Sains Malaysiana 53(10)(2024): 3253-3262

http://doi.org/10.17576/jsm-2024-5310-02

Perbandingan Pengekspresan Antigen Kluster Pembezaan dalam Subjenis Tumor dan Darah Periferi Pesakit Kanser Gaster

(Comparison of Cluster of Differentiation Antigens Expression in Tumor Subtypes and Peripheral Blood of Gastric Cancer Patients)

ASIF SUKRI¹, ALFIZAH HANAFIAH^2,*, NIK RITZA KOSSAI³, MOHAMAD AZNAN SHUHAILI³, MUSTAFA MOHAMMED TAHER³ & RAJA AFFENDI RAJA ALI⁴

¹Jabatan Sains Biologi dan Bioteknologi, Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

²Jabatan Mikrobiologi Perubatan dan Imunologi, Fakulti Perubatan, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia

³Jabatan Surgeri, Fakulti Perubatan, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia

⁴Sekolah Perubatan dan Sains Kesihatan, Sunway University Bandar Sunway, 47500 Petaling Jaya, Selangor, Malaysia

Diserahkan: 30 April 2024/Diterima: 10 Julai 2024

Abstrak

Kanser gaster merupakan salah satu kanser utama yang paling banyak menyebabkan kematian di seluruh dunia. Diagnosis dan prognosis kanser gaster adalah sukar untuk dibuat dan kebanyakan pesakit didiagnos dengan kanser ini pada peringkat yang teruk. Prognosis kanser gaster adalah berlainan berdasarkan kepada subjenis kanser gaster dan jangkitan Helicobacter pylori. Antigen kluster pembezaan (CD) boleh digunakan sebagai biopenanda untuk diagnosis dan prognosis penyakit kronik kerana pengekspresannya yang berubah mengikut tahap penyakit. Objektif kajian ini adalahuntuk membuat perbandingan pengekspresan antigen CD dalam sel darah periferi dan sel adenokarsinoma pesakit kanser gaster dan menentukan peranan CD55 dalam rembesan interleukin-8 (IL-8) oleh sel selanjar. Sampel darah periferi dan tumor telah diambil daripada pesakit kanser gaster. Sampel kemudian diproses untuk mendapatkan ampaian sel tunggal. Imunofenotip antigen CD telah dijalankan menggunakan slaid mikroatur DotScan^TM. Penyenyapan CD55 telah dibuat menggunakan RNA pengganggu kecil (siRNA). Sembilan belas antigen CD, kebanyakan daripadanya adalah penanda untuk sel B, diekspres secara lebih tinggi dalam tumor subjenis kardia berbanding subjenis bukan kardia. CD182 dan CD125 merupakan reseptor interleukin yang penting, diekspres lebih tinggi dalam subjenis bukan kardia daripada subjenis kardia. Pengekspresan 32 antigen CD yang lebih tinggi dapat diperhatikan dalam tumor subjenis difus berbanding subjenis usus. CD29 dan CD73 diekspres dengan tinggi dalam sarkoma gastrointestinal. Perbandingan pengekspresan antigen CD menunjukkan CD11a dan CD49d diekspres sama tinggi dalam darah dan tumor. Penyenyapan CD55 mengawal pengeluaran IL-8 dalam sel yang dijangkiti oleh H. pylori secara bergantung kepada kehadiran gen berkaitan sitotoksin (cagA). Kajian ini menunjukkan perbezaan pengekspresan antigen CD dalam pelbagai subjenis kanser gaster dan berpotensi dijadikan biopenanda untuk diagnosis kanser gaster secara tidak invasif.

Kata kunci: CD55; Helicobacter pylori; kanser gaster; kluster pembezaan  Top of Form

Abstract

Gastric cancer is one of the major cancers that cause the most deaths worldwide. Diagnosis and prognosis of gastric cancer are difficult to make, and most patients are diagnosed with this cancer at an advanced stage. The prognosis of gastric cancer varies depending on the subtype of gastric cancer and the infection of Helicobacter pylori. Cluster of differentiation (CD) antigens can be used as biomarkers for the diagnosis and prognosis of chronic diseases because their expression changes according to the disease stage. The objective of this study was to compare the expression of CD antigens in peripheral blood cells and adenocarcinoma cells of gastric cancer patients and to determine the role of CD55 in the secretion of interleukin-8 (IL-8) in gastric epithelial cells. Peripheral blood and tumor samples were collected from gastric cancer patients. The samples were then processed to obtain single-cell suspensions. Immunophenotyping of CD antigens was performed using DotScan^TM microarray slides. CD55 silencing was performed using small interfering RNA (siRNA). Nineteen CD antigens, most of which are markers for B cells, were expressed higher in cardia than non-cardia subtypes. CD182 and CD125, important interleukin receptors, were expressed higher in non-cardia than cardia subtypes. Higher expression of 32 CD antigens was observed in diffuse subtypes compared to intestinal subtypes. CD29 and CD73 were highly expressed in gastrointestinal sarcoma. Comparison of CD antigen expression showed CD11a and CD49d expressed equally high in blood and tumor. CD55 knockdown regulated IL-8 secretion in cells infected by H. pylori in a cytotoxin-associated gene (cagA)-dependent manner. This study demonstrates differences in CD antigen expression in various subtypes of gastric cancer and the potential for them to be used as non-invasive biomarkers for gastric cancer diagnosis.

Keywords: CD55;Top of Form cluster of differentiation; gastric cancer; Helicobacter pylori

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*Pengarang untuk surat-menyurat; email: alfizah@ppukm.ukm.edu.my