Exosomal Tmem88 Protein As A Potential Biomarker In Liquid Biopsy For Non-Small-Cell Lung Cancer

BACKGROUND: The occurrence, development and prognosis of tumors are positively correlated to the expression levels of TMEM88 protein. This study was to investigate the potential of using TMEM88 protein levels in serum-derived exosomes as a biomarker for diagnosis in liquid biopsy of non-small cell lung cancer (NSCLC).METHODS: Specimen was obtained from 22 patients with primary NSCLC prior to treatment (untreated group) and 10 patients after surgical resection (surgical group). An additional 10 patients with benign (benign group). as well as 10 age-and gender-matched controls (control group) were also included. Exosomes were isolated from serum of subjects using ultracentrifiigation and identified by transmission electron microscope and western blot of exosome markers TSG101 and CD63. The expression of TMEM88 protein was quantified by western blot and immunohistochemistry in exosomes and tumor tissue respectively.RESULTS: The expression levels of exosomal TMEM88 protein was significantly higher in the un-treated group compared to the surgical, benign and control groups (P<0.001), while no statistically significant differences were seen between the surgical and benign or control group. In the un-treated group, the expression levels of exosomal TMEM88 were positively correlated with increased tumor stage, and were also significantly higher in patients with lymph node metastasis or vascular tumor emboli than those without. Significant correlation between the expression levels of exosomal TMEM88 and TMEM88 in the tumor tissue was shown in the un-treated groups using the Pearson rank correlation test (r=0.637, P=0.048).CONCLUSIONS: TMEM88 was over-expressed in the serum-derived exosomes from NSCLC patients and the levels are consistent with that found in tumor tissue. Increased TMEM88 expression was associated with increased tumor burden, pathological stage, lymph node metastasis and vascular tumor emboli.