Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer

Abstract

BACKGROUND

Gastric cancer is a global health concern that poses a significant threat to human well-being.

AIM

To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer.

METHODS

Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined.

RESULTS

The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients.

CONCLUSION

CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.

Key Words: Biomarkers, Serum, Gastric cancer, Diagnostic value

Core Tip: This study provides a theoretical basis for clinical screening programs for patients with gastric cancer. In the future, the combined detection of carbohydrate antigens (CA) 724, carcinoembryonic antigen, CA242, and CA19-9 could complement the clinical diagnosis.

INTRODUCTION

Gastric cancer is a global health concern that poses a significant threat to human well-being. According to statistics from the World Health Organization and national cancer research agencies, over one million patients are newly diagnosed with gastric cancer each year, ranking it as the fifth most common malignancy worldwide. The high mortality rate associated with gastric cancer is attributable primarily to late-stage detection in most cases, making it the third leading cause of cancer-related deaths. Typically, originating from the mucosal cells of the stomach, these cells may undergo malignant transformation after prolonged exposure to certain carcinogenic factors. Adenocarcinoma is the most prevalent pathological type of gastric cancer. If detected early and treated surgically, the five-year survival rate for gastric cancer can reach 90%-100%, underscoring the critical importance of early diagnosis in improving survival outcomes. However, due to the lack of characteristic symptoms in the early stages, many patients are diagnosed only when the disease has advanced, which is significantly complicated, and treatment efforts are challenging. In the advanced stages of gastric cancer, even with comprehensive treatment approaches, including surgery, chemotherapy, and radiotherapy, the five-year survival rate remains below 30%. This highlights the challenges and limitations inherent to the treatment of late-stage gastric cancer. In recent years, with changes in lifestyle and social environment, there has been an upward trend in the annual incidence of gastric cancer worldwide, a phenomenon that has garnered widespread international attention[1]. In recent years, due to changes in the social environment, the annual incidence of gastric cancer has increased worldwide. According to a relevant statistical survey, the incidence of gastric cancer ranks fifth, and mortality ranks third among malignant tumors worldwide. In China, the incidence of gastric cancer is the second highest among malignant tumors, and its mortality rate is the third highest. The morbidity and mortality rates of gastric cancer in China are higher than international levels, indicating the severity of the prevention and treatment of gastric cancer in China[2-5].

Early diagnosis and treatment are important to improve the prognosis of patients with gastric cancer. However, owing to the lack of obvious symptoms in the early stages, the detection rate is low, and treatment is often delayed, which affects the prognosis of patients. Therefore, effective screening methods are needed to detect and intervene as early as possible to improve the prognosis of patients. The value of the early diagnosis of gastric cancer is primarily reflected in several aspects. Enhanced resection rates: Early stage gastric cancer lesions are comparatively small, rendering surgical removal less challenging and swifter postoperative recovery, contributing to an improved quality of life for patients. Reduced Risk of Recurrence: An Early diagnosis allows prompt treatment, diminishes the likelihood of cancer cell dissemination, and lowers the risk of postoperative recurrence. Prolonged Survival: Initiating treatment during the early stages of gastric cancer can significantly extend a patient's lifespan, thereby alleviating the burden on families and society. Improved Quality of Life: An Early diagnosis prevents exacerbation of the disease, mitigates patient suffering, and enhances the overall quality of life. Tumor markers are currently important indicators for the clinical screening of malignant tumors, which are produced by malignant tumor cells or the body acting on tumor cells. They have good application in the diagnosis, treatment, and prognostic assessment of malignant tumors. Currently, many tumor markers are used in clinical practice, including glycoproteins, enzymes, and hormones. Some indicators have been promoted and applied in physical examinations. However, owing to the complex biological changes in tumor occurrence and progression, there are differences in pathological tissue characteristics among malignant tumors, which also lead to differences in tumor marker changes, resulting in differences in sensitivity and specificity of the tumor markers. Tumor markers cannot be used as definitive diagnostic evidence and are usually used for auxiliary clinical diagnoses.

Serum biomarkers, such as carcinoembryonic antigen (CEA), cancer antigens CA724, CEA, CA242, and CA19-9, have been widely reported in the literature and applied in clinical practice for colorectal, ovarian, and pancreatic cancer[6-8]. CA724, CEA, CA242, and CA19-9 are tumor markers commonly used for clinical diagnosis and are widely applied in gastric cancer screening. Studies have confirmed that the combined diagnosis of CA724, CEA, CA242, and CA19-9 can improve the accuracy into detect patients with peritoneal pseudomyxoma[9]. To observe the application value of combined testing of CA724, CEA, CA242, and CA19-9, 80 patients with suspected gastric cancer between January 2020 and January 2023 were selected for the study.

MATERIALS AND METHODS

Study design and study participants

This was a case-control study in which patients in the observation group were from the Department of Gastroenterology in our hospital, while patients in the control group were selected from among other individuals with benign gastric diseases in the same department. Questionnaires and laboratory tests were administered to both the groups.

Inclusion and exclusion criteria

Inclusion Criteria: (1) Patients in the observation group were diagnosed with gastric cancer by pathological diagnosis, while patients in the control group were diagnosed with benign gastric diseases; (2) patients' age ranged from 40 to 80 years old; and (3) subjects in both groups were aware of the study and agreed to cooperate with the diagnosis. Exclusion criteria: (1) Patients with other malignant tumors; (2) patients with mental diseases; and (3) patients who resisted cooperation with the diagnostic study.

General information questionnaire

General information about the subjects was collected, including their name, age, sex, place of residence, marital status, income, and previous chronic disease prevalence.

Detection methods

Before blood collection, patients in both groups were instructed to fast beforehand and continue fasting on the morning of the blood collection day. Blood was drawn from the main vein at the elbow socket, and the volume of blood collected was controlled at approximately 4 mL/case. After collection, samples were sent to the laboratory within a specified timeframe. These samples underwent initial centrifugation at 3000 rpm for 5 min, and the supernatant was separated after continuous centrifugation. The separated samples were then frozen and stored at -20 ℃. For testing, immunoradiography enzyme-linked immunosorbent assay for CA724, CA19-9, CA242, and CEA were conducted using the MAGLUMIX8 Immunoassay Analyzer from New Industry. All samples were tested on the same day of collection. The threshold values of the biomarkers were determined based on the ranges provided by the manufacturers: CA19-9 > 30 U/mL; CA242 > 20 U/mL; CEA > 5 ng/mL; and CA724 > 12 U/mL.

Statistical analysis

The data were statistically analyzed using SPSS software (version 26.0). Continuous data were normally distributed and are expressed as means and percentages. The median (quartile) was used to describe continuous variables with skewed distribution, and numbers and percentages (%) were used to represent classified variables. Differences between the two groups of quantitative data were analyzed using t-tests. Multiple sets of data were analyzed using ANOVA. All the analyses were carried out at the test level of α = 0.05, and the difference was considered to be statistically significant when P < 0.05.

RESULTS

General information on the study population

Eighty cases of patients diagnosed with gastric cancer admitted to our hospital from January 2020 to January 2023 were selected as the observation group: 42 males and 38 females, aged 40-80 years old, with an average age of 60.15 ± 4.25 years old. Among them, 32 cases were in Stage I, 24 cases in Stage II, 14 cases in Stage III, and 10 cases in Stage IV. Another 80 cases of benign gastric diseases admitted to the hospital during the same period were selected as the control group: 41 men and 39 women, aged 40-80 years old, with an average age of 61.38 ± 5.44 years old. Among them, there were 29 cases of gastric polyps, 28 cases of chronic gastritis, and 33 cases of gastric ulcers. The differences between the two groups in terms of sex, age, and other general characteristics were not statistically significant (P > 0.05) and were comparable. This study was approved by our Ethics Committee (Table 1).

Table 1 General survey of case and control groups.

Variable	Observation group (n = 60)	Control group (n = 60)	P value
Age	60.15 ± 4.25	61.38 ± 5.44	0.191
Sex	42	41	0.874
Male
Female	38	39
Education	52	55	0.718
Junior high school and below
High school
College and above	17	13
Economic	11	12
≤ 2000	2	6	0.069
2001-2999	35	44
≥ 3000	43	30
Inheritance
Yes	32	15	0.003
No	48	65
Married
Yes	75	71	0.263
No	5	9

Comparison of the diagnostic results of different indicators against the results of pathologic tissues

The diagnostic results of CA724 in 160 patients were positive in 75 cases, negative in 85 cases, omitted in 19 cases and misdiagnosed in 14 cases. For CEA, the diagnostic results were positive in 78 cases, negative in 82 cases, omitted in 19 cases, and misdiagnosed in 17 cases. CA242 showed positive results in 83 cases, negative in 77 cases, omitted in 11 cases, and misdiagnosed in 14 cases. CA199 resulted in 79 positive cases, 81 negative cases, 19 omissions, and 18 misdiagnosed cases. The diagnostic results of the combined examination of CA724, CEA, CA242, and CA19-9 were positive in 81 cases, negative in 79 cases, omitted in one case, and misdiagnosed in two cases. The control comparison of the diagnostic results of the different indexes with the results of the pathologic tissues is shown in Table 2.

Table 2 Comparison of the diagnostic results of different indicators against the results of pathologic tissues.

Groups	CA724		CA19-9		CA242		CEA		Combined detection		Total
	Positive	Negative	Positive	Negative	Positive	Negative	Positive	Negative	Positive	Negative
Positive	61	19	61	19	69	11	61	19	79	1	80
Negative	14	66	17	63	14	66	18	62	2	78	80
Total	75	85	78	82	83	77	79	81	81	79	160

CEA: Carcinoembryonic antigen.

Differences in findings between the two screening methods

As shown in Table 3, the specificity, sensitivity, negative predictive value, and accuracy of the positive predictive value of the combined CA242, CA724, CEA, and CA19-9 assays were considerably higher than those of the CA242, CA724, CEA, and CA19-9 assays alone (P < 0.05).

Table 3 Difference in findings (%).

Groups	Sensitivity	Specificity	Accuracy	Positive predictive value	Negative predictive value
CA724	76.25	82.50	79.37	81.33	77.65
CA19-9	76.25	78.75	77.50	78.21	76.83
CA242	86.25	82.50	84.38	83.13	85.71
CEA	86.25	77.50	76.88	77.22	76.54
Combined detection	98.75	97.50	98.13	97.53	98.73
F	16.38	18.24	16.37	19.63	17.04
P value	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

CEA: Carcinoembryonic antigen.

Differences in serum tumor marker levels between patients with gastric cancer and patients with benign gastric disease. The serum levels of CA724, CEA, CA242, and CA19-9 in patients with gastric cancer were significantly higher than those in patients with benign gastropathy (P < 0.05; Table 4).

Table 4 Differences in serum tumor marker levels between patients with gastric cancer and patients with benign gastric disease.

Groups	CA724	CA19-9	CA242	CEA
Observation group	17.45 ± 1.25	16.83 ± 1.92	30.15 ± 4.45	27.92 ± 5.26
Gontrol group	1.63 ± 0.37	1.45 ± 0.25	3.82 ± 0.49	4.75 ± 0.44
t	17.28	15.66	11.63	19.02
P value	< 0.001	< 0.001	< 0.001	< 0.001

CEA: Carcinoembryonic antigen.

DISCUSSION

Gastric cancer is a common malignant tumor in clinical practice and its occurrence is closely related to multiple factors, including Helicobacter pylori infection, precancerous lesions, genetic factors, dietary habits, and environmental factors. Helicobacter pylori infection has been confirmed to be an important cause of gastric cancer, leading to chronic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia. Under the influence of poor dietary habits and environmental factors, it gradually develops into gastric cancer[10,11]. Dietary habits are also strongly linked to the occurrence of gastric cancer. The intake of excessively smoked foods, moldy substances, salted foods, and excessive salt increases the risk of gastric cancer. Additionally, gastric cancer has a genetic predisposition. Individuals with a family history of gastric cancer having a two- to three-fold higher risk of developing the disease than the general population. Most patients with early gastric cancer have no obvious symptoms, while a small number may experience abdominal distension and indigestion. These symptoms are often not easily detected by patients, and as the disease progresses, patients experience upper abdominal pain and weight loss. In advanced stages, it can induce anemia, anorexia, and emaciation. In the general population, patients experiencing upper abdominal pain, anorexia, weight loss, or palpable abdominal masses should seek medical attention as soon as possible. Early diagnosis and treatment are important to improve patient prognosis[12-14]. Gastric cancer diagnosis is relatively straightforward; however, many patients in the early stages have no symptoms or mild symptoms, such as upper abdominal discomfort and belching. These symptoms often go unnoticed by patients; therefore, the detection rate for early gastric cancer is low. As the disease progresses, when patients experience noticeable digestive tract symptoms, surgical treatment is not ideal. Adjuvant radiotherapy and chemotherapy can only extend patient survival time but still results in a low five year survival rate[15,16]. Therefore, effective screening methods are required for early diagnosis and treatment.

The clinical diagnosis of gastric cancer mainly relies on pathological tissue biopsy as the gold standard, with endoscopic biopsy demonstrating good results[17-19]. However, this method is invasive and cannot be widely applied for primary screening, which limits its utility. Imaging techniques, such as ultrasound, computed tomography, and magnetic resonance imaging also have certain applications in gastric cancer screening; however, they also have limitations. Tumor-specific macromolecule carbohydrate antigens (CA) are tumor-associated antigens commonly used in the clinical screening of gastric cancer. Among these, CA724, CEA, CA242, and CA19-9 are nonspecific tumor markers that are not elevated in healthy individuals with serum levels below 6 U/mL. However, they can be elevated in patients with digestive tract or ovarian cancers. They are typically used in clinical screening for gastric cancer and various digestive tract malignancies, having high diagnostic value for gastric cancer, non-small cell lung cancer, and ovarian mucinous cystadenocarcinoma, and moderate diagnostic value for colorectal cancer and pancreatic cancer. Clinical studies have found that serum CA724 levels are notably elevated in patients with gastric, colorectal, ovarian, lung, and breast cancers. CA242 is a mucin glycoprotein that is primarily recognized by the monoclonal antibody C242 obtained using hybridoma technology. Its expression level is low in healthy individuals, but high in non-squamous malignant tumors. It has a good application value in the auxiliary diagnosis of pancreatic, colorectal, and gastric cancers. CA199 is a novel tumor marker with a high sensitivity for gastrointestinal tumors. The levels of CA19-9 in pancreatic cancer, hepatobiliary system cancer, gastric cancer, and colorectal cancer were 683, 535, 279, and 115 times higher than the normal mean values, respectively. Therefore, it has a high diagnostic value for the clinical diagnosis of gastric cancer. CEA is a tumor-associated antigen and an acidic glycoprotein with characteristics of the human embryonic antigen. It is also a broad-spectrum tumor marker. The serum concentration of CEA in healthy individuals is extremely low, whereas it is higher in patients with gastric, liver, and esophageal cancers, making it a long-standing marker for malignant tumor screening. CEA mainly exists on the surface of tumor cells differentiated from endodermal cells and can enter bodily fluids through the cell membrane. CEA can be detected in various body fluids, such as serum, cerebrospinal fluid, gastric juice, and urine. Previously, clinical medicine has been used as a specific diagnostic indicator for colorectal cancer. However, with the deepening of clinical research, it has been found that the expression level of CEA tends to increase in patients with other malignant tumors. Therefore, although CEA is not used as a diagnostic index specific for malignancy, it has good application in the differential diagnosis of malignant tumors and the evaluation of its efficacy. This study showed that serum CA724, CEA, CA242, and CA19-9 levels in patients with gastric cancer were significantly higher than in those patients with benign stomach disease (P < 0.05). This indicates that CA724, CEA, CA242, and CA19-9 are highly expressed in gastric cancer patients and can be used as auxiliary clinical diagnostic markers.

Clinical studies have shown that although tumor marker tests are sensitive, they lack specificity. Therefore, the accuracy of the clinical diagnosis can be significantly improved by combining several tests. For example, in a study by Wang et al[20], the combination of CA724, CEA, CA242, and CA19-9 tests increased the positivity rate of gastric cancer screening, which is consistent with the results of our study. In another study by Liang et al[9], the combination of CA724, CEA, CA242, and CA19-9 tests reduced the rate of missed and misdiagnosed cases, which is consistent with the conclusions of this study. In a study by Li et al[21], the accuracy of the CA724, CEA, CA242, and CA19-9 combined tests was similar to that of the biopsy results and improved patient satisfaction in gastric cancer screening. A combination of tests can play a synergistic diagnostic role, thereby improving the accuracy of clinical diagnosis. Among the 160 patients in this study: 75 tested positive for CA724, 85 negative, 19 missed, and 14 misdiagnosed; 78 were positive for CEA, 82 negative, 19 missed, and 17 misdiagnosed; 83 were positive for CA242, 77 negative, 11 missed, and 14 misdiagnosed; 79 were positive for CA19-9, 81 negative, 19 missed, and 18 misdiagnosed; and 81 were positive for CA724, CEA, CA242, and CA19-9 combined tests, 79 negative, one missed, and two misdiagnosed. The sensitivity of CA724 was 76.25%, specificity was 82.50%, accuracy was 79.37%, positive predictive value was 81.33%, and negative predictive value was 77.65%; the sensitivity of CEA was 86.25%, specificity was 77.50%, accuracy was 76.88%, positive predictive value was 77.22%, and negative predictive value was 76.54%; the sensitivity of CA242 was 86.25%, specificity was 82.50%, accuracy was 84.38%, positive predictive value was 83.13%, and negative predictive value was 85.71%; the sensitivity of CA19-9 was 76.25%, specificity was 78.75%, accuracy was 77.50%, positive predictive value was 78.21%, and negative predictive value was 76.83%; the sensitivity of CA724, CEA, CA242, and CA19-9 combined tests was 98.75%, specificity was 97.50%, accuracy was 98.13%, positive predictive value was 97.53%, and negative predictive value was 98.73%. Compared to individual CA724, CEA, CA242, and CA19-9 testing, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the CA724, CEA, CA242, and CA19-9 combined tests were significantly higher (P < 0.05), indicating that this combination test has high diagnostic accuracy and can reduce missed and misdiagnosed cases to promote early diagnosis and treatment in patients. However, owing to the small sample size of this study, further multicenter randomized controlled studies with larger sample sizes are needed to improve the credibility of the conclusions.

CONCLUSION

In conclusion, the combination of CA724, CEA, CA242, and CA19-9 can improve the diagnostic accuracy of gastric cancer. The combined detection effect is notably superior to that of CA724, CEA, CA242, and CA19-9 individually, which can improve the efficacy of screening. The practical significance is substantial, making it a viable option for clinical application and potential promotion.

ARTICLE HIGHLIGHTS

Research background

In recent years, the incidence of gastric cancer has been increasing year by year due to changes in people's lifestyle and dietary structure. The early symptoms of gastric cancer are relatively occult, and some patients may experience abdominal pain, nausea, and other symptoms that are often misdiagnosed as simple gastritis or other diseases, resulting in delayed diagnosis and treatment. Therefore, it is crucial to prioritize the diagnosis of gastric cancer.

Research motivation

The aim of this study was to explore the values of combined detection of the tumor markers for diagnosing gastric cancer.

Research objectives

Eighty patients with suspected gastric cancer admitted between January 2023 and January 2023 were surveyed using a questionnaire to obtain basic information, and venous blood was collected for testing.

Research methods

Between January 2020 and January 2023, 80 patients diagnosed with gastric cancer were selected from our hospital were selected as the observation group. The sex and age of patients in the observation group were matched with those in the control group by 1:1, including 80 patients with benign gastric diseases treated at our hospital during the same period. Venous blood of patients with gastric cancer was collected, and serum was separated and stored at 20 °C for testing. Samples were tested using a MAGLUMIX8 immunoanalyzer (New Industries). The carbohydrate antigens (CA) 724, CA199, CA242, and carcinoembryonic antigen (CEA) levels were determined using immunoradiometric and enzyme-linked immunosorbent assays.

Research results

In this study, we found that the mean serum levels of CA724, CEA, CA242, and CA19-9 in patients with gastric cancer were notably higher than those in the non-gastric cancer control group. The specificity, sensitivity, negative predictive value, and accuracy of the combined detection of CA724, CEA, CA242, and CA19-9 in the observation group were higher than those of CA724, CEA, CA242, and CA199 individual detection. The combined detection of CA724, CEA, CA242, and CA19-9 has high diagnostic accuracy and can reduce the occurrence of missed or misdiagnosed cases, promoting early diagnosis and treatment.

Research conclusions

Combined testing with CA724, CEA, CA242, and CA19-9 has high diagnostic accuracy, which can reduce the occurrence of missed or misdiagnosed cases and promote early diagnosis and treatment. However, owing to the small sample size of this study, further evidence is needed to support its widespread use.

Research perspectives

In this study, the levels of CA724, CEA, CA242, and CA19-9 in patients with gastric cancer were compared to those in patients without gastric cancer. To analyze the value of the combined detection of CA724, CEA, CA242, and CA19-9 and to provide a theoretical basis for the clinical screening of patients with gastric cancer.