TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer
BackgroundToll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) signaling play a critical role in colorectal cancer (CRC) development. Despite extensive research, the relationship between genetic variations and protein expression patterns during adenoma-carcinoma progression rema...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1568729/full |
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| author | Thai Tra Dang Thai Tra Dang Viet Nhat Pham Ngoc Dung Tran Thu Hang Ngo Van Mao Can Huy Hoang Nguyen Thi Xuan Nguyen Thanh Chung Dang |
| author_facet | Thai Tra Dang Thai Tra Dang Viet Nhat Pham Ngoc Dung Tran Thu Hang Ngo Van Mao Can Huy Hoang Nguyen Thi Xuan Nguyen Thanh Chung Dang |
| author_sort | Thai Tra Dang |
| collection | DOAJ |
| description | BackgroundToll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) signaling play a critical role in colorectal cancer (CRC) development. Despite extensive research, the relationship between genetic variations and protein expression patterns during adenoma-carcinoma progression remains poorly understood.MethodsWe conducted a cross-sectional study of 176 CRC patients and 131 adenoma patients. Inclusion criteria required histologically confirmed primary colorectal tumors with adequate tissue content (≥30% tumor cells). TLR4 and MyD88 protein expression was evaluated using immunohistochemistry with standardized scoring systems. DNA sequencing identified genetic variants in TLR4 and MyD88 genes. Multivariate analyses assessed associations between protein expression, genetic variants, and clinicopathological features.ResultsTLR4 expression was significantly higher in CRC compared to adenomas (66.5% vs 30.5%, p<0.001), with MyD88 showing widespread expression in both groups (CRC: 97.2%, adenoma: 95.4%). We identified novel variants in TLR4 (9:117713042) and MyD88 (rs138284536), significantly associated with increased CRC risk (OR=8.92, 95% CI: 1.14-69.95, p=0.037 and OR=20.01, 95% CI: 4.72-84.83, p<0.001, respectively). The MyD88 variant correlated with aggressive features including mucinous histology (43.5% vs 22.7%, p=0.036), advanced pT stage (29.6% vs 13.2%, p=0.044), and perineural invasion (61.5% vs 22.1%, p=0.004). Combined TLR4/MyD88 scores ≥5 significantly predicted lymph node metastasis (42.9% vs 28.3%, p=0.046) and high-grade tumor budding (p=0.002).ConclusionsOur study identifies distinct TLR4/MyD88 expression patterns in CRC progression and novel genetic variants associated with aggressive tumor features. These molecular alterations may serve as potential biomarkers for risk stratification and prognostic assessment in CRC patients, while offering promising targets for therapeutic intervention. |
| format | Article |
| id | doaj-art-15ee64bef92e4b2cb7fc25f5d6af636f |
| institution | Matheson Library |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-15ee64bef92e4b2cb7fc25f5d6af636f2025-07-09T04:12:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15687291568729TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancerThai Tra Dang0Thai Tra Dang1Viet Nhat Pham2Ngoc Dung Tran3Thu Hang Ngo4Van Mao Can5Huy Hoang Nguyen6Thi Xuan Nguyen7Thanh Chung Dang8Department of Pathology and Forensic Medicine, Military Hospital 103, Vietnam Military Medical University, Hanoi, VietnamDepartment of Pathophysiology, Vietnam Military Medical University, Hanoi, VietnamInstitute of Biology, Vietnam Academy of Science and Technology, Hanoi, VietnamDepartment of Pathology and Forensic Medicine, Military Hospital 103, Vietnam Military Medical University, Hanoi, VietnamDepartment of Pathophysiology, Vietnam Military Medical University, Hanoi, VietnamDepartment of Pathophysiology, Vietnam Military Medical University, Hanoi, VietnamInstitute of Biology, Vietnam Academy of Science and Technology, Hanoi, VietnamInstitute of Biology, Vietnam Academy of Science and Technology, Hanoi, VietnamDepartment of Pathology and Forensic Medicine, Military Hospital 103, Vietnam Military Medical University, Hanoi, VietnamBackgroundToll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) signaling play a critical role in colorectal cancer (CRC) development. Despite extensive research, the relationship between genetic variations and protein expression patterns during adenoma-carcinoma progression remains poorly understood.MethodsWe conducted a cross-sectional study of 176 CRC patients and 131 adenoma patients. Inclusion criteria required histologically confirmed primary colorectal tumors with adequate tissue content (≥30% tumor cells). TLR4 and MyD88 protein expression was evaluated using immunohistochemistry with standardized scoring systems. DNA sequencing identified genetic variants in TLR4 and MyD88 genes. Multivariate analyses assessed associations between protein expression, genetic variants, and clinicopathological features.ResultsTLR4 expression was significantly higher in CRC compared to adenomas (66.5% vs 30.5%, p<0.001), with MyD88 showing widespread expression in both groups (CRC: 97.2%, adenoma: 95.4%). We identified novel variants in TLR4 (9:117713042) and MyD88 (rs138284536), significantly associated with increased CRC risk (OR=8.92, 95% CI: 1.14-69.95, p=0.037 and OR=20.01, 95% CI: 4.72-84.83, p<0.001, respectively). The MyD88 variant correlated with aggressive features including mucinous histology (43.5% vs 22.7%, p=0.036), advanced pT stage (29.6% vs 13.2%, p=0.044), and perineural invasion (61.5% vs 22.1%, p=0.004). Combined TLR4/MyD88 scores ≥5 significantly predicted lymph node metastasis (42.9% vs 28.3%, p=0.046) and high-grade tumor budding (p=0.002).ConclusionsOur study identifies distinct TLR4/MyD88 expression patterns in CRC progression and novel genetic variants associated with aggressive tumor features. These molecular alterations may serve as potential biomarkers for risk stratification and prognostic assessment in CRC patients, while offering promising targets for therapeutic intervention.https://www.frontiersin.org/articles/10.3389/fonc.2025.1568729/fullTLR4/MyD88 pathwaycolorectal carcinogenesisgenetic polymorphismsmolecular biomarkersclinicopathological featuresmicrosatellite instability |
| spellingShingle | Thai Tra Dang Thai Tra Dang Viet Nhat Pham Ngoc Dung Tran Thu Hang Ngo Van Mao Can Huy Hoang Nguyen Thi Xuan Nguyen Thanh Chung Dang TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer Frontiers in Oncology TLR4/MyD88 pathway colorectal carcinogenesis genetic polymorphisms molecular biomarkers clinicopathological features microsatellite instability |
| title | TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer |
| title_full | TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer |
| title_fullStr | TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer |
| title_full_unstemmed | TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer |
| title_short | TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer |
| title_sort | tlr4 myd88 expression patterns and novel genetic variants association with aggressive clinicopathological features in colorectal cancer |
| topic | TLR4/MyD88 pathway colorectal carcinogenesis genetic polymorphisms molecular biomarkers clinicopathological features microsatellite instability |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1568729/full |
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