Abstract

With the rapid advances of low-dose computed tomography (LDCT) screening for lung cancer, the opportunity to detect subcentimeter non-small cell lung cancer (NSCLC) is gradually increasing. The results of many previous studies have shown that even subcentimeter NSCLCs are not always in the early stage. Thus, it is quite important for us to judge the possibility of malignancy for these patients, even the tumor size is less than 10mm. However, subcentimeter lung cancer is hard to diagnose only via biopsy and imaging features because of its tinny size. Chronic inflammation is well established as a hallmark in lung carcinogenesis. In our previous study, B lymphocyte chemoattractant (BLC), is found to be slightly associated with the risk of subcentimeter lung adenocarcinoma. The aim of the present study is to evaluate the correlation between TNF receptor type II (TNFRII) and the risk for subcentimeter lung adenocarcinoma, and the efficacy of diagnosing subcentimeter lung cancer after combining TNFRII and BLC. Inflammatory biomarkers were measured in 71 subcentimeter lung adenocarcinoma patients and 71 age-, sex- and smoking-matched healthy controls by using the Luminex bead-based assay. The mean (standard deviation or SD) age of patients was 56.01 (8.91) years, and 73.20% of them were female patients (n=52). Never smokers accounted for 85.96% of patients (n=57). The expression level of TNFRII is significantly down-regulated in subcentimeter lung adenocarcinoma patients compared with the healthy controls (P<0.001). And the results were validated by oncomine data mining analysis. Elevated levels of TNFRII were associated with an 89% reduced risk for subcentimeter lung adenocarcinoma. (OR=0.11, 95% CI: 0.04-0.30, P=2.4*10-5). BLC was associated with a 2.70-fold (95% CI: 1.31-5.58, P=7.0*10-3) increased risk of subcentimeter lung adenocarcinoma for the comparison of patients in the higher-level group with the lower-level group. To yield more information, the BLC/TNFRII ratio was created to examine their prediction for the risk of subcentimeter lung adenocarcinoma, and as expected there was a 35- fold increased risk for patients in the higher-level group relative to patients in the lower-level group. Further ROC curve analysis revealed that TNFRII was a significant diagnostic biomarker for subcentimeter lung adenocarcinoma, with the area under the curve of 0.73 (95% CI: 0.65-0.82, P=2.0*10-6). The sensitivity, specificity and accuracy were 0.75, 0.72 and 0.73, respectively. Our findings demonstrated that TNFRII was associated with the significant risk of subcentimeter lung adenocarcinoma, and could be a promising biomarker for accessorily diagnosing subcentimeter lung adenocarcinoma.

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