Association between tumor necrosis factor receptor 2 and progression and poor prognosis of tumor stage 2‑3 esophageal squamous cell carcinoma and stratified analysis

Liu,Zifeng; Ren,Mei; Jia,Shasha; Qiao,Sen; Yang,Dong

doi:10.3892/ol.2024.14638

Association between tumor necrosis factor receptor 2 and progression and poor prognosis of tumor stage 2‑3 esophageal squamous cell carcinoma and stratified analysis

Authors:
- Zifeng Liu
- Mei Ren
- Shasha Jia
- Sen Qiao
- Dong Yang
View Affiliations

Affiliations: Department of Oncology, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Department of Oncology, Jining No. 1 People's Hospital, Jining, Shandong 272029, P.R. China, Department of Hepatological Surgery, Jining No. 1 People's Hospital, Jining, Shandong 272029, P.R. China, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
Published online on: August 21, 2024 https://doi.org/10.3892/ol.2024.14638
Article Number: 505
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Although tumor necrosis factor receptor 2 (TNFR2) may serve a protumor role in several types of tumors, the clinical significance of TNFR2, including the diagnostic and prognostic value in tumor (T) stage 2‑3 esophageal squamous cell carcinoma (ESCC), remains unclear. Therefore, the present study aimed to explore the clinical significance of TNFR2 in stage T2‑3 ESCC. The present study collected the mRNA expression data of TNFR2 from two databases and confirmed the high expression of TNFR2 in ESCC tissue. TNFR2 expression in stage T2‑3 ESCC tissue (n=404) was detected using immunohistochemistry and a stratified analysis was performed. For all patients with stage T2‑3 ESCC, TNFR2 expression was associated with clinical stage, invasion depth and metastatic lymph nodes. Stage T3 and low differentiation was associated with an increase in the risk of lymph node metastasis, but older age was associated with a decrease. TNFR2 expression was associated with poor overall survival (OS) of all patients with stage T2‑3 ESCC and stratified patients with stage T3 ESCC. Moreover, TNFR2 expression and metastatic lymph nodes were independent prognostic factors for these patients. For stratified patients aged ≤60 years, TNFR2 expression was associated with clinical stage and metastatic lymph nodes. In addition, TNFR2 expression was associated with poor OS in stratified patients with stage T2 ESCC. The presence of metastatic lymph nodes was also an independent prognostic factor for these patients. For stratified patients aged >60 years, TNFR2 expression was associated with invasion depth. TNFR2 expression was also associated with poor OS in all patients with stage T2‑3 ESCC and stratified patients with stage T3 ESCC. TNFR2 expression and metastatic lymph nodes were identified as independent prognostic factors for these patients. In conclusion, TNFR2 expression is associated with progression and poor prognosis in patients with stage T2‑3 ESCC as an independent prognostic factor, except in the subgroup of patients with stage T2‑3 ESCC aged ≤60 years.

View Figures

View References

1	Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, Ferlay J and Arnold M: The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology. 163:649–658.e2. 2022. View Article : Google Scholar : PubMed/NCBI
2	Codipilly DC and Wang KK: Squamous cell carcinoma of the esophagus. Gastroenterol Clin North Am. 51:457–484. 2022. View Article : Google Scholar : PubMed/NCBI
3	Voron T, Julio C and Pardo E: Esophageal carcinoma: Novelties and challenges in surgery. Bull Cancer. 110:533–539. 2023. View Article : Google Scholar : PubMed/NCBI
4	Xu J, Kato K, Raymond E, Hubner RA, Shu Y, Pan Y, Park RS, Ping L, Jiang Y, Zhang J, et al: Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): A global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 24:483–495. 2023. View Article : Google Scholar : PubMed/NCBI
5	Waters JK and Reznik SI: Update on management of squamous cell esophageal cancer. Curr Oncol Rep. 24:375–385. 2022. View Article : Google Scholar : PubMed/NCBI
6	Edge SB and Compton CC: The American joint committee on cancer: The 7^th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
7	Wang J, Wu N, Zheng QF, Yan S, Lv C, Li SL and Yang Y: Evaluation of the 7^th edition of the TNM classification in patients with resected esophageal squamous cell carcinoma. World J Gastroenterol. 20:18397–18403. 2014. View Article : Google Scholar : PubMed/NCBI
8	Mensink M, Tran TNM, Zaal EA, Schrama E, Berkers CR, Borst J and Kivit SD: TNFR2 costimulation differentially impacts regulatory and conventional CD4(+) T-Cell Metabolism. Front Immunol. 13:8811662022. View Article : Google Scholar : PubMed/NCBI
9	Babic A, Shah SM, Song M, Wu K, Meyerhardt JA, Ogino S, Yuan C, Giovannucci EL, Chan AT, Stampfer MJ, et al: Soluble tumour necrosis factor receptor type II and survival in colorectal cancer. Br J Cancer. 114:995–1002. 2016. View Article : Google Scholar : PubMed/NCBI
10	Torrey H, Butterworth J, Mera T, Okubo Y, Wang L, Baum D, Defusco A, Plager S, Warden S, Huang D, et al: Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Sci Signal. 10:2017. View Article : Google Scholar : PubMed/NCBI
11	Wei MX, Song X, Zhao XK, Han WL, Bao Q, Han XN, Xu RH, Li XM, Fan ZM, Wang R, et al: Clinicopathological characteristics and postoperative prognosis of patients with nuclear pedigree of esophageal squamous cell carcinoma. Front Oncol. 13:11904572023. View Article : Google Scholar : PubMed/NCBI
12	Zhang H and Xiao W: TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes. Cell Biol Int. 41:415–422. 2017. View Article : Google Scholar : PubMed/NCBI
13	Bai J, Ding B and Li H: Targeting TNFR2 in Cancer: All roads lead to rome. Front Immunol. 13:8449312022. View Article : Google Scholar : PubMed/NCBI
14	He T, Zhao Y, Zhao P, Zhao L, Zakaria J and Wang K: Signaling pathway(s) of TNFR2 required for the immunoregulatory effect of CD4(+)Foxp3(+) regulatory T cells. Int Immunopharmacol. 108:1088232022. View Article : Google Scholar : PubMed/NCBI
15	Gao Z, Zhang Q, Chen H, Chen J, Kang J, Yu H, Song Y and Zhang X: TNFR2 promotes pancreatic cancer proliferation, migration, and invasion via the NF-κB signaling pathway. Aging. 15:8013–8025. 2023. View Article : Google Scholar : PubMed/NCBI
16	Wang L, Yang D, Tian J, Gao A, Shen Y, Ren X, Li X, Jiang G and Dong T: Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer. Oncotarget. 8:26323–26333. 2017. View Article : Google Scholar : PubMed/NCBI
17	Qu Y, Wang X, Bai S, Niu L, Zhao G, Yao Y, Li B and Li H: The effects of TNF-α/TNFR2 in regulatory T cells on the microenvironment and progression of gastric cancer. Int J Cancer. 150:1373–1391. 2022. View Article : Google Scholar : PubMed/NCBI
18	Kashyap A, Rapsomaniki MA, Barros V, Fomitcheva-Khartchenko A, Martinelli AL, Rodriguez AF, Gabrani M, Rosen-Zvi M and Kaigala G: Quantification of tumor heterogeneity: From data acquisition to metric generation. Trends Biotechnol. 40:647–676. 2022. View Article : Google Scholar : PubMed/NCBI
19	Patel SS, Nelson R, Sanchez J, Lee W, Uyeno L, Garcia-Aguilar J, Hurria A and Kim J: Elderly patients with colon cancer have unique tumor characteristics and poor survival. Cancer. 119:739–7347. 2013. View Article : Google Scholar : PubMed/NCBI
20	Lin Y, Ye Y, Huang Q, Zheng B, Yang Y, Chen Y, Li W, Ke H, Lin C, Zhang Y, et al: Influence of age as a continuous variable on survival outcomes and treatment options in patients with upper thoracic esophageal carcinoma. J Cancer. 14:1039–1048. 2023. View Article : Google Scholar : PubMed/NCBI
21	Zhang P, Wang S, Wu JZ and Song Q: Clinical and prognostic significance of perioperative change in red cell distribution width in patients with esophageal squamous cell carcinoma. BMC Cancer. 23:3192023. View Article : Google Scholar : PubMed/NCBI
22	Feng RB, Zhou QZ, Cheng R, Li P, Zhu ST, Min L and Zhang ST: Expression and significance of N-myc downstream regulated gene 2 in the process of esophageal squamous cell carcinogenesis. Bioengineered. 13:3275–3283. 2022. View Article : Google Scholar : PubMed/NCBI
23	Luo QY, Di T, Qiu MZ, Xia ZF, Du Y, Lin RD, Yang LQ, Sun YT, Yang DJ, Sun J and Zhang L: High AKAP8L expression predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Cell Int. 22:902022. View Article : Google Scholar : PubMed/NCBI
24	Xie C, Chen Z, Xu J, Meng Z, Huang Z and Lin J: Influence of lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): A single-center retrospective study. Peer J. 10:e129742022. View Article : Google Scholar : PubMed/NCBI
25	Wang N, Li Y, Zhou RM, Wang GY, Wang CM, Chen ZF and Liu W: Hsa-miR-196a2 functional SNP is associated with the risk of ESCC in individuals under 60 years old. Biomarkers. 19:43–48. 2014. View Article : Google Scholar : PubMed/NCBI
26	Silva Raju J, Abd Aziz NH, Atallah GA, Teik CK, Shafiee MN, Mohd Saleh MF, Jeganathan R, Md Zin RR and Kampan NC: Prognostic value of TNFR2 and STAT3 among high-grade serous ovarian cancer survivors according to platinum sensitivity. Diagnostics (Basel). 11:5262021. View Article : Google Scholar : PubMed/NCBI
27	Zhang YW, Chen QQ, Cao J, Xu LQ, Tang X, Wang J, Zhang J and Dong LX: Expression of tumor necrosis factor receptor 2 in human non-small cell lung cancer and its role as a potential prognostic biomarker. Thoracic Cancer. 10:437–444. 2019. View Article : Google Scholar : PubMed/NCBI