Phân tích tổng hợp gene p16INK4α (Cyclin Dependent Kinase Inhibitor 2A) - Một trong những yếu tố dẫn đến bệnh ung thư vòm họng=Meta-analysis: p16INK4α (Cyclin Dependent Kinase Inhibitor 2A) is one of the major causes of nasopharyngeal cancer

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Tác giả: Hiếu Nguyễn Trung, Huệ Thiều Hồng, Phạm Thị Thúy Ngọc, Nguyễn Thị Ngọc Thảo, Thư Trần Bích, Thuận Lao Đức, Lê Huyền Ái Thuý

Ngôn ngữ: vie

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Thông tin xuất bản: Tạp chí khoa học Đại học Mở Thành phố Hồ Chí Minh - Kỹ thuật và Công nghệ, 2024

Mô tả vật lý: tr.2025-03-12

Bộ sưu tập: Metadata

ID: 252028

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Nasopharyngeal carcinoma (NPC) is a rare type of tumor originating from the region behind the nasal cavity and above the throat. The primary causes of NPC include Epstein-Barr virus infection, genetic mutations, and environmental factors, such as lifestyle. Global and Vietnamese studies have indicated enhanced methylation in the promoter region of CpG islands, contributing to the development of various cancers, including NPC (Chan, Teo, & Johnson, 2002). The p16INK4α gene, also known as cyclin-dependent kinase inhibitor, is a tumor suppressor gene that inhibits Cyclin-Dependent Kinase (CDK), leading to the inhibition of CDK interaction with cyclin, thereby inhibiting the phosphorylation process on pRb, halting the cell cycle. The p16INK4α gene is located on the short arm of chromosome 9 at position 9p21.3, consisting of three exons encoding 156 amino acids (Coppé et al., 2011). According to a meta-analysis of 11 papers on methylation processes on the p16 INK4α gene conducted by Xiao et al. in 2016, significantly higher levels of methylation were found in NPC tissue samples compared to non-tumor samples (Xiao et al., 2016). Additionally, methylation on the p16INK4α gene in blood samples from NPC patients was also significantly higher compared to normal blood samples. Therefore, this article aims to provide further scientific evidence on the enhanced methylation status in the promoter region of CpG islands of NPC patients based on the analysis of the p16INK4α gene using statistical synthesis methods. The research results demonstrated an uneven expression frequency of the p16INK4α gene between the two patient groups and the control group. In the patient group, we observed a Q value of 104.5223 with degrees of freedom (DF) = 13 and a p-value <
0.0001, along with an I2 index of 87.56%, with a 95% confidence interval for I2 from 80.84 to 91.9. Meanwhile, in the control group, the Q value was 56.1888 (p <
0.001), and the I2 index reached 76.86%, with a 95% confidence interval for I2 from 61.38 to 86.14. The weighted frequency of the patient and control groups was 63.478% and 7.966%, respectively, indicating a significant difference between the patient and control groups, with a high Q value and a very low p-value. Other factors that may influence the methylation process, such as ethnicity and sample source, were also included in the analysis. The results showed a significant correlation between the methylation process in these two groups and the development of NPC. Specifically, the Odds Ratios (OR) for China and Africa were 7.002 and 6.47, respectively. We also observed that the OR for samples from the mucosa and body fluids were 6.802 and 5.516, respectively. The analysis confirmed that the expression of the p16INK4α gene is strongly related to the formation of throat cancer. Therefore, this data provides a foundation for experimental studies on NPC samples collected from the Vietnamese population.Ung Thư Vòm Họng (UTVH) là một loại khối u hiếm xuất phát từ khu vực phía sau khoang mũi và phía trên của hầu. Các nguyên nhân chính của UTVH bao gồm: nhiễm Virus Epstein-Barr, sự biến đổi gen và do yếu tố môi trường, lối sống. Nghiên cứu trên toàn cầu và tại Việt Nam đã chỉ ra sự tăng cường methyl hóa trên vùng promoter của các đảo CpG, góp phần vào sự hình thành của nhiều loại ung thư, trong đó có UTVH (Chan, Teo, & Johnson, 2002). Gene p16INK4α còn được gọi là cyclin-dependent kinase inhibitor, là một gene ức chế khối u, có vai trò ức chế Cyclin-Dependent Kinase (CDK), dẫn đến việc CDK không tương tác với cyclin, từ đó ức chế quá trình phosphoryl trên pRb, làm ngưng chu trình tế bào. Gene p16INK4α nằm trên phần ngắn của nhiễm sắc thể số 9 vị trí 9p21.3 bao gồm ba exon mã hóa 156 axit amin (Coppé & ctg., 2011). Theo một nghiên cứu tổng hợp từ 11 bài báo về quá trình methyl hóa trên gene p16INK4α, tiến hành bởi Xiao, Jiang, Hu, và Liào năm 2016 đã cho thấy sự tồn tại của quá trình methyl hóa vượt mức trong mẫu khối u vòm họng cao hơn đáng kể so với mẫu không có khối u (Xiao & ctg., 2016). Ngoài ra, sự methyl hóa trên gene p16INK4α trong mẫu máu của bệnh nhân UTVH cũng cao hơn đáng kể so với mẫu máu bình thường. Vì thế, bài báo này nhằm cung cấp thêm dữ liệu có tính khoa học về tình trạng tăng cường methyl hóa trong vùng promoter trên đảo CpG của bệnh nhân mắc UTVH dựa trên việc phân tích gene p16INK4α bằng phương pháp tổng hợp thống kê. Kết quả nghiên cứu cho thấy tần suất biểu hiện của gene p16INK4α không đồng đều giữa hai nhóm bệnh và nhóm chứng. Trong nhóm bệnh, chúng tôi quan sát thấy giá trị Q = 104.5223 với bậc tự do DF = 13 và giá trị p <
0.0001, cùng với chỉ số I2 là 87.56%, với khoảng tin cậy 95% cho chỉ số I2 từ 80.84 đến 91.9. Trong khi đó, trong nhóm chứng, giá trị Q là 56.1888 (p <
0.001), và chỉ số I2 đạt 76.86%, với khoảng tin cậy 95% cho chỉ số I2 từ 61.38 đến 86.14. Tần số có trọng số của nhóm bệnh và nhóm chứng tương ứng là 63.478% và 7.966%, cho thấy có sự khác biệt giữa nhóm bệnh và nhóm chứng, với giá trị Q cao và giá trị p rất nhỏ. Các yếu tố khác có thể ảnh hưởng đến quá trình methyl hóa, như dân tộc và nguồn mẫu, cũng được đưa vào phân tích. Kết quả cho thấy rằng quá trình methyl hóa trong hai nhóm này có mối tương quan đáng kể với sự phát triển của UTVH. Cụ thể, chỉ số OR tương đối cho Trung Quốc và Châu Phi lần lượt là 7.002 và 6.47. Chúng ta cũng quan sát được rằng chỉ số OR cho nhóm nguồn mẫu từ mô và dịch cơ thể lần lượt là 6.802 và 5.516. Phân tích kết quả đã xác nhận rằng sự biểu hiện của gene p16INK4α có mối liên quan mạnh đến quá trình hình thành khối u vòm họng. Vì vậy, dữ liệu này tạo nền tảng cho các nghiên cứu thực nghiệm trên mẫu UTVH thu thập từ người Việt Nam.

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