Proteomic profiling of plasma exosomes reveals CD82 involvement in the development of esophageal squamous cell carcinoma

The Xinjiang Uygur autonomous region has a high incidence of esophageal cancer. For the early diagnosis of patients with esophageal squamous cell carcinoma (ESCC), exosomes were isolated and quantified by liquid chromatography tandem mass spectrometry ((LC-MS/MS) with data independent acquisition (DIA) from the peripheral blood of patients with benign esophageal disease (BED), esophageal intraepithelial neoplasia (EIN) and ESCC. A total of 1117 proteins were identified in the above 9 samples. The proteomic results showed that the quantity of CD82 in exosomes of EIN was significantly higher than that in patients with BED and ESCC. Meanwhile, our ELISA test verified our proteomic results. In addition, the immunohistochemical results showed high CD82 expression in adjacent normal tissues and low expression in ESCC tissues. CD82 expression in ESCC tissues was negatively correlated with tumor stage and the expression of PKM2, and the high expression of CD82 combined with low expression of PKM2 in ESCC tissues suggested a good prognosis. To further clarify the tumor suppressive mechanism of CD82, the TIMER and TISDB databases were analyzed, and CD82 expression in tumor tissues was found to be related to the infiltration of immune cells. CD82 in exosomes is involved in the development of ESCC. SIGNIFICANCE: Xinjiang is a high incidence area of ESCC. When diagnosed in the middle and late stages of the disease, the prognosis of patients is poor. Exosomes provide the possibility of relatively noninvasive and early detection of esophageal carcinogenesis. To the best of our knowledge, this was the first study using the DIA technique to analyze the exosomal proteins of patients with different stages of ESCC. The proteins identified in the exosomes in these three groups could provide insights for understanding how exosomes promote the occurrence of ESCC, the antitumour mechanism of humans and the early diagnosis of ESCC.