Does glutathione reductase have an impact on the prognostic assessment of patients with gastric cancer?

 Gastric cancer (GC) is a malignant tumor of the gastric mucosal epithelium with a high incidence and low cure rate, and is one of the most common malignant tumors in the world, with adenocarcinoma accounting for 95% of the tissue types[1] . According to the latest statistics, gastric cancer accounts for 770,000 deaths and 1.09 million cases of gastric cancer diagnosed each year worldwide [2]. Helicobacter pylori is a tumorigenic factor of gastric cancer, and 40-60% of adults in China are infected with Helicobacter pylori, which is one of the reasons for the high incidence of gastric cancer in China [3]. There are no obvious clinical symptoms in the early stage of gastric cancer, and the diagnosis is often made at an advanced stage, and the 5-year survival rate of gastric cancer in China is less than 30% due to metastasis and drug resistance [4]. In China, the 5-year survival rate of gastric cancer is less than 30% due to cancer metastasis and drug resistance[4] . Traditional tumor markers, such as CEA, CA199, etc., are not suitable for the diagnosis of early gastric cancer due to the lack of specificity and sensitivity.

 

Glutathione reductase (GR) was first found in prokaryotes and eukaryotic cells of plants and animals, and in humans, it is mainly found in erythrocytes, monocytes, macrophages, and tissue cells of the heart, liver, and kidneys, and it is a monomeric riboflavin-type oxidoreductase [5], which is an important component of the human redox system. GR uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor to catalyze the formation of reduced glutathione (GSH) from oxidized glutathione (GSSG). This enzyme increases the ratio of GSH/GSSG and maintains a high level of GSH in the body, which is beneficial to the body's antioxidant activity[6] . At present, the clinical application of GR is mainly reported in hepatitis, cirrhosis and metastatic hepatocellular carcinoma [7-8], but the application of GR in gastric cancer patients has not been reported. In this study, 337 patients with gastric cancer were collected as the observation group and 135 healthy medical checkups were collected as the control group to compare the differences in serum GR activity concentration between the two groups, and to analyze the changes in serum GR activity concentration in patients with gastric cancer with different clinicopathological characteristics and the changes in GR activity concentration before and after surgery, with the aim of exploring the value of the application of GR in the assessment of prognosis of gastric cancer.

 

1 Information and methodology

1.1 General Information   

Ninety gastric cancer patients treated in Jiangxi Cancer Hospital from December 2018 to December 2019 and 247 gastric cancer patients treated in the Second Affiliated Hospital of Nanchang University from 2020 to 2021 were selected as the observation group, and 135 health checkups were selected as the control group.337 patients in the observation group included 212 males and 125 females, with a minimum age of 20 years old and a maximum age of 90 years old, and a mean age of (6136±11.08 years old). The minimum age of the patients was 20 years old, the maximum age was 90 years old, and the average age was 61.36±11.08 years old; the clinical stages were: 61 cases of Stage I (18.1%), 75 cases of Stage II (22.3%), 165 cases of Stage III (49.0%), and 36 cases of Stage IV (10.7%).There were 87 males in the control group, and the number of patients who had been treated in the control group was 137, and the number of patients who had undergone medical checkups was 135.

There were 48 female cases, with age ranging from 26 to 89 years old, and the average age was (48.00±14.32) years old. The correlation coefficient between age and GR activity was -0.26, with no statistically significant difference (P=0.639>0.05), and there was no statistically significant difference between gender and GR activity (P=0.383>0.05).

 

1.2 Testing equipment and reagents   

The GR testing equipment of Jiangxi Cancer Hospital was Hitachi 7600 (210) automatic biochemical analyzer, and the testing equipment of the Second Affiliated Hospital of Nanchang University was Canon TBA-FX8 automatic biochemical analyzer, and the reagents were provided by Jiangxi Lecheng Technology Co. All the reagents were provided by Jiangxi Lecheng Science and Technology Co.

 

1.3 Inclusion criteria   

Inclusion criteria of the observation group: (1) meeting the clinical diagnostic criteria of gastric cancer and diagnosed as gastric cancer; (2) normal liver and kidney functions;

(3) No other tumor disease except gastric cancer . Inclusion criteria for the control group: (1) people who came to the hospital for health checkups; (2) normal liver and kidney functions; (3) no tumors.

 

1.4 Methodology

1.4.1 Information collection   

Gastric cancer patients and health checkups treated in Jiangxi Provincial Cancer Hospital and the Second Affiliated Hospital of Nanchang University from December 2018 to December 2021 were retrospectively analyzed, and the observation and control groups were screened according to the inclusion criteria.

 

1.4.2 Analyzing the difference in GR activity between the observation and control groups   

Differences in GR activity were analyzed in 337 cases of gastric cancer in the observation group and 135 healthy controls.

1

.4.3 Analysis of different clinicopathological characteristics of the observation group

Differences in GR activity were analyzed in 337 cases of gastric cancer in the observation group with different age, gender and clinicopathological stages.

 

1.4.4 Statistical methods  

The collected data were statistically analyzed using SPSS 21.0 software. The P-P plot was used to test whether the data were normally distributed, and continuous variables were expressed as mean ± standard deviation (x ± s). Differences between the two groups were analyzed by independent samples t-test, differences between the observation group before and after surgery were analyzed by paired samples t-test, multiple comparisons were analyzed by one-way ANOVA, and correlation analyses were performed by Pearson's method, and differences were considered statistically significant if P<0.05.

 

2 Results

2.1 Comparison of serum GR activity between observation and control groups   

The P-P plot test showed that the GR activity data were normally distributed, as shown in Figure 1. Serum GR activity in the observation group (51.73±13.15)U/L, and in the control group (56.89±10.43)U/L, the difference was statistically significant (P=0.000<0.05), see Table 1.

 

2.2 Comparison of serum GR activity in patients with different clinicopathologic characteristics in the observation group  

It was found that there was no statistically significant difference between the serum GR activity and the age and gender of the patients (P>0.05), while there was a statistically significant difference between the serum GR activity and the clinical stage of the patients (P=0.000<0.05), as shown in Table 2.

 

2.3 Changes in GR activity before and after surgery and chemotherapy in the observation group   

The preoperative GR activity was higher than the postoperative GR activity in 74 patients with gastric cancer who underwent surgical treatment, and the difference was statistically significant (P<0.05). The difference was statistically significant (P<0.05).

 

3 Discussion

Gastric cancer is one of the most common malignant tumors in the digestive system. With the development of China's economy and the change of people's life style and dietary habits, the incidence rate and mortality rate of gastric cancer have been increasing year by year, and the trend of incidence of gastric cancer has been developing towards the younger age group [9]. The five-year survival rate of early gastric cancer is significantly higher than that of late gastric cancer, and early detection, diagnosis and treatment are of great significance in reducing the mortality rate and improving the prognosis of gastric cancer [10]. At present, the "gold standard" for the diagnosis of gastric cancer is gastroscopy and submucosal tissue biopsy, which is expensive, highly uncomfortable for patients in the process of detection, poorly accepted by patients, and unsuitable for large-scale clinical application. Tumor markers used to detect gastric cancer are mainly CEA, CA19-9 and CA72-4, but the sensitivity and specificity are not high in the general population, and they are mainly used for the detection of postoperative recurrence and metastasis [11].

 

GR is widely present in the human body and catalyzes the reduction of GSSG to GSH, which has the effect of enhancing the antioxidant, anti-inflammatory and antiproliferative properties of the body. The present study showed that the difference in serum GR activity concentration between gastric cancer patients and healthy subjects was statistically significant (P=0.000<0.05). Further analysis of serum GR activity concentration in gastric cancer patients with different clinicopathological characteristics showed that the difference in GR activity concentration between different ages and genders was not statistically significant (P>0.05), while the difference in GR activity concentration between different clinical stages was statistically significant (P<0.05), and the GR activity gradually increased with the progression of the disease, but the concentration of GR activity was significantly lower after the operation than that before the operation (P<0.05). However, the concentration of GR activity after surgery was significantly lower than that before surgery (P<0.05). These results suggested that serum GR activity concentration was not closely related to the development of gastric cancer. Oxygen free radicals can induce cell mutation, apoptosis, chromosomal aberrations and carcinogenesis[12] , and GR is an important component of the antioxidant system in the body.Yalcin Kekec et al.[13] showed that GR was significantly higher in gastric cancer tissues than in paracancerous tissues. In the present study, we analyzed the GR activity of 337 patients with gastric cancer in two tertiary hospitals, covering stages I, II, III, IV, preoperative and postoperative, and excluding the interference of liver function abnormalities and other tumors, so the analysis results have a good credibility. However, further basic research is needed to investigate the pathway through which GR promotes the development of gastric cancer.

 

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