Protein predictive signatures for lymph node metastasis of gastric cancer

Abstract

Lymph node status remains one of most crucial indicators of gastric cancer prognosis and treatment planning. Current imaging methods have limited accuracy in predicting lymph node metastasis. We sought to identify protein markers in primary gastric cancer and to define a risk model to predict lymph node metastasis. The Protein Pathway Array (PPA) (initial selection) and Western blot (confirmation) were used to assess the protein expression in a total of 190 freshly frozen gastric cancer samples. The protein expression levels were compared between samples with lymph node metastasis (n 5 73) and those without lymph node metastasis (n 5 57) using PPA. There were 27 proteins differentially expressed between lymph node positive samples and lymph node negative samples. Five proteins (Factor XIII B, TFIIH p89, ADAM8, COX-2 and CUL-1) were identified as independent predictors of lymph node metastasis. Together with vascular/lymphatic invasion status, a risk score model was established to determine the risk of lymph node metastasis for each individual gastric cancer patient. The ability of this model to predict lymph node metastasis was further confirmed in a second cohort of gastric cancer patients (33 with and 27 without lymph node metastasis) using Western blot. This study indicated that some proteins differentially expressed in gastric cancer can be selected as clinically useful biomarkers. The risk score model is useful for determining patients' risk of lymph node metastasis and prognosis.Gastric cancer is the fourth most common malignancy and the second leading cause of cancer-related death, after lung cancer, in the world. More than 80% of patients are diagnosed at an advanced stage or experienced tumor recurrence after surgical resection.1 Despite of some decline in the incidence and prolonged overall survival of gastric cancer patients in the past decade thanks to the advancement of treatments (e.g., surgery, chemotherapy and radiotherapy), gastric cancer continues to be a major health problem with a high mortality rate. 2Most gastric cancer patients are diagnosed at Stages III or IV, with 50-75% of patients presenting with lymph node metastasis.3 The preoperative determination of lymph node status is critical in tumor staging and in planning optimal management of gastric cancer patients. For early gastric cancer without lymph node involvement, less invasive treatment (e.g., endoscopic mucosal resection) can be performed. For localized gastric cancer without lymph node involvement, surgical resection with limited lymph node dissection is recommended to reduce postoperative morbidity and mortality. For advanced gastric cancer with lymph node involvement, surgical resection with extensive lymphadenectomy is necessary to achieve better outcome. 4 Currently, preoperative assessment of lymph node status is mainly based on imaging studies such as computerized tomography, magnetic resonance imaging and positron emission tomography/computed tomography. However, many studies show that lymph node size determined by imagin...

Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer

“…Although previous studies reported that ADAM8 expression correlates significantly with tumor size, histological differentiation, regional and distant metastasis, tumor stages in several cancers progression [12, 13, 29, 31], we did not find any significant correlations between ADAM8 expression status and any clinicopathological feature in CRC.…”

Upregulation of a disintegrin and metalloprotease 8 is associated with progression and prognosis of patients with gastric cancer

“…In this study, ADAM8 protein expression in the tumor tissues was significantly correlated with invasion depth (pT stage), lymph node involvement (pN stage), and vessel invasion, which is in agreement with recent published studies of gastric and prostate cancer. 12,26 Furthermore, no correlation was found with TNM stage, although a previous study has revealed differing results. 25 Survival analysis demonstrated that patients with positive ADAM8 expression have shorter survival times than those with negative expression and that this protein is an independent predictor of poor survival of GC patients, which is consistent with the results of studies on lung, renal, and brain cancers.…”

“…[6][7][8][9] Of them, members of a disintegrin and metalloproteinases (ADAMs) family are involved in invasion and metastasis in GC. [10][11][12] ADAM8, a member of the ADAMs family, was initially reported to play potential roles in inflammatory and allergic processes, 13 and further studies have shown that its overexpression is associated with progression and poor survival in various solid tumors. 12,14,15 ADAM8 has been reported to be an independent indicator of lymph node metastasis in human GC 12 ; however, its precise effects on GC progression and prognosis remain unclear.…”

“…[10][11][12] ADAM8, a member of the ADAMs family, was initially reported to play potential roles in inflammatory and allergic processes, 13 and further studies have shown that its overexpression is associated with progression and poor survival in various solid tumors. 12,14,15 ADAM8 has been reported to be an independent indicator of lymph node metastasis in human GC 12 ; however, its precise effects on GC progression and prognosis remain unclear. In this study, we focused on the correlation of ADAM8 expression with clinicopathologic features and overall survival (OS); in addition, the mechanisms implicating this protein in GC progression were studied at the molecular level by in vitro assays.…”

Profiling of serum metabolites in advanced colon cancer using liquid chromatography‑mass spectrometry

“…Furthermore, hierarchical clustering analysis was conducted using BRB-Array Tools version 3.6 software (developed by Dr Richard Simo & BRB-Array Tools Development Team) to distinguish patients with stage T3 colon cancer with and without lymph node metastasis. The global median subtraction method (26,27) was used to normalize the intensity of the background interference. In addition, the clinicopathological characteristics of the patients were collected, including sex, age, tumor size, presence of invasion to the blood or lymph vessels, p53 expression, Ki-67 serum level, history of alcohol consumption, tobacco smoking and family tumor history, analyzed using a χ 2 test or Fisher's exact test.…”