Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer
Although a therapeutic response to neoadjuvant chemoradiotherapy (NACRT) is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/β-catenin signal is known to be crucial for the tumorigenesis of color...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Sprog: | English |
| Udgivet: |
MDPI AG
2023-01-01
|
| Serier: | Biomedicines |
| Fag: | |
| Online adgang: | https://www.mdpi.com/2227-9059/11/1/174 |
| _version_ | 1827628279809441792 |
|---|---|
| author | Shoji Miyako Takeru Matsuda Yu-ichiro Koma Takahiro Koide Ryuichiro Sawada Hiroshi Hasegawa Kimihiro Yamashita Hitoshi Harada Naoki Urakawa Hironobu Goto Shingo Kanaji Taro Oshikiri Yoshihiro Kakeji |
| author_facet | Shoji Miyako Takeru Matsuda Yu-ichiro Koma Takahiro Koide Ryuichiro Sawada Hiroshi Hasegawa Kimihiro Yamashita Hitoshi Harada Naoki Urakawa Hironobu Goto Shingo Kanaji Taro Oshikiri Yoshihiro Kakeji |
| author_sort | Shoji Miyako |
| collection | DOAJ |
| description | Although a therapeutic response to neoadjuvant chemoradiotherapy (NACRT) is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/β-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association of Wnt/β-catenin signal activation with a pathological response to NACRT. The immunohistochemical expression of nuclear and membranous β-catenin was analyzed in biopsy samples obtained from 60 patients with locally advanced rectal cancer who received curative surgery following NACRT. The association of Wnt/β-catenin signal activation with their clinical outcomes was investigated. Notably, the body mass index of these patients was significantly higher in the low nuclear β-catenin expression group. Moreover, patients in the high nuclear β-catenin expression group tended to have more advanced disease and a higher rate of positive vascular invasion than those in the low expression group. Furthermore, the rate of good histological responses was significantly higher in the low nuclear β-catenin expression group (72% vs. 37.1%, <i>p</i> < 0.01). Overall, relapse-free survival tended to be better in patients with low nuclear/high membranous β-catenin expression (<i>n</i> = 9) than in other individuals (<i>n</i> = 51) (<i>p</i> = 0.093 and <i>p</i> = 0.214, respectively). Activation of the Wnt/β-catenin signal pathway represented by nuclear β-catenin accumulation was significantly associated with a poor response to NACRT in patients with rectal cancer. Analysis of nuclear β-catenin accumulation before starting treatment might help predict the therapeutic response to NACRT. |
| first_indexed | 2024-03-09T13:29:27Z |
| format | Article |
| id | doaj.art-a6ec3c7ea22c4a288638eb13b64a34fc |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T13:29:27Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-a6ec3c7ea22c4a288638eb13b64a34fc2023-11-30T21:20:32ZengMDPI AGBiomedicines2227-90592023-01-0111117410.3390/biomedicines11010174Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal CancerShoji Miyako0Takeru Matsuda1Yu-ichiro Koma2Takahiro Koide3Ryuichiro Sawada4Hiroshi Hasegawa5Kimihiro Yamashita6Hitoshi Harada7Naoki Urakawa8Hironobu Goto9Shingo Kanaji10Taro Oshikiri11Yoshihiro Kakeji12Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Surgery, Sanda City Hospital, Sanda 669-1321, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanAlthough a therapeutic response to neoadjuvant chemoradiotherapy (NACRT) is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/β-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association of Wnt/β-catenin signal activation with a pathological response to NACRT. The immunohistochemical expression of nuclear and membranous β-catenin was analyzed in biopsy samples obtained from 60 patients with locally advanced rectal cancer who received curative surgery following NACRT. The association of Wnt/β-catenin signal activation with their clinical outcomes was investigated. Notably, the body mass index of these patients was significantly higher in the low nuclear β-catenin expression group. Moreover, patients in the high nuclear β-catenin expression group tended to have more advanced disease and a higher rate of positive vascular invasion than those in the low expression group. Furthermore, the rate of good histological responses was significantly higher in the low nuclear β-catenin expression group (72% vs. 37.1%, <i>p</i> < 0.01). Overall, relapse-free survival tended to be better in patients with low nuclear/high membranous β-catenin expression (<i>n</i> = 9) than in other individuals (<i>n</i> = 51) (<i>p</i> = 0.093 and <i>p</i> = 0.214, respectively). Activation of the Wnt/β-catenin signal pathway represented by nuclear β-catenin accumulation was significantly associated with a poor response to NACRT in patients with rectal cancer. Analysis of nuclear β-catenin accumulation before starting treatment might help predict the therapeutic response to NACRT.https://www.mdpi.com/2227-9059/11/1/174rectal cancerβ-cateninNACRT |
| spellingShingle | Shoji Miyako Takeru Matsuda Yu-ichiro Koma Takahiro Koide Ryuichiro Sawada Hiroshi Hasegawa Kimihiro Yamashita Hitoshi Harada Naoki Urakawa Hironobu Goto Shingo Kanaji Taro Oshikiri Yoshihiro Kakeji Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer Biomedicines rectal cancer β-catenin NACRT |
| title | Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer |
| title_full | Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer |
| title_fullStr | Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer |
| title_full_unstemmed | Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer |
| title_short | Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer |
| title_sort | significance of wnt β catenin signal activation for resistance to neoadjuvant chemoradiotherapy in rectal cancer |
| topic | rectal cancer β-catenin NACRT |
| url | https://www.mdpi.com/2227-9059/11/1/174 |
| work_keys_str_mv | AT shojimiyako significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT takerumatsuda significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT yuichirokoma significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT takahirokoide significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT ryuichirosawada significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT hiroshihasegawa significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT kimihiroyamashita significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT hitoshiharada significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT naokiurakawa significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT hironobugoto significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT shingokanaji significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT tarooshikiri significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer AT yoshihirokakeji significanceofwntbcateninsignalactivationforresistancetoneoadjuvantchemoradiotherapyinrectalcancer |