Mucins as Potential Biomarkers for Early Detection of Cancer.
Mucins as Potential Biomarkers for Early Detection of Cancer.
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早期癌症检测是治疗癌症患者的一个挑战。值得注意的是，乳腺癌、肺癌、肝癌、胰腺癌、卵巢癌和结肠癌占每年总发病率和死亡率的50%以上，这可以通过早期发现来降低。由于粘蛋白在这些癌症的早期进展过程中高度上调，一些研究已经探索了粘蛋白作为潜在的生物标志物。由于其膜结合和分泌性质，粘蛋白已在癌症患者的肿瘤活检和液体活检中检测到，包括血液和尿液样品。我们在这里汇总了以前的研究，倡导使用粘蛋白作为早期检测癌症的潜在生物标志物，并讨论了与其他生物标志物和检测方式相结合的粘蛋白生物标志物的使用相关的机遇和挑战。早期发现与癌症患者生存率的提高显著相关。到目前为止，已经验证了有限数量的生物标志物来早期诊断癌症。考虑到导致美国50%以上死亡的主要癌症类型，我们讨论了对肺癌，乳腺癌，卵巢癌，结肠癌，前列腺癌，肝癌和胰腺癌的早期检测的持续努力，以突出粘蛋白糖蛋白在癌症诊断中的重要性。由于粘蛋白失调是致癌转化后大多数上皮恶性肿瘤中最早的事件之一，因此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者。粘蛋白的诊断潜力主要归因于其表达失调、糖基化改变、剪接和诱导自身抗体的能力。分泌和脱落粘蛋白通常在患者的血清、体液和肿瘤活检中检测到。例如，CA125，也称为MUC16，是用于诊断卵巢癌的生物标志物之一，目前正在研究其他恶性肿瘤。类似地，MUC5AC，一种分泌性粘蛋白，是胰腺癌的潜在生物标志物。此外，抗粘蛋白自身抗体和粘蛋白包装的外泌体开辟了用于早期癌症诊断的生物标志物开发的新途径。在这篇综述中，我们讨论了粘蛋白在上皮癌中的诊断潜力，并为开发用于早期癌症检测的基于粘蛋白的生物标志物小组提供了证据和理论基础。
Early cancer detection is a challenge in treating cancer patients. Remarkably, carcinomas of the breast, lung, liver, pancreas, ovary, and colon contribute to more than 50% of total incidences and mortality annually, which could be reduced by early detection. As mucins are highly upregulated during the early progression of these cancers, several studies have explored mucins as potential biomarkers. Due to their membrane-bound and secretory nature, mucins have been detected in tumor biopsies and liquid biopsies of cancer patients, including blood and urine samples. We compiled here previous studies advocating for the use of mucins as potential biomarkers for the early detection of cancer and discuss the opportunities and challenges related to the use of mucin biomarkers in combination with other biomarkers and detection modalities. 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.
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