Gautam Shailendra K, Khan Parvez, Natarajan Gopalakrishnan, Atri Pranita, Aithal Abhijit, Ganti Apar K, Batra Surinder K, Nasser Mohd W, Jain Maneesh
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cancers (Basel). 2023 Mar 7;15(6):1640. doi: 10.3390/cancers15061640.
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.
早期检测与癌症患者生存率的提高显著相关。到目前为止,仅有有限数量的生物标志物被证实可用于早期诊断癌症。考虑到在美国导致超过50%死亡的主要癌症类型,我们讨论了目前在肺癌、乳腺癌、卵巢癌、结肠癌、前列腺癌、肝癌和胰腺癌早期检测方面所做的努力,以突出粘蛋白糖蛋白在癌症诊断中的重要性。由于在大多数上皮恶性肿瘤发生致癌转化后,粘蛋白失调是最早出现的事件之一,这些高分子量糖蛋白被认为是生物标志物开发的潜在候选物。粘蛋白的诊断潜力主要归因于其表达失调、糖基化改变、剪接以及诱导自身抗体的能力。分泌型和脱落型粘蛋白通常在患者的血清、体液和肿瘤活检组织中被检测到。例如,CA125,也称为MUC16,是用于诊断卵巢癌的生物标志物之一,目前正在针对其他恶性肿瘤进行研究。同样,分泌型粘蛋白MUC5AC是胰腺癌的潜在生物标志物。此外,抗粘蛋白自身抗体和包裹有粘蛋白的外泌体为早期癌症诊断的生物标志物开发开辟了新途径。在这篇综述中,我们讨论了粘蛋白在上皮性癌症中的诊断潜力,并为开发基于粘蛋白的早期癌症检测生物标志物组合提供了证据和理论依据。