Background Although uveal melanoma (UM) at the early stage is controllable to some extent, it inevitably ultimately leads to death due to its metastasis. At present, the difficulty is that there is no way to effectively tackle the metastasis. It is hypothesized that these will be treated by target molecules, but the recognized target molecule has not yet been found. In this study, the target molecule was explored through proteomics. Methods Transgenic enhanced green fluorescent protein (EGFP) inbred nude mice, which spontaneously display a tumor microenvironment (TME), were used as model animal carriers. The UM cell line 92.1 was inoculated into the brain ventricle stimulating metastatic growth of UM, and a graft re-cultured Next, the UM cell line 92.1-A was obtained through monoclonal amplification, and a differential proteomics database, between 92.1 and ectopic 92.1-A, was established. Finally, bioinformatics methodologies were adopted to optimize key regulatory proteins, and in vivo and in vitro functional verification and targeted drug screening were performed. Results Cells and tissues displaying green fluorescence in animal models were determined as TME characteristics provided by hosts. The data of various biological phenotypes detected proved that 92.1-A were more malignant than 92.1. Besides this malignancy, the key protein p62 (SQSTM1), selected from 5267 quantifiable differential proteomics databases, was a multifunctional autophagy linker protein, and its expression could be suppressed by chloroquine and dacarbazine. Inhibition of p62 could reduce the malignancy degree of 92.1-A. Conclusions As the carriers of human UM orthotopic and ectopic xenotransplantation, transgenic EGFP inbred nude mice clearly display the characteristics of TME. In addition, the p62 protein optimized by the proteomics is the key protein that increases the malignancy of 92.1 cells, which therefore provides a basis for further exploration of target molecule therapy for refractory metastatic UM.

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Background: The links between brain metastases of lung cancer and human cytomegalovirus (HCMV) infection have been controversial for a long time. This study aims to explore the links between brain metastases of lung cancer and HCMV infection from the perspective of expression and detection of HCMV immediate early gene (IE), guanine nucleotide-binding protein 4 (GBP4), CXC chemokine receptor 4 (CXCR4), thyroid transcription factor 1 (TTF1) and epidermal growth factor receptor (EGFR) proteins. Methods: We collected brain metastases specimens and lung primary tumor specimens of a series of patients that have not undergone any treatment. Conventional hematoxylin and eosin staining and immunohistochemical staining of target molecules was performed. We used the ImageJ software to process the average optical density value of immune complexes and GraphPad Prism 8.0.1 to perform image analysis, and the SPSS 22.0 statistics package (t test) to analyze the expression differences of target molecules.Results: Based on five cases of brain metastases and two cases of lung primary tumors, a total of seven samples were investigated. Conventional pathology diagnosis reported four cases of brain metastases of lung adenocarcinoma and one case of brain metastases of mixed small cell lung cancer with adenocarcinoma. Among the 19 molecular immunopathological test samples, only GBP4, related to HCMV infection, and TTF1, related to metastases, were highly expressed in all seven samples. A comparison of the AOD values of the primary lung cancer to the AOD values of brain metastases, yielded statistically significant differences as follows: in Case No.1, GBP4 (p=0.016), EGRF (p<0.001); in Case No. 2, IE (p<0.001), CXCR4 (p=0.005), EGFR (p=0.023), TTF1 (p=0.004). Conclusions: Although TTF1 is known to be a kinesin for brain metastases of lung cancer cells and it is associated with poor survival prognosis, the role of GBP4, which is closely related to HCMV infection and a key protein of brain metastases of lung cancer, remains unknown. The findings provide new knowledge into the role of GBP4 and could provide clues for devising novel strategies for target molecular therapy research in brain metastases of lung cancer in the context of HCMV infection.