Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non–small cell lung cancer after concurrent chemoradiation
Authors: Xi Liu
Steven H Lin
Kenneth Hess
Ting Xu
Li Liu
Yang Liu
Jia Fan
Zhongxing Liao
Navid Ahmadinejad
Tony Y Hu
Bo Ning
Jianjun Zhang
Journal: Science Advances (2020)
Discipline: Multidisciplinary
Keywords: Non-small cell lung cancer; NSCLC; extracellular vesicles; EVs; proteomics
Affiliations: Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA., Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Molecular Pharmacology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Abstract:  Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. More than half of patients with NSCLC die after developing distant metastases, so rapid, minimally invasive prognostic biomarkers are needed to reduce mortality. We used proteomics to identify proteins differentially expressed on extracellular vesicles (EVs) of nonmetastatic 393P and metastatic 344SQ NSCLC cell lines and found that tetraspanin-8 (Tspan8) was selectively enriched on 344SQ EVs. NSCLC cell lines treated with EVs overexpressing Tspan8 also exhibited increased Matrigel invasion. Elevated Tspan8 expression on serum EVs of individuals with stage III premetastatic NSCLC tumors was also associated with reduced distant metastasis-free survival, suggesting that Tspan8 levels on serum EVs may predict future metastasis. This result suggests that a minimally invasive blood test to analyze EV expression of Tspan8 may be of potential value to guide therapeutic decisions for patients with NSCLC and merits further study. 

Retracted: No

PubPeer comments:
 ![file] In figure 2, the quantified intensity does not match the WB result , 
 #1 We thank Sarcophaga Nearctica for the interest in our study, and regret that we did not notice this post earlier. The heatmap referred to was generated using image intensity data obtained using Image J to measure the mean intensity of the pixels within a rectangular region defined for each gene that represented the minimal area required to cover the band or bands of interest. The bands and heat maps indicated differed as a result of the number of bands analyzed in these samples. We analyzed both intact and cleaved Filamin-A in this analysis, so that the heat map for Filamin-A included both a high intensity band, similar to that observed for Clusterin, as well as the weaker band and intervening area between these two bands. This additional area of reduced signal was responsible for the specific heat map differences between these two proteins. This difference was also emphasized by the saturation point of the heat map color range, which was set at 80 in order to emphasize the differences among the non-saturated bands, which would provide more reliable indications of expression differences. This choice, however, eliminated differences between highly expressed genes rendering them indistinguishable on this heat map. Neither Clusterin nor Filamin-A were pursued in this study, since Filamin-A did not markedly differ among the EVs of the two cell lines, while the expression of Clusterin was also high in EV-depleted culture media indicating that its release was not restricted to EV secretion. ,