Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer.

Abstract

Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen-IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan-Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast, and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric, and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast, and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells.

• Authors: Alessandro Mangogna, Beatrice Belmonte, Chiara Agostinis, Giuseppe Ricci, Alessandro Gulino, Ines Ferrara, Fabrizio Zanconati, Claudio Tripodo, Federico Romano, Uday Kishore, Roberta Bulla
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 1748 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30127783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Pulmonary Surfactant-Associated Protein D
• RNA, Neoplasm

Topics

• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (genetics, metabolism)
• Computational Biology
• Computer Simulation
• Datasets as Topic
• Female
• Humans
• Lung Neoplasms (genetics, metabolism)
• Male
• Neoplasms (metabolism)
• Ovarian Neoplasms (genetics, metabolism)
• Prognosis
• Pulmonary Surfactant-Associated Protein D (genetics, metabolism)
• RNA, Neoplasm
• Stomach Neoplasms (genetics, metabolism)
• Survival Analysis