1.Influencing factors and prognostic analysis of early recurrence after gastrectomy for gastric cancer: a national multicenter study
Jun LU ; Chenbin LYU ; Yi CAO ; Jie CHEN ; Sen LI ; Lisheng CAI ; Shuanhu WANG ; Fanghui DING ; Zhengrong LI ; Yuzhou ZHAO ; Fenglin LIU
Chinese Journal of Digestive Surgery 2025;24(3):350-356
Objective:To investigate the influencing factors and prognosis of early recurrence after gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 078 patients who underwent gastrectomy for gastric cancer at six medical centers across China, including Fudan University Shanghai Cancer Center et al, between January 2012 and June 2023 were collected. There were 1 449 males and 629 females, aged (59±11) years. Patients were classified as early recurrence and late recurrence based on the time of post-operative recurrence. Observation indicators: (1) comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types; (2) recurrence and metastasis of tumor; (3) survival of patients after postoperative recurrence of gastric cancer; (4) analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Multivariate analysis was conducted using the Logistic regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types. Among the 2 078 patients, 1 452 cases had early recurrence and 626 cases had late recurrence. There were significant differences in preoperative carcinoembryonic antigen, preoperative CA19-9, preoperative CA72-4, preoperative albumin, tumor diameter, neoadjuvant therapy, R 0 resection, combined organ resection, scope of gastric resection, nerve and vessel infiltration, degree of tumor differentiation, pathological N staging, pathological TNM staging between early and late recurrence patients ( P<0.05). (2) Recurrence and metastasis of tumor. Among the 2 078 patients, 200 cases had local recurrence, 1 213 cases had hematogenous metastases, 392 cases had distant lymph node metastases, and 731 cases had peritoneal metastases. Among the 1 452 early recurrence patients, 142 cases had local recurrence, 834 cases had hematogenous metastases, 289 cases had distant lymph node metastases, and 507 cases had peritoneal metastases. Among the 626 late recurrence patients, 58 cases had local recurrence, 379 cases had hematogenous metastases, 103 cases had distant lymph node metastases, and 224 cases had peritoneal metastases. One patient may have multiple forms of recurrence and metastasis. There was no significant difference in the above indica-tors between early and late recurrence patients ( χ2=0.13, 1.74, 3.40, 0.14, P>0.05). (3) Survival of patients after postoperative recurrence of gastric cancer. All 2 078 patients were followed up until death after recurrence, with a follow-up time of 31(range, 9?147)months. The 1-, 2-, 3-, and 5-year overall survival rates after recurrence were 33.5%, 17.2%, 10.1%, and 3.3% in early recurrence patients, versus 44.2%, 21.6%, 12.8%, and 5.8% in late recurrence patients, respectively, showing a significant difference in overall survival after recurrence between the two groups ( hazard ratio=0.84, 95% confidence interval as 0.76?0.92, P<0.05). (4) Analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Results of multivariate analysis showed that combined organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ were independent risk factors for early recurrence after gastrectomy for gastric cancer ( odds ratio=1.31, 1.32, 1.34, 95% confidence interval as 1.01?1.70, 1.06?1.65, 1.05?1.71, P<0.05) and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection were independent protective factors for early recurrence ( odds ratio=0.61, 0.50, 0.38, 95% confidence interval as 0.49?0.76, 0.35?0.72, 0.25?0.58, P<0.05). Conclusions:Compared with patients with late recurrence after gastric cancer surgery, patients with early recurrence have a poor prognosis, in which liver metastases is more common. Combine organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ are independent risk factors for early recurrence, and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection are independent protective factors for early recurrence after gastrectomy for gastric cancer.
2.Influencing factors and prognostic analysis of early recurrence after gastrectomy for gastric cancer: a national multicenter study
Jun LU ; Chenbin LYU ; Yi CAO ; Jie CHEN ; Sen LI ; Lisheng CAI ; Shuanhu WANG ; Fanghui DING ; Zhengrong LI ; Yuzhou ZHAO ; Fenglin LIU
Chinese Journal of Digestive Surgery 2025;24(3):350-356
Objective:To investigate the influencing factors and prognosis of early recurrence after gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 078 patients who underwent gastrectomy for gastric cancer at six medical centers across China, including Fudan University Shanghai Cancer Center et al, between January 2012 and June 2023 were collected. There were 1 449 males and 629 females, aged (59±11) years. Patients were classified as early recurrence and late recurrence based on the time of post-operative recurrence. Observation indicators: (1) comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types; (2) recurrence and metastasis of tumor; (3) survival of patients after postoperative recurrence of gastric cancer; (4) analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Multivariate analysis was conducted using the Logistic regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types. Among the 2 078 patients, 1 452 cases had early recurrence and 626 cases had late recurrence. There were significant differences in preoperative carcinoembryonic antigen, preoperative CA19-9, preoperative CA72-4, preoperative albumin, tumor diameter, neoadjuvant therapy, R 0 resection, combined organ resection, scope of gastric resection, nerve and vessel infiltration, degree of tumor differentiation, pathological N staging, pathological TNM staging between early and late recurrence patients ( P<0.05). (2) Recurrence and metastasis of tumor. Among the 2 078 patients, 200 cases had local recurrence, 1 213 cases had hematogenous metastases, 392 cases had distant lymph node metastases, and 731 cases had peritoneal metastases. Among the 1 452 early recurrence patients, 142 cases had local recurrence, 834 cases had hematogenous metastases, 289 cases had distant lymph node metastases, and 507 cases had peritoneal metastases. Among the 626 late recurrence patients, 58 cases had local recurrence, 379 cases had hematogenous metastases, 103 cases had distant lymph node metastases, and 224 cases had peritoneal metastases. One patient may have multiple forms of recurrence and metastasis. There was no significant difference in the above indica-tors between early and late recurrence patients ( χ2=0.13, 1.74, 3.40, 0.14, P>0.05). (3) Survival of patients after postoperative recurrence of gastric cancer. All 2 078 patients were followed up until death after recurrence, with a follow-up time of 31(range, 9?147)months. The 1-, 2-, 3-, and 5-year overall survival rates after recurrence were 33.5%, 17.2%, 10.1%, and 3.3% in early recurrence patients, versus 44.2%, 21.6%, 12.8%, and 5.8% in late recurrence patients, respectively, showing a significant difference in overall survival after recurrence between the two groups ( hazard ratio=0.84, 95% confidence interval as 0.76?0.92, P<0.05). (4) Analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Results of multivariate analysis showed that combined organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ were independent risk factors for early recurrence after gastrectomy for gastric cancer ( odds ratio=1.31, 1.32, 1.34, 95% confidence interval as 1.01?1.70, 1.06?1.65, 1.05?1.71, P<0.05) and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection were independent protective factors for early recurrence ( odds ratio=0.61, 0.50, 0.38, 95% confidence interval as 0.49?0.76, 0.35?0.72, 0.25?0.58, P<0.05). Conclusions:Compared with patients with late recurrence after gastric cancer surgery, patients with early recurrence have a poor prognosis, in which liver metastases is more common. Combine organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ are independent risk factors for early recurrence, and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection are independent protective factors for early recurrence after gastrectomy for gastric cancer.
3.High expression of CDKN3 promotes migration and invasion of gastric cancer cells by regulating the p53/NF-κB signaling pathway and inhibiting cell apoptosis.
Yi ZHANG ; Yu SHEN ; Zhiqiang WAN ; Song TAO ; Yakui LIU ; Shuanhu WANG
Journal of Southern Medical University 2025;45(4):853-861
OBJECTIVES:
To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients.
METHODS:
We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3. The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay, CCK-8 assay, TUNEL staining, flow cytometry, and Western blotting.
RESULTS:
CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (P<0.05). High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis (P<0.01). Enrichment analyses suggested a probable association of CDKN3 with apoptosis. In MGC-803 cells, CDKN3 knockdown significantly lowered migration and invasion capacities of the cells, while CDKN3 overexpression produced the opposite effects. TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues (P<0.01). CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells. CDKN3 overexpression down-regulated the expressions of p53, p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2.
CONCLUSIONS
CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis. CDKN3 overexpression promotes proliferation, invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.
Humans
;
Stomach Neoplasms/pathology*
;
Apoptosis
;
Signal Transduction
;
Tumor Suppressor Protein p53/metabolism*
;
Cell Movement
;
Cell Line, Tumor
;
NF-kappa B/metabolism*
;
Prognosis
;
Cyclin-Dependent Kinase Inhibitor Proteins/metabolism*
;
Cell Proliferation
;
Neoplasm Invasiveness
;
Male
;
Female
;
Dual-Specificity Phosphatases
4.Clinical study on the treatment of spleen deficiency and phlegm stasis syndrome in alcoholic cirrhosis with Qinggan Huashi Huoxue Decoction and conventional western medicine
Shuxian LI ; Shuanhu LIU ; Zhishan YAO ; Yuxiang MAO
International Journal of Traditional Chinese Medicine 2023;45(9):1086-1090
Objective:To evaluate the efficacy of Qinggan Huashi Huoxue Decoction combined with conventional Western medicine in the treatment of alcoholic cirrhosis with spleen deficiency and phlegm stasis syndrome.Methods:Randomized controlled trial. A total of 110 patients from Tangshan Fengrun District Hospital of Traditional Chinese Medicine from March 2020 to March 2022 were selected as observation objects and divided into 2 groups with 55 patients in each group by computer random drawing method. The control group was treated with conventional Western medicine, while the observation group was treated with Qinggan Huashi Huoxue Decoction on the basis of the control group treatment. Both groups were treated for 3 months. The traditional Chinese medicine syndrome score was performed before and after treatment, and the levels of proline peptidase (PLD), type Ⅳ collagen (Ⅳ-C) and type Ⅰ procollagen aminopeptidase (PINP) were detected by phthalaldehyde contrast colorimetry, and the levels of pentamylin 3 (PTX3), protein kinase B (Akt) and B cell activating factor receptor (BAFF-R) were determined by ELISA. Adverse events were recorded and clinical efficacy was evaluated.Results:The total effective rate in the observation group was 92.73% (51/55), while that in the control group was 76.36% (42/55), the difference between the two groups was statistically significant ( χ2=5.64, P=0.018). After treatment, the score and total score of costal pain and fullness, swelling and firmness, anorexia, white and greasy tongue coating in the observation group were significantly lower than those in the control group ( t values were 11.02, 7.36, 7.47, 6.38, 9.37, respectively, P<0.01). After treatment, the levels of serum PLD[(143.28±16.38)U/L vs. (160.69±18.35)U/L, t=5.25], Ⅳ-C[(71.93±8.33)μg/L vs. (83.12±9.91)μg/L, t=6.41], and PINP[(32.36±5.32)ng/L vs. (39.02±5.61)ng/L, t=6.39] in the observation group were significantly lower than those in the control group ( P<0.01); The levels of PTX3[(36.82±4.96)ng/L vs. (42.14±5.83)ng/L, t=5.15], Akt[(69.22±7.94)ng/L vs. (77.24±8.63)ng/L, t=5.07], and BAFF-R[(15.29±3.64)ng/L vs. (19.92±4.15)ng/L, t=6.22] in the observation group were significantly lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse reactions was 12.73% (7/55) in the observation group and 9.09% (5/55) in the control group, with no statistically significant difference between the two groups ( χ2=0.37, P=0.541). Conclusion:Qinggan Huashi Huoxue Decoction combined with conventional Western medicine therapy can improve the Traditional Chinese Medicine syndrome and the degree of liver fibrosis damage in patients with alcoholic cirrhosis with spleen deficiency and phlegm stasis syndrome, inhibit the expression of serum inflammatory factors, and improve clinical efficacy.

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