Cytokeratin 18 (CK18) is a protein found within human cells, belonging to the family of intermediate filaments. These structural proteins are prevalent in epithelial cells, which line many organs and glands. The presence and levels of CK18 can provide insights into cellular health and disease processes, making it a valuable biomarker.
Cytokeratin 18 in Healthy Cells
In healthy cells, CK18 maintains cellular structure. It acts as an intermediate filament, a component of the cytoskeleton that provides internal scaffolding and mechanical strength. This protein helps cells withstand external stresses and maintain their shape. CK18 is found in the cytoplasm and perinuclear regions of many single-layered epithelial tissues, including the liver, lungs, kidneys, pancreas, and gastrointestinal tract. It works with cytokeratin 8, its complementary partner, to form a flexible network within these cells, contributing to tissue integrity.
Why Cytokeratin 18 is a Biomarker
CK18 gains significance as a biomarker because its fragments are released into the bloodstream when cells are damaged or undergo specific forms of cell death. When a cell dies, its plasma membrane breaks down, releasing cellular components, including CK18 and its fragments, into the bloodstream. This release allows for the detection of cell death in various tissues.
Two primary forms of CK18 are commonly measured: total cytokeratin 18 (M65) and caspase-cleaved cytokeratin 18 (M30). M65 assays measure all forms of CK18, indicating overall cell death, encompassing both apoptosis and necrosis. In contrast, the M30 assay specifically detects a neoepitope on CK18 created when the protein is cleaved by caspases, specifically caspase-3, during apoptosis. Therefore, M30 levels are specific indicators of apoptotic cell death. By measuring both M30 and M65, researchers and clinicians can gain insights into the predominant type of cell death occurring. For instance, if M65 levels are much higher than M30 levels, it may suggest that necrosis is the primary mode of cell death.
Cytokeratin 18 in Disease Detection
CK18 is recognized for its utility in identifying and monitoring medical conditions, particularly those involving damage to epithelial tissues. Its role is well-established in liver diseases. Elevated levels of CK18 (both M30 and M65) are associated with hepatocyte (liver cell) death, making them candidate markers for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). While liver biopsy remains the standard for diagnosing NASH, CK18 offers a less invasive alternative that can help distinguish NASH from simple fatty liver.
CK18 levels can also help assess the severity of liver damage and predict the progression of NAFLD. Increased CK18 fragment levels correlate with hepatocyte apoptosis and can predict the presence and severity of NASH. In acute liver injury, elevated CK18 levels also indicate active cell damage. For advanced liver disease patients, elevated M65 and M30 levels at admission indicate a less favorable prognosis. Beyond liver conditions, CK18 also has a supportive role in certain cancers. In breast cancer, for example, CK18 biomarkers can be useful for early prediction of response to chemotherapy. CK18 is consistently expressed in various epithelial cancers, particularly adenocarcinomas, and its altered expression can be associated with tumor progression.
Interpreting Cytokeratin 18 Levels
CK18 levels are typically measured through a blood test. A healthcare professional draws a small amount of blood, usually from a vein in the arm, which is then sent to a laboratory for analysis. No specific preparation, such as fasting, is generally required before the test.
Elevated levels of CK18 (M65 or M30) generally indicate active cell damage or cell death within epithelial tissues. However, CK18 is a supportive marker. It is not a standalone diagnostic tool, and its results should always be interpreted by a healthcare professional in conjunction with other clinical assessments, patient history, and relevant diagnostic tests.