HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy
Abstract Background Lymph node metastasis is one of the pivotal factors of the clinical outcomes of patients with esophageal cancer receiving neoadjuvant chemoradiation therapy (NACRT). Both the nuclear factor‐erythroid 2‐related factor 2 (Nrf2) signaling pathway and heme oxygenase‐1 (HO‐1) are freq...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-03-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1477 |
| _version_ | 1818755612217966592 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ryujiro Akaishi |
| collection | DOAJ |
| description | Abstract Background Lymph node metastasis is one of the pivotal factors of the clinical outcomes of patients with esophageal cancer receiving neoadjuvant chemoradiation therapy (NACRT). Both the nuclear factor‐erythroid 2‐related factor 2 (Nrf2) signaling pathway and heme oxygenase‐1 (HO‐1) are frequently upregulated in various human malignancies and associated with resistance to chemoradiation therapy, subsequently resulting in adverse clinical outcomes. However, the Nrf2 and HO‐1 status in lymph node metastasis and their differences between primary and metastatic lesions are unknown. Aims To examine the levels of Nrf2 signaling proteins and HO‐1 in primary and metastatic lesions of patients with esophageal squamous cell carcinoma using immunohistochemistry. Methods and Results We immunolocalized Nrf2 signaling proteins in 69 patients with lymph node metastases, who received NACRT with 5‐fluorouracil and cisplatin before esophagectomy. We also compared the findings between primary and metastatic lesions. Residual lymph node metastases were detected in 30 patients and among them, both primary and metastatic lesions were available for evaluation in 25 patients. Subsequently, we correlated the results with patients' survival. Nrf2, HO‐1, and the Ki‐67 labeling index were all significantly lower in the patients with lymph node metastases than in those with primary tumors. Carcinoma cells with high HO‐1 levels were significantly associated with pathological resistance to NACRT. These results suggested that overall and disease‐free survival of esophageal squamous cell carcinoma were significantly associated with both pN2 and high HO‐1 levels, respectively. Conclusions Protein expression in the Nrf2 pathway was significantly lower in patients with lymph node metastases than in those with primary lesions. HO‐1 levels in lymph node metastases could be used to predict the eventual clinical outcome of patients with esophageal cancer receiving NACRT. |
| first_indexed | 2024-12-18T05:41:55Z |
| format | Article |
| id | doaj.art-f661bb26d96b40c6bb52d16f95ba68a2 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-12-18T05:41:55Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-f661bb26d96b40c6bb52d16f95ba68a22022-12-21T21:19:10ZengWileyCancer Reports2573-83482022-03-0153n/an/a10.1002/cnr2.1477HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapyRyujiro Akaishi0Fumiyoshi Fujishima1Hirotaka Ishida2Junichi Tsunokake3Takuro Yamauchi4Yusuke Gokon5Shunsuke Ueki6Toshiaki Fukutomi7Hiroshi Okamoto8Kai Takaya9Chiaki Sato10Yusuke Taniyama11Tomohiro Nakamura12Naoki Nakaya13Takashi Kamei14Hironobu Sasano15Department of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Pathology Tohoku University Hospital Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Health Record Informatics Information Security Tohoku Medical Megabank Organization, Tohoku University Sendai JapanDepartment of Health and Social Services Saitama Prefectural University Graduate School Koshigaya JapanDepartment of Surgery Tohoku University Graduate School of Medicine Sendai JapanDepartment of Pathology Tohoku University Hospital Sendai JapanAbstract Background Lymph node metastasis is one of the pivotal factors of the clinical outcomes of patients with esophageal cancer receiving neoadjuvant chemoradiation therapy (NACRT). Both the nuclear factor‐erythroid 2‐related factor 2 (Nrf2) signaling pathway and heme oxygenase‐1 (HO‐1) are frequently upregulated in various human malignancies and associated with resistance to chemoradiation therapy, subsequently resulting in adverse clinical outcomes. However, the Nrf2 and HO‐1 status in lymph node metastasis and their differences between primary and metastatic lesions are unknown. Aims To examine the levels of Nrf2 signaling proteins and HO‐1 in primary and metastatic lesions of patients with esophageal squamous cell carcinoma using immunohistochemistry. Methods and Results We immunolocalized Nrf2 signaling proteins in 69 patients with lymph node metastases, who received NACRT with 5‐fluorouracil and cisplatin before esophagectomy. We also compared the findings between primary and metastatic lesions. Residual lymph node metastases were detected in 30 patients and among them, both primary and metastatic lesions were available for evaluation in 25 patients. Subsequently, we correlated the results with patients' survival. Nrf2, HO‐1, and the Ki‐67 labeling index were all significantly lower in the patients with lymph node metastases than in those with primary tumors. Carcinoma cells with high HO‐1 levels were significantly associated with pathological resistance to NACRT. These results suggested that overall and disease‐free survival of esophageal squamous cell carcinoma were significantly associated with both pN2 and high HO‐1 levels, respectively. Conclusions Protein expression in the Nrf2 pathway was significantly lower in patients with lymph node metastases than in those with primary lesions. HO‐1 levels in lymph node metastases could be used to predict the eventual clinical outcome of patients with esophageal cancer receiving NACRT.https://doi.org/10.1002/cnr2.1477chemotherapymetastasespathologyradiation therapy |
| spellingShingle | 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 HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy Cancer Reports chemotherapy metastases pathology radiation therapy |
| title | HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| title_full | HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| title_fullStr | HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| title_full_unstemmed | HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| title_short | HO‐1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| title_sort | ho 1 in lymph node metastasis predicted overall survival in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation therapy |
| topic | chemotherapy metastases pathology radiation therapy |
| url | https://doi.org/10.1002/cnr2.1477 |
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