Mucins as Potential Biomarkers for Early Detection of Cancer

Abstract

Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients' sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.

Keywords: autoantibodies; early cancer detection; exosomes; liquid biopsies; mucin biomarker.

Figure 1

Mucin expression profile in human malignancies. Mucins are highly deregulated proteins in major human cancers. The right panel in the figure shows changes in the mucin profile in lung cancer, liver cancer, colon cancer, and prostate cancer, whereas the left panel shows mucin deregulation in breast, pancreas, and ovary cancers. A comparison of mucin profile of the normal and early malignancy is shown to emphasize their diagnostic potential in different malignancies. ** represents mucin expression under physiological conditions and the corresponding (+) sign represents further upregulation in cancer. The (-) sign shows non-detectable or lower expression under normal conditions and the (+) sign indicates the measurable increased/high expression of mucins. Red: early-stage expression profile; Green: mucin expression under normal conditions. The Illustrations in the figure were created with the help of BioRender tool.

Figure 2

Analysis of expression profile of mucins in cancer patients. The genetic and epigenetic changes trigger oncogenic progression in different organs, which lead to the expression of disease-specific proteins including mucins. For early detection of cancers with mucin upregulation (as shown in step 1), liquid biopsies are collected using different methods (step 2). In step 3, the collected liquid biopsies are analyzed for genomic, transcriptomic, and proteomic profiling. Analyses of genomic alterations and molecular expression profiles are being increasingly used for detailed characterization of tumors. On the other hand, liquid biopsies such as serum and body fluids are considered convenient and suitable for the early diagnosis of cancers. These liquid biopsies can be evaluated for mucin expression and their post-translation modifications for early cancer detection. The Illustrations in the figure were created with the help of BioRender tool.