Department of Nuclear Medicine, Jilin University Second Hospital [Combined Application of Tumor Markers] Issue 7 - Gastric Tumor Marker Panel

Gastric cancer refers to an epithelial malignant tumor that originates in the stomach. According to the latest data from China in 2023, the incidence of gastric cancer ranks third among various malignant tumors (Figure 1). There are about 1.2 million new cases of gastric cancer worldwide each year, of which China accounts for about 40%. The proportion of early gastric cancer in my country is very low, only about 20%, and most of them are already in the advanced stage when discovered, with an overall 5-year survival rate of less than 50%. At present, tumor markers are widely used in clinical diagnosis, providing dynamic observation of tumor occurrence and development, clinical efficacy evaluation and patient prognosis, thereby improving the detection rate and accuracy of differential diagnosis.

Figure 1 Number of cancer cases in my country in 2023

Currently, the commonly used tumor markers for diagnosing gastric cancer include alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), pepsinogen I detection (PGⅠ), pepsinogen II detection (PGⅡ), PGⅠ/PGⅡ ratio, carbohydrate antigen 50 (CA50), carbohydrate antigen 242 (CA242), etc.

AFP

Alpha-fetoprotein (AFP) is a glycoprotein that belongs to the albumin family and is mainly synthesized by fetal liver cells and yolk sac. AFP has a high concentration in fetal blood circulation, which decreases after birth and is extremely low in adult serum. It is closely related to the occurrence and development of various tumors and can be used as a positive detection indicator for various tumors.

Gastric cancer with high AFP levels accounts for about 2.7% to 8% of gastric cancers . Gastric cancer with elevated serum AFP and other diseases such as hepatitis, cirrhosis, hepatocellular carcinoma and germ cell malignancies can be excluded. It is highly invasive and often accompanied by liver and lymph node metastasis. In addition, some other diseases, such as pancreatic cancer, lung cancer, congestive hepatomegaly, telangiectasia, congenital tyrosinosis, etc., can also show varying degrees of elevated alpha-fetoprotein. AFP can not only help detect early signs of tumors, but also assist in early diagnosis, thereby improving the efficacy.

CEA

As a broad-spectrum tumor marker, CEA is elevated in many tumors, including digestive system tumors, breast cancer, lung cancer, etc. CEA has a relatively high sensitivity in gastrointestinal tumors. When CEA is elevated, it is more likely to be a gastrointestinal tumor. The positive rate and elevated level of CEA are also closely related to the stage and prognosis of the tumor . For example, if a gastric cancer patient has a very high CEA level before surgery, the patient may have a later stage of the disease and the survival expectation after surgery may not be ideal. CEA can also be used as an indicator for efficacy evaluation. Usually, the CEA level of cancer patients will drop significantly after surgery. If CEA rises again during reexamination, it often indicates tumor recurrence. In some patients receiving comprehensive treatments such as chemotherapy, CEA can also be used as an indicator for efficacy evaluation.

Carbohydrate antigen 125

CA125 is the most commonly used tumor marker for ovarian cancer, but it also has a good auxiliary diagnostic role in breast cancer, pancreatic cancer and digestive system cancer. It has a higher sensitivity in digestive system tumors, especially when the tumor invades the peritoneum and metastasizes, the CA125 level tends to increase (Figure 2) . In other words, if the patient's CA125 level is elevated, laparoscopy should be considered to determine whether there is peritoneal metastasis.

Figure 2 Factors affecting the increase of CA125

Carbohydrate antigen 19-9 (CA19-9)

CA19-9 is also a commonly used tumor marker in digestive system tumors. When CA19-9 is combined with other tumor markers such as CEA, it can improve the sensitivity of diagnosing gastric cancer. In addition, CA19-9 can also be used as an independent risk factor for lymph node involvement, gastric cancer recurrence and metastasis . In other words, if a patient's CA19-9 is very high, there is a high possibility that he or she has lymph node metastasis.

Carbohydrate Antigen 72-4 (CA72-4)

CA72-4 is currently one of the best tumor markers for diagnosing gastric cancer. It has a high specificity for gastric cancer and a sensitivity of 28%-80%. If combined with CA19-9 and CEA, it can monitor more than 70% of gastric cancer. CA72-4 levels are significantly correlated with the stage of gastric cancer, and generally increase in stages III-IV of gastric cancer. For patients with gastric cancer with metastasis, the positive rate of CA72-4 is much higher than that of patients without metastasis.

CA72-4 levels can drop rapidly to normal after surgery. In 70% of recurrent cases, CA72-4 concentrations are the first to increase. Compared with other markers, the main advantage of CA72-4 is its high specificity in the differential diagnosis of benign lesions. Among many patients with benign gastric diseases, its detection rate is only 0.7%.

Pepsinogen (PGⅠ), (PGⅡ) and PGⅠ/PGⅡ ratio

Pepsinogen (PG) is mainly secreted by gastric chief cells and is an important indicator for evaluating gastric mucosal function. Pepsinogen includes two members: pepsinogen I (PGⅠ) and pepsinogen II (PGⅡ). Changes in serum PG are subclinical indicators of gastric cancer precursors. The lower the serum PGI/PGII ratio, the higher the incidence of gastric cancer . The ratio can also be used to determine whether other tests are needed (Figures 3 and 4).

Figure 3, Figure 4 Relationship between serum PG content and gastric cancer incidence**** and interpretation of PG screening results

Carbohydrate antigen 50 (CA50)

CA50 is the most commonly used carbohydrate antigen tumor marker. Because it is widely present in the pancreas, gallbladder, liver, stomach, colorectum, bladder, and uterus, it is a common tumor marker-related antigen. It can be used as an important indicator for auxiliary diagnosis of gastric cancer. It can be combined with other indicators such as CA724, CA199, PGI, and PGII to diagnose gastric cancer and improve the detection rate of gastric cancer.

The concentration of CA50 in gastric juice of patients with atrophic gastritis is significantly different from that of normal people. Atrophic gastritis is generally considered to be a high-risk period before cancer, so CA50 can be used as one of the diagnostic indicators for precancerous disease.

Carbohydrate Antigen 72-4 (CA72-4)

Carbohydrate antigen 72-4 (CA72-4) is a high molecular weight mucin that is used in combination with carcinoembryonic antigen, CA19-9, and CA125 for the diagnosis, monitoring, and prognosis of a variety of malignant tumors. A study showed that the total positive rate of CA72-4 in gastric cancer patients can reach 70% , which is higher than carcinoembryonic antigen (24.0%) and CA19-9 (27.0%).

The 2022 edition of the Chinese Medical Association's Gastric Cancer Diagnosis and Treatment Guidelines clearly states that elevated levels of CA72-4, carcinoembryonic antigen, and CA19-9 are helpful for the diagnosis of gastric cancer. AFP and CA125 can be further tested in some patients. CA125 has a certain diagnostic and prognostic value for peritoneal metastasis and AFP has a certain diagnostic and prognostic value for special pathological types of gastric cancer. CA242, CA50, pepsinogen I, and pepsinogen II are sensitive and specific for the detection of some gastric malignancies.

In summary, although a single test of common tumor markers has a high specificity and good diagnostic efficacy for a certain type of gastric cancer, in comparison, the combined detection of multiple tumor markers can greatly improve the sensitivity and specificity of diagnosis.

Author: Guan Yize

First review: Tai Jing

Final judge: Zhao Yinlong