Current status of colorectal cancer tumor marker research

  Colorectal cancer is the fourth most common malignancy worldwide. in 2002, there were approximately 1 million cases of colorectal cancer and 530,000 deaths worldwide. In the United States, colorectal cancer is the second most deadly disease among cancer-related deaths. The incidence of colorectal cancer in China is on the rise, and according to the survey results in 2000, the incidence of colorectal cancer in major cities such as Beijing and Shanghai has risen to the 2nd or 3rd place in China. At present, colonoscopy has the highest sensitivity and specificity for colorectal cancer examination, but due to the high cost, pain and operation requirements, many patients are willing to undergo this examination, which causes many patients to delay until the late stage. Tumor markers have the advantages of minimally invasive, convenient detection, low cost and easy census, which can be applied to colorectal cancer screening, diagnosis, prognosis and treatment monitoring, etc. However, no ideal tumor markers have been found yet, and currently tumor markers are one of the hot spots of research in life sciences.  Protein complex 1, carcinoembryonic antigenCEA: CEA is a large molecule glycoprotein with molecular weight of 200ku, and elevated serum CEA level has a certain relationship with colorectal cancer stage. Dukes’ A, B, C, and D accounted for 3%, 25%, 45%, and 65%, respectively. A Swedish study of 70,000 people showed that a CEA above 5.6 ng/ml strongly suggested colorectal cancer (OR 7.9, 95% confidence interval). Thirty percent of subjects with elevated CEA in their blood samples were diagnosed with colorectal cancer within two years, but the majority (66%) of subjects diagnosed with colorectal cancer within two years had a CEA within the normal range. Although the specificity of CEA in this test was 99%, the sensitivity was very low, so CEA is not suitable as a mass screening indicator. In addition, a Korean study of 2,230 colorectal cancer patients showed that preoperative CEA levels were an important independent prognostic variable, with increased preoperative CEA levels associated with decreased five-year survival rates. In general, CEA gradually decreases to normal level 4C6 weeks after surgery. If CEA level does not decrease after colorectal cancer surgery, it indicates incomplete surgery, and if it increases again, it indicates tumor recurrence or metastasis, and about 75% of patients with recurrent colorectal cancer have increased CEA level. Therefore, CEA can be used as a monitoring indicator after colorectal cancer surgery. A recent study reported that positive CEA mRNA in venous blood was more than 80% accurate in predicting liver metastasis and local recurrence, but the sensitivity was only 30% and 9%, respectively; moreover, CEA level in mesenteric venous blood is a sensitive marker for liver metastasis with a sensitivity of 95%, and it is also a specific indicator for predicting 5-year survival rate of patients with a specificity of 84%. The latest NCCN guidelines for colorectal cancer also recommend CEA every 3 months for 2 years and every 6 months for 3-5 years for patients with stage T2 or larger lesions. In conclusion, CEA is the most commonly used and valuable tumor marker for colorectal cancer at present.  2.Survivin: Survivin is a member of the newly discovered inhibitor of apoptosis protein (IAP) family. It is undetectable in most normally differentiated tissues and is highly expressed in developing embryonic tissues and rapidly dividing cells. Apoptosis, also known as programmed cell death, is a highly conserved, tightly regulated cellular “suicide” that occurs in a specific space and time during cell evolution. Apoptosis is essential for the development and maintenance of homeostasis in multicellular organisms, especially in the modelling of embryonic development, the fine regulation of cell numbers and the clearance of potentially dangerous cells, and excessive or reduced apoptosis is the pathophysiological basis for the pathogenesis of many diseases. The evidence that defective apoptosis leads to tumorigenesis is compelling, and the imbalance between cell proliferation and apoptosis may be an important underlying cause in colorectal carcinogenesis, with numerous evidence suggesting that many molecules such as p53 and bcl-2 are involved in the regulation of apoptosis during colorectal carcinogenesis. The highly conserved family of anti-apoptotic genes encoding inhibitory apoptotic proteins (IAPs) is widely expressed in various malignancies and plays an important role in controlling apoptosis. survivin molecule, as a member of the family of inhibitory apoptotic proteins (IAPs), is a novel anti-apoptotic gene that is widely expressed in colorectal cancer and several other malignancies. Studies have shown that survivin mRNA expression is significantly higher in colorectal cancer specimens than in adjacent normal tissues.