E‐cadherin is a robust prognostic biomarker in colorectal cancer and low expression is associated with sensitivity to inhibitors of topoisomerase, aurora, and HSP90 in preclinical models

Bruun, Jarle; Eide, Peter W.; Bergsland, Christian H.; Brück, Oscar; Svindland, Aud; Arjama, Mariliina; Välimäki, Katja; Bjørnslett, Merete; Guren, Marianne G.; Kallioniemi, Olli; Nesbakken, Arild; Lothe, Ragnhild A.; Pellinen, Teijo

doi:10.1002/1878-0261.13159

Cited by 7 publications

(9 citation statements)

References 71 publications

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“…Our assessment showed that E-cadherin levels were significantly reduced after NACT, confirming the usefulness of E-cadherin as a predictive marker for NACT. This result is consistent with previous studies in BC 39 , 40 , but it is in contrast to results obtained in colorectal cancer where E-cadherin is inversely associated with tumor stage 41 .…”

Section: Discussionsupporting

confidence: 92%

Neoadjuvant chemotherapy reduces the levels of HMGB1 and E-cadherin in patients with breast cancer

Su,

Wang,

Zhu

et al. 2023

Sci Rep

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This study investigated the changes in serum tumor marker levels in patients with breast cancer (BC) after neoadjuvant chemotherapy (NACT) and their potential as prognostic factors in NACT. A total of 134 consecutive patients with BC treated at our hospital between January 2019 and December 2021 were retrospectively analyzed. Patients were treated with NACT based on the docetaxel, epirubicin, and cyclophosphamide (TEC) regimen and assessed for marker levels, T cell subsets, and therapeutic outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the markers. Outcome assessments showed that NACT effectively reduced the tumor size, leading to increased complete remission, partial remission, stable disease, and significantly reduced disease progression. Improved immune function has also been observed after NACT. The levels of two (E-cadherin and HMGB1) out of five markers (CA153, CK19, CEA, E-cadherin, and HMGB1) were significantly reduced after NACT before surgery compared with those at admission, suggesting that NACT modulates the levels of biomarkers. ROC analysis revealed that the area under the curve (AUC) of HMGB1 and E-cadherin combination was 0.87 for discrimination of therapeutic response with a sensitivity and specificity of 91.3% and 88.4%, respectively. Serum tumor marker levels were reduced after NACT in patients with BC. The reduction was most prominent for HMGB1, followed by E-cadherin. These biomarkers can be used to predict the therapeutic response to NACT with an AUC of 0.87, thus offering a new tool to monitor treatment progress in NACT for patients with BC.

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Section: Discussionsupporting

confidence: 92%

Neoadjuvant chemotherapy reduces the levels of HMGB1 and E-cadherin in patients with breast cancer

Su,

Wang,

Zhu

et al. 2023

Sci Rep

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“…These values were used for the first time for patient grouping. E-cadherin status can impact the response to certain treatments (30,31). For instance, in hormone receptorpositive breast cancers, E-cadherin expression may influence the response to endocrine therapies such as tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker

KAO,

CHEN,

CHU

et al. 2024

In Vivo

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Background/Aim: Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. Materials and Methods: Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. Results: Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the Ecadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. Conclusion:Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.Breast-conserving surgery (BCS), also known as lumpectomy or partial mastectomy, aims to excise a tumor or a section of the breast while preserving as much healthy tissue as possible (1, 2). Despite its benefits, BCS may carry a slightly higher risk of local recurrence compared to mastectomy, particularly when the tumor is large or margins 1143

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“…If more than 20% of cancer cells exhibited positive staining in the cytoplasm or nucleus, it was categorized as aberrant expression. Aberrant expression was characterized by the absence of membranous staining and the presence of ectopic expression in the cytoplasm or nucleus [ 8 , 9 ].…”

Section: Methodsmentioning

confidence: 99%

Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer

Hussein,

Hassawi,

Ibraheem

2024

Cureus

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Background Colorectal cancer (CRC) is a significant global health challenge with high mortality rates. Dysregulation of β-catenin, epithelial-mesenchymal transition (EMT), and adenomatous polyposis coli (APC) are crucial in CRC development. Mutations in the APC gene lead to aberrant β-catenin expression, a key player in CRC pathogenesis. β-catenin not only influences canonical Wnt signaling but also regulates EMT. This study investigated the correlation between APC mutations, β-catenin dysregulation, and EMT induction in CRC. Methodology Tissue samples from 96 CRC patients and 40 para-cancerous normal tissues were collected and subjected to immunohistochemistry to assess β-catenin, E-cadherin, ZEB1, Snail, and vimentin expression. Genomic DNA was extracted and analyzed for APC mutations. Next-generation sequencing was employed for data analysis. Results Aberrant β-catenin expression was found in 82.3% of CRC cases and correlated with advanced clinicopathological factors. Aberrant β-catenin expression was associated with age (p=0.01), tumor invasion depth (p=0.03), nodal/distant metastasis (p=0.001 and 0.004), and vascular invasion (p=0.001). Aberrant β-catenin was correlated with EMT status. A positive correlation was observed between aberrant β-catenin expression and ZEB1 (p=0.001), Snail (p=0.001), vimentin (p=0.001), and loss of membranous E-cadherin (p=0001). Coexistence of aberrant β-catenin and EMT markers was associated with advanced CRC progression. Cancerous tissues displayed higher aberrant β-catenin and EMT markers expression than para-cancerous tissues. APC mutations were present in 59.3% of cases, with 91.2% of mutated APC cases showing aberrant β-catenin expression. The coexistence of APC mutation and aberrant β-catenin expression was correlated with the clinical outcomes of CRC patients. Mutated APC cases exhibited significantly increased EMT marker expression. Conclusion This study underscores the importance of aberrant β-catenin expression in CRC progression, linked to APC mutations and EMT induction. Understanding these relationships could aid in developing targeted therapies for CRC.

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E‐cadherin is a robust prognostic biomarker in colorectal cancer and low expression is associated with sensitivity to inhibitors of topoisomerase, aurora, and HSP90 in preclinical models

Cited by 7 publications

References 71 publications

Neoadjuvant chemotherapy reduces the levels of HMGB1 and E-cadherin in patients with breast cancer

Neoadjuvant chemotherapy reduces the levels of HMGB1 and E-cadherin in patients with breast cancer

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker

Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer

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