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Comprehensive analysis of gene expression alterations in breast cancer patients via PKCθ-TBK1-mTORC1 signaling
Amna Hafeez1, Mahnoor Basit1, Sameen Zafar1
1Department of Biomedicine, Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Sector H-12, Islamabad, 44000, Pakistan.
Background:
Breast cancer remains a leading cause of cancer-related mortality among women globally. The emergence of chemoresistance and the lack of early detection tools necessitate the identification of reliable molecular biomarkers and therapeutic targets. Protein kinase C theta (PRKCQ/PKCθ), a serine/threonine kinase, has been implicated in immune signaling and cancer. The current study was designed to investigate the relative expression levels of PRKCQ and its downstream components, including TANK-binding kinase 1 (TBK1), mammalian target of rapamycin (mTORC1), ribosomal S6 kinase (S6K), Jun Proto-Oncogene (JUNB), and the tumor suppressor gene p21, in breast cancer. The study also aimed to evaluate their association with key clinicopathological features.
Methods:
Gene expression analysis was conducted using quantitative real-time PCR (qRT-PCR) on breast cancer blood samples. Expression levels were compared between breast cancer patients and healthy controls, and further analyzed to metastasis, cancer stage, histological subtype, molecular classification, family history, BRCA status, menopausal status, and lactation history.
Results:
Expression of PRKCQ, TBK1, mTORC1, S6K, and JUNB was significantly upregulated in breast cancer blood samples compared to controls, whereas p21 expression was downregulated. Statistically significant associations were observed between gene expression levels and various clinicopathological parameters. Notably, PRKCQ showed strong differential expression across molecular subtypes with the highest expression in TNBC. A signaling axis involving PRKCQ-TBK1-mTORC1-S6K and an independent PRKCQ-JUNB-VEGFR axis was proposed.
Conclusion:
The relative expression of PRKCQ and its associated signaling components suggests their critical role in breast cancer progression. These molecules, especially PRKCQ, may serve as potential biomarkers for early detection and prognosis, as well as targets for therapeutic intervention following further validation.
Insights
Protein kinase C theta (PRKCQ) and related genes are upregulated in breast cancer, suggesting their potential as early detection biomarkers. Downregulated p21 indicates a role in cancer progression, highlighting PRKCQ as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer is a leading cause of mortality in women.
- Chemoresistance and lack of early detection necessitate new biomarkers and therapeutic targets.
- Protein kinase C theta (PRKCQ) is implicated in immune signaling and cancer.
Purpose of the Study:
- Investigate PRKCQ and downstream component expression in breast cancer.
- Analyze associations between gene expression and clinicopathological features.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) on breast cancer blood samples.
- Compared gene expression in patients versus healthy controls.
- Analyzed expression relative to metastasis, stage, subtype, and BRCA status.
Main Results:
- PRKCQ, TBK1, mTORC1, S6K, and JUNB were upregulated; p21 was downregulated in breast cancer patients.
- Significant associations found between gene expression and clinicopathological parameters.
- PRKCQ showed differential expression across subtypes, highest in TNBC; proposed PRKCQ-TBK1-mTORC1-S6K and PRKCQ-JUNB-VEGFR axes.
Conclusions:
- PRKCQ and associated signaling components play a role in breast cancer progression.
- PRKCQ may serve as a biomarker for early detection and prognosis.
- PRKCQ represents a potential therapeutic target for breast cancer.
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