Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification

Abstract

Wei-Juan Zeng,1 Chun-Wei Peng,1 Jing-Ping Yuan,1 Ran Cui,2 Yan Li11Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, People’s Republic of China; 2Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education) and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, People’s Republic of China Purpose: The aims of this study are to establish a new method for simultaneously detecting the interactions between cancer cells and immunocytes in malignant ascites (MA) and to propose a new model for MA classification.Methods: A quantum dot (QD)-based multiplexed imaging technique was developed for simultaneous in situ imaging of cancer cells, lymphocytes, and macrophages. This method was first validated in gastric cancer tissues, and then was applied to MA samples from 20 patients with peritoneal carcinomatosis from gastrointestinal and gynecological origins. The staining features of MA and the interactions between cancer cells and immunocytes in the ascites were further analyzed and correlated with clinical features.Results: The QD-based multiplexed imaging technique was able to simultaneously show gastric cancer cells, infiltrating macrophages, and lymphocytes in tumor tissue, and the technique revealed the distinctive features of the cancer tumor microenvironment. When this multiplexed imaging protocol was applied to MA cytology, different features of the interactions and quantitative relations between cancer cells and immunocytes were observed. On the basis of these features, MA could be classified into immunocyte-dominant type, immunocyte-reactive type, cancer cell-dominant type, and cell deletion type; the four categories were statistically different in terms of the ratio of cancer cells to immunocytes (P<0.001). Moreover, in the MA, the ratio of cancer cells to immunocytes was higher for patients with gynecological and gastric cancers than for those with colorectal cancer.Conclusion: The newly developed QD-based multiplexed imaging technique was able to better reveal the interactions between cancer cells and immunocytes. This advancement allows for better MA classification and, thereby, allows for treatment decisions to be more individualized. Keywords: gastric cancer, malignant ascites, quantum dots, classification, multiplexed imaging