum protein profiling for prediction of preoperative chemoradiosensitivity of esophageal cancer

Abstract

Abstract. We examined whether serum protein profiling is a reliable index for prediction of therapeutic efficacy of preoperative chemoradiotherapy (PCRT) in advanced esophageal cancer compared with evaluation of the efficacy of conventional clinical examination. We entered 42 patients who received PCRT and surgery between 1998 and 2002 into this study. Serum protein profiling was performed using the preoperative serum of the patient to select the marker set that enabled the efficacy of PCRT to be evaluated accurately. The efficacy of PCRT was predicted with the marker set, and the sensitivity, specificity and accuracy of the method were calculated based on evaluation of the efficacy by pathological examination. Similarly, therapeutic efficacy was also predicted based on evaluation of the efficacy of conventional clinical examination, and the results were compared with those of prediction by serum protein profiling. The correlation between each predictive examination and outcome was evaluated. The sensitivity, specificity and accuracy of prediction of therapeutic efficacy of PCRT by serum protein profiling were 90.9, 100 and 93.3%, respectively. In clinical examination, prediction of the efficacy of PCRT by three methods was as follows: by esophagography, sensitivity 76.0%, specificity 17.6%, accuracy 52.4%; by endoscopy, sensitivity 80.0%, specificity 11.8%, accuracy 52.4%; by computed tomography, sensitivity 60.0%, specificity 47.1%, accuracy 54.8%, respectively. These results demonstrated the superiority of serum protein profiling in predicting the therapeutic efficacy of PCRT compared with conventional clinical examination. Moreover, serum protein profiling was the only significant prognostic factor as regards the correlation with outcome by multivariate analysis. IntroductionEsophageal cancer generally has a poor prognosis and cannot be cured by surgery alone because it readily develops lymph node metastasis or invades into the trachea, bronchi or large vessels, especially if advanced. Since esophageal cancer is sensitive to chemotherapy and radiotherapy, various approaches to multidisciplinary treatment in which chemoradiotherapy is combined with surgical treatment have been made. Among them, preoperative chemoradiotherapy (PCRT), which came into use in the 1980s in Europe and North America, is reported to enhance the treatment results of advanced esophageal cancer by improving resection rates evaluating local control or by inhibiting post-operative recurrence by controlling minute metastatic lesions (1-3). However, several studies have revealed that PCRT does not affect all patients with esophageal cancer but improves the survival rates only when it is pathologically effective (4,5). In ineffective cases, PCRT is actually disadvantageous due to its side effects. It is therefore important to properly predict the therapeutic efficacy of PCRT and to use PCRT only for those cases in which effect can be anticipated. In order to discover a new diagnostic that can accurately predict the efficacy of PCRT, we perfo...

Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer

“…A similar study performed by SELDI-TOF MS in patients with oesophageal squamous cell carcinomas proposed four unidentified serum markers ( m / z 7420, 9112, 17 123 and 12 867) associated with chemoradiotherapy response in 14 out of 15 patients ( Hayashida et al , 2005 ) as the only significant association with outcome by multivariate analysis ( Ota et al , 2007 ). The current study, performed with plasma samples predominantly in patients with adenocarcinomas, did not confirm this previously reported serum panel.…”

“…One study using SELDI-TOF MS reported four peaks of undisclosed identity that differentiated between responders and non-responders in 14 patients treated with chemoradiotherapy for oesophageal squamous cell carcinoma ( Hayashida et al , 2005 ) and were superior to radiological and pathological techniques in assessing response to therapy ( Ota et al , 2007 ), but no comparable studies have been performed on the now more common adenocarcinoma of the oesophagus.…”

Detection of oesophageal cancer biomarkers by plasma proteomic profiling of human cell line xenografts in response to chemotherapy

“…Surface-enhanced laser desorption/ionisation time-of-flight MS has been reported to differentiate between responders and non-responders treated with chemoradiotherapy ( Hayashida et al , 2005 ; Ota et al , 2007 ). In a single study of chemo-radiotherapy in patients with squamous cell carcinoma of the oesophagus, a panel of four peaks was identified, which distinguished chemo-radiotherapy response in 14 out of 15 patients.…”

“…In a single study of chemo-radiotherapy in patients with squamous cell carcinoma of the oesophagus, a panel of four peaks was identified, which distinguished chemo-radiotherapy response in 14 out of 15 patients. Although the identity of these markers was not reported ( Hayashida et al , 2005 ), the performance of this four-peak panel was superior to radiological and pathological techniques in assessing response to therapy ( Ota et al , 2007 ).…”

Proposal of a Punch Biopsy Protocol as a Pre-requisite for the Establishment of a Tissue Bank from Resected Esophageal Tumors

“…This has in turn increased the demand for high-quality tissue and biological samples. Genomic and proteomic research in the field of esophageal carcinoma is quickly growing with the aim to identify the predictors for response to chemoradiation therapy [7,8]. In recent years, many biological tissue banks have been established.…”