TROY is a promising prognostic biomarker in patients with colorectal cancer

Nishioka, Michio; Suehiro, Yutaka; Sakai, Kazuhisa; Matsumoto, Toshihiko; Okayama, Naoko; Mizuno, Hidekazu; Ueno, Koji; Suzuki, Nobuaki; Hashimoto, Shinichi; Takami, Taro; Hazama, Shoichi; Nagano, Hiroaki; Sakaida, Isao; Yamasaki, Takahiro

doi:10.3892/ol.2018.8079

Cited by 3 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This remark suggests that Lgr5 could be used in clinical practice as a potential prognostic factor. A similar conclusion of a high level of Lgr5 is an unfavorable factor with a shorter OS and disease-free survival (independent from tumor size) was also given in many other studies (Takahashi et al 2011;Wu et al 2012Wu et al , 2016Hsu et al 2013;Jiang et al 2015;Nishioka et al 2018). There are a couple (Walker et al 2011;Carmon et al 2017;Jang et al 2018;Leng et al 2018).…”

Section: Discussionsupporting

confidence: 79%

“…The recent works have emphasized that a high level of this CSC marker is positively correlated with regards to both tumor size and the depth of invasion into surrounding tissues. (Fan et al 2010 ; Hsu et al 2013 ; Jiang et al 2015 ; Nishioka et al 2018 ; Zheng et al 2018 ). Zhou et al observed in their study that patients with CRC had reduced Lgr5 expression in more advanced stages (Zhou et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

Gzil

Zarębska

Jaworski

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Introduction Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. Materials and methods The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. Results The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). Conclusion Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymphnode metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

Gzil

Zarębska

Jaworski

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…This remark suggests that LGR5 could be used in clinical practice as a potential prognostic factor. A similar conclusion of a high level of LGR5 is an unfavorable factor with a shorter OS and DFS was also given in several studies 29,37…”

Section: Discussionsupporting

confidence: 76%

“…A similar conclusion of a high level of LGR5 is an unfavorable factor with a shorter OS and DFS was also given in several studies. 29,37 However, certain reports have also demonstrated contrary results for the relation between LGR5 expression and the prognosis of CC. For example, Ziskin et al 38 noted that LGR5 expression was not significantly associated with the outcome of tumors.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer

Abdelrahman¹,

El-Azony

Elsebai

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

The potentiation and activation of Wnt signaling pathways are now assumed to mediate the self-renewal and proliferation of colon cancer stem cells that are responsible for therapeutic resistance, tumor relapse, and metastasis. We aimed to evaluate LGR5, Prox1, and Notch1 immunohistochemical expression in stage II to III colon cancer. Their predictive role of tumor relapse, overall survival, and disease-free survival was statistically analyzed. Our results revealed that high LGR5 expression was identified in 56.7% of the patients, LGR5 expression was significantly associated with left-sided tumors (P < 0.001). Moreover, its expression was significantly associated with the unfavorable tumor characteristics including high grade, deep invasion (pT), lymph node metastasis, and advanced tumor stage (P < 0.001 for each). High Prox1 expression was observed in 65% of the cases, and its expression was significantly associated with tumor grade, lymph node metastasis, and the advanced tumor stage (P = 0.004, 0.009, 0.016, respectively). Positive Notch1 expression was identified in 35% of patients, and it was inversely associated with high grade lymph node metastasis, deep invasion (pT), and advanced tumor stage (P < 0.001 for each). During the follow-up period, the tumor relapse was significantly associated with high LGR5, high Prox1, and negative Notch1 expression. Shorter overall survival and disease-free survival were significantly associated with high LGR5, high Prox1, and negative Notch1 expression. High LGR5, high Prox1, and negative Notch1 expression are unfavorable prognostic factors in colon cancer. Prox1 is a crucial regulator of Notch-independent LGR5+ stem cells that is mostly responsible for relapse and therapeutic resistance in stage II to III colon cancer.

show abstract

“…Dysregulation of TROY expression has also been reported for several other malignancies such as melanomas [ 24 ] , glioblastomas [ 25 ] , and squamous cell carcinomas [ 26 ] . Recent studies on the function of TROY in GI cancers have mostly focused on colorectal cancer [ 16 , 23 , 27 ] , in which the role of Wnt signalling differs from that of gastric tissue. Fafilek and colleagues [ 16 ] , having carried out chromatin co-percipitation and DNA microarray studies on various colorectal cancer cell lines, demonstrated the co-precipitation of TROY and LGR5.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Analysis of LGR5 and TROY Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend

Saberi

Piryaei

Mirabzadeh

et al. 2019

ibj

View full text Add to dashboard Cite

Background: Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Methods: Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. Results: TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infectedmouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Conclusion: Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.

show abstract

TROY is a promising prognostic biomarker in patients with colorectal cancer

Cited by 3 publications

References 25 publications

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

Prognostic Impact of LGR5, Prox1, and Notch1 Biomarkers in Stage II to III Colon Cancer

Immunohistochemical Analysis of LGR5 and TROY Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend

Contact Info

Product

Resources

About