Trichohyalin (TCHH), which functions as hair transparent keratin or hair matrix protein acts as a structural protein predominantly located in the outermost skin layer and hair shafts. As part of the keratin family, it demonstrates strong structural stability which enables it to sustain hair and skin integrity and function. TCHH supports hair development and growth while performing a role in the skin barrier function. Trichohyalin expression correlates with multiple physiological and pathological conditions while also being linked to both skin diseases and hair disorders.
Research indicates that TCHH functions within certain biological processes including wound healing which positions it as a viable candidate for therapeutic targeting. New research findings indicate TCHH expression is abnormal in cancer patients primarily with gastric cancer (GC) which suggests it could function as a novel prognostic biomarker.
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Trichohyalin (TCHH)
Trichohyalin (TCHH) represents a structural protein abundant in glutamine which scientists first identified in hair follicles and keratinocytes and which connects mainly to keratin and skin barrier operations. Current research reveals abnormal TCHH expression in cancers particularly gastric cancer where it may act as a new prognostic biomarker.
Expression Changes of Trichohyalin (TCHH) in Gastric Cancer
Gene Expression Analysis
TCHH expression levels showed significant downregulation in gastric cancer tissues according to analyses of the TCGA database and the GEO database. The mRNA and protein levels of TCHH were found to be reduced in gastric cancer patients compared to normal tissues according to immunohistochemistry and qRT-PCR results. TCHH expression levels remained higher in patients with early gastric cancer during stage I and II. The expression of TCHH significantly decreased in advanced gastric cancer that reached stage III or IV.
Methylation Regulation Mechanism
The promoter region of the TCHH gene showed hypermethylation in gastric cancer tissues indicating potential epigenetic regulation. 5-Aza treatment of gastric cancer cells led to restored TCHH expression which confirmed inhibition of its transcription.
The Potential of Trichohyalin (TCHH): a Prognostic Biomarker
Research has shown that capillary hypoxia-inducible factor (TCHH) functions as a potential prognostic biomarker across multiple cancer types including gastric cancer. The level of TCHH expression appears to show a relationship with how cancer develops and spreads and affects patient survival rates. Research has demonstrated that TCHH contributes significantly to gastric cancer development through its involvement in cell proliferation, apoptosis regulation, and various molecular pathways. Multiple factors such as genetic makeup along with environmental and lifestyle components influence the complexity of gastric cancer. The research of biomarkers provides a means to advance early detection of gastric cancer while enabling personalized treatment strategies and improving prognostic assessments. As scientists develop a deeper understanding of TCHH's function in gastric cancer, they will be able to create new diagnostic and treatment approaches for clinical application in the future.
Poor Prognosis Results from Low Levels of TCHH Expression
Gastric cancer patients with low TCHH expression demonstrated significantly reduced overall survival (OS) according to Kaplan-Meier survival analysis. The reduced length of disease-free survival indicated that TCHH might influence tumor recurrence risk.
Prognostic Model Integration
Prediction accuracy for survival rates of gastric cancer patients improved through the integration of TCHH expression with clinical pathological features such as TNM stage, degree of differentiation, and lymph node metastasis.
Function of Trichohyalin (TCHH) in Gastric Cancer Progression
Tumor Suppressor Effect
When TCHH is overexpressed, gastric cancer cells experience substantial inhibition of their proliferation, migration, and invasion abilities (examples include AGS and MKN45). Gastric cancer cells showed greater growth and invasion abilities following TCHH knockdown. The mouse xenograft model revealed that mice with TCHH overexpression showed significant tumor growth inhibition.
Possible Molecular Mechanism
EMT (epithelial-mesenchymal transition) regulation, in gastric cancer cells with low TCHH expression, E-cadherin was downregulated, N-cadherin and Vimentin were upregulated, indicating that TCHH may promote the malignant progression of gastric cancer through EMT. TCHH may reduce the accumulation of β-catenin in the cell nucleus by inhibiting the Wnt/β-catenin pathway, thereby reducing cell proliferation and migration ability.
Trichohyalin (TCHH) as a Potential Therapeutic Target
The common methylation of the TCHH promoter in gastric cancer patients indicates that inhibitors such as 5-Aza may restore TCHH expression and inhibit tumor growth. Reduced TCHH levels appear to be linked with chemotherapy resistance in cancer patients which indicates that combining TCHH with standard chemotherapy drugs could be an effective treatment strategy in future therapies. Researchers studying gastric cancer have identified epidermal gene transcription factor as a significant potential therapeutic target.
The protein has crucial involvement in multiple biological activities which include cell proliferation as well as differentiation processes and programmed cell death. Research indicates that TCHH expression levels correlate with tumor occurrence and progression across various cancer types. The growth and metastasis of gastric cancer cells are influenced by TCHH through its control over cell signaling pathways together with its effects on the tumor microenvironment and immune system interactions. The expression of TCHH remains low in gastric cancer and its presence correlates with worse patient outcomes. The occurrence and development of gastric cancer could be linked to TCHH via its influence on EMT and Wnt/β-catenin pathways. The methylation level of TCHH represents a potential candidate for both diagnostic and prognostic biomarkers and offers a new avenue for therapeutic targeting.
References
- O'Keefe, E., et al. Trichohyalin: a structural protein of hair, tongue, nail, and epidermis. Journal of investigative dermatology. 1993, 101(1): S65-S71.
- Rothnagel, J., et al. Trichohyalin, an intermediate filament-associated protein of the hair follicle. The Journal of cell biology. 1986, 102(4): 1419-1429.
- Yu, F., et al. TCHH as a Novel Prognostic Biomarker for Patients with Gastric Cancer by Bioinformatics Analysis. Clinical and Experimental Gastroenterology. 2024: 61-74.
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