TY - JOUR
T1 - Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma
AU - Akaishi, Ryujiro
AU - Fujishima, Fumiyoshi
AU - Ishida, Hirotaka
AU - Tsunokake, Junichi
AU - Yamauchi, Takuro
AU - Gokon, Yusuke
AU - Ueki, Shunsuke
AU - Fukutomi, Toshiaki
AU - Okamoto, Hiroshi
AU - Takaya, Kai
AU - Sato, Chiaki
AU - Taniyama, Yusuke
AU - Nakamura, Tomohiro
AU - Nakaya, Naoki
AU - Kamei, Takashi
AU - Sasano, Hironobu
N1 - Funding Information:
RA and FF performed immunohistochemistry. RA, FF, HI, TN, and NN performed the statistical analyses. RA, FF, HI, JT, TY, YG, SU, TF, HO, KT, CS, YT, TN, NN, TK, and HS, conceived the study, participated in its design and coordination, and helped draft the manuscript. All authors have read and approved the final manuscript. We appreciate the technical assistance provided by Ms. Yayoi Aoyama (Department of Pathology, Tohoku University Hospital, Sendai, Japan). We would like to thank Editage (www.editage.com ) for English language editing.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - Chemoradiotherapy
KW - Esophageal squamous cell carcinoma
KW - Heme oxygenase-1
KW - Neoadjuvant therapy
KW - Thioredoxin reductase 1
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U2 - 10.1007/s10388-021-00904-3
DO - 10.1007/s10388-021-00904-3
M3 - Article
C2 - 34999996
AN - SCOPUS:85122583778
SN - 1612-9059
VL - 19
SP - 436
EP - 443
JO - Esophagus
JF - Esophagus
IS - 3
ER -