Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma.

Abstract

BACKGROUND:

Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown.

METHODS:

Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed.

RESULTS:

Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival.

CONCLUSIONS:

The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.

• Authors: Ryujiro Akaishi, Fumiyoshi Fujishima, Hirotaka Ishida, Junichi Tsunokake, Takuro Yamauchi, Yusuke Gokon, Shunsuke Ueki, Toshiaki Fukutomi, Hiroshi Okamoto, Kai Takaya, Chiaki Sato, Yusuke Taniyama, Tomohiro Nakamura, Naoki Nakaya, Takashi Kamei, Hironobu Sasano
• Journal: Esophagus : official journal of the Japan Esophageal Society (Esophagus) Vol. 19 Issue 3 Pg. 436-443 (07 2022) ISSN: 1612-9067 [Electronic] Japan
• PMID: 34999996 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• NF-E2-Related Factor 2
• HMOX1 protein, human
• Heme Oxygenase-1
• TXNRD1 protein, human
• Thioredoxin Reductase 1

Topics

• Esophageal Neoplasms (drug therapy, radiotherapy)
• Esophageal Squamous Cell Carcinoma (drug therapy, pathology)
• Heme Oxygenase-1 (genetics, therapeutic use)
• Humans
• NF-E2-Related Factor 2 (therapeutic use)
• Neoadjuvant Therapy
• Thioredoxin Reductase 1 (genetics)