Citation: | GUAN Shoutao, WANG Dengzheng, HU Fengchao, NING Linlin, AN Yue, GENG Hui, WANG Yuqiang. Expression levels of FOXO1 and SMAD4 in esophageal cancer tissues and their relationships with clinicopathological features and prognosis[J]. Journal of Clinical Medicine in Practice, 2024, 28(17): 9-14. DOI: 10.7619/jcmp.20240996 |
To investigate the expression levels of FOXO1 and SMAD4 in esophageal cancer (EC) tissues and their associations with clinicopathological features and prognosis.
Tissue samples of cancerous and adjacent non-cancerous tissues were collected from 131 EC patients. Hematoxylin-eosin (HE) staining was performed to observe the pathological morphology of EC and adjacent tissues. The mRNA expression of FOXO1 and SMAD4 was measured using quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of FOXO1 and SMAD4 was determined by immunohistochemistry; Spearman's correlation analysis was employed to assess the correlation between FOXO1 and SMAD4 protein expression in EC tissues; Cox regression analysis was conducted to analyze factors influencing the prognosis of EC patients; Kaplan-Meier analysis was used to perform survival analysis for EC patients.
The expression of FOXO1 mRNA and its protein positive expression rate were significantly higher in the EC tissues than those in the adjacent tissues, whereas the expression of SMAD4 mRNA and its protein positive expression rate were significantly lower (P < 0.05). FOXO1 and SMAD4 were associated with tumor diameter, tumor differentiation, lymph node metastasis and TNM stage (P < 0.05). A negative correlation was observed between FOXO1 and SMAD4 protein expression in EC tissues (r=-0.419, P < 0.05). FOXO1, SMAD4, tumor diameter, differentiation, lymph node metastasis and TNM stage were identified as factors influencing mortality in EC patients (P < 0.05). The 3-year overall survival rate of EC patients was 84.73% (111/131). The 3-year cumulative survival rate was significantly lower in the EC patients with positive FOXO1 expression than in thosewith negative FOXO1 expression (P < 0.05), while it was significantly higher in patients with positive SMAD4 expression than in those with negative SMAD4 expression (P < 0.05).
The positive expression rate of FOXO1 is higher, while that of SMAD4 is lower in EC tissues. Their protein expressions were associated with clinicopathological features and prognosis in EC patients. FOXO1 and SMAD4 may serve as important biomarkers for predicting the prognosis of EC.
[1] |
HARADA K, ROGERS J E, IWATSUKI M, et al. Recent advances in treating oesophageal cancer[J]. F1000Res, 2020, 9: F1000FacultyRev-F1000Faculty1189.
|
[2] |
WATANABE M, OTAKE R, KOZUKI R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer[J]. Surg Today, 2020, 50(1): 12-20. doi: 10.1007/s00595-019-01878-7
|
[3] |
姜哲, 韩佳慧, 吴婷, 等. 环状RNA_0005273对食管癌细胞生物学行为的影响及可能机制[J]. 实用临床医药杂志, 2023, 27(9): 46-52. doi: 10.7619/jcmp.20230533
|
[4] |
DAI C, RENNHACK J P, ARNOFF T E, et al. SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization[J]. Cell Rep, 2021, 36(4): 109443. doi: 10.1016/j.celrep.2021.109443
|
[5] |
PAKRAVAN K, RAZMARA E, MAHMUD HUSSEN B, et al. SMAD4 contributes to chondrocyte and osteocyte development[J]. J Cell Mol Med, 2022, 26(1): 1-15.
|
[6] |
XU X L, ZHENG L, HANG N, et al. The transcription factor c-Jun regulates Smad4 expression by upregulating pre-miR-183 expression to promote invasion and metastasis of esophageal squamous cell carcinomas[J]. In Vitro Cell Dev Biol Anim, 2020, 56(7): 550-558. doi: 10.1007/s11626-020-00499-6
|
[7] |
CHEN H, ZHENG B, XUE S T, et al. Knockdown of miR-183 enhances the cisplatin-induced apoptosis in esophageal cancer through increase of FOXO1 expression[J]. Onco Targets Ther, 2020, 13: 8463-8474. doi: 10.2147/OTT.S258680
|
[8] |
赵锡江. 食管癌诊断与治疗[M]. 天津: 天津科技翻译出版公司, 1999: 90-106.
|
[9] |
吴蓓, 高春辉, 陶连元, 等. FoxO1蛋白在原发性肝癌(PHC)组织中的表达及与对预后的影响[J]. 实用癌症杂志, 2021, 36(6): 899-902.
|
[10] |
WANG Z C, CHEN M L, QIU Y B, et al. Identification of potential biomarkers associated with immune infiltration in the esophageal carcinoma tumor microenvironment[J]. Biosci Rep, 2021, 41(2): BSR20202439. doi: 10.1042/BSR20202439
|
[11] |
JIANG Z D, WANG J, SHEN Z Y, et al. Characterization of esophageal microbiota in patients with esophagitis and esophageal squamous cell carcinoma[J]. Front Cell Infect Microbiol, 2021, 11: 774330. doi: 10.3389/fcimb.2021.774330
|
[12] |
郑浩, 张仁泉. 浅谈早期食管癌的微创治疗[J]. 临床外科杂志, 2021, 29(8): 711-713.
|
[13] |
PENG S M, LI W, HOU N N, et al. A review of FoxO1-regulated metabolic diseases and related drug discoveries[J]. Cells, 2020, 9(1): 184.
|
[14] |
陈洁, 耿慧武, 王凤杰, 等. FoxO1蛋白在癌细胞质中的差异表达及其功能研究[J]. 安徽医科大学学报, 2021, 56(12): 1847-1852.
|
[15] |
GRUPP K, UZUNOGLU F G, MELLING N, et al. FOXO1 overexpression and loss of pSerine256-FOXO1 expression predicts clinical outcome in esophageal adenocarcinomas[J]. Sci Rep, 2018, 8(1): 17370.
|
[16] |
WANG Y, LYU Z J, QIN Y R, et al. FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma[J]. Theranostics, 2020, 10(25): 11535-11548.
|
[17] |
XIONG W J, HE W Z, WANG T T, et al. Smad4 deficiency promotes pancreatic cancer immunogenicity by activating the cancer-autonomous DNA-sensing signaling axis[J]. Adv Sci, 2022, 9(7): e2103029.
|
[18] |
LI J, HAN X, GU Y, et al. LncRNA MTX2-6 suppresses cell proliferation by acting as ceRNA of miR-574-5p to accumulate SMAD4 in esophageal squamous cell carcinoma[J]. Front Cell Dev Biol, 2021, 9: 654746.
|
[19] |
XU R, ZHOU X M, LI Y S, et al. MicroRNA-181a promotes epithelial-mesenchymal transition in esophageal squamous cellcarcinoma via the TGF-β/Smad pathway[J]. Mol Med Rep, 2021, 23(5): 316.
|
[20] |
YAO W, WANG S Q, DU X, et al. SMAD4 inhibits granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis[J]. Reprod Sci, 2022, 29(5): 1577-1585.
|