Sains Malaysiana 52(1)(2023): 187-197

http://doi.org/10.17576/jsm-2023-5201-15

Immunophenotyping of Gastritis, Gastric Ulcer and Gastric Cancer using a Cluster of Differentiation (CD) Antibody Microarray

(Imunofenotip Gastritis, Ulser Gaster dan Kanser Gaster menggunakan Mikroarai Antibodi Kelompok Pembezaan (CD))

ALFIZAH HANAFIAH^1,*, ASIF SUKRI², NIK RITZA KOSAI³, MOHAMAD AZNAN SHUHAILI³, MUSTAFA MOHAMMED TAHER³ & RAJA AFFENDI RAJA ALI⁴

¹Department of Medical Microbiology & Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

²Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam, 42300 Selangor Darul Ehsan, Malaysia

³Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

⁴Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 23 September 2021/Diterima: 11 Oktober 2022

Abstract

One of the factors that contribute to the development of gastric cancer is the host immune response. Extensive immunophenotype of gastric cancer can be identified by using antibody microarray technique that profiles more than 100 cluster of differentiation (CD) antigens in parallel. In this study, we used DotScan^TM antibody microarray to profile CD antigen expression in patients with distinct digestive diseases for surface antigen disease-signatures. Patients’ blood samples with gastric disorders and healthy controls were taken and processed for leukocytes isolation using Histopaque density gradient centrifugation. Leukocytes were captured onto DotScan^TM slides and cell binding densities were analyzed using DotReader^TM. Different groups of gastric diseases were found to be characterized by differentially expressed distinct CD antigens. Compared to normal healthy controls, 17, two and four highly expressed CD antigens were identified in gastritis, gastric ulcer and gastric cancer patients, respectively. The 17 CD antigens that show differential expression in gastritis were CD15, CD16, CD20, CD23, CD24, CD25, CD28, CD34, CD37, CD77, CD102, CD103, CD122, CD128, CD10, CD183, and CD184.  High expression of CD64 and CD69 were found in gastric ulcer, whereas CD52, CD126, CD135, and CD121a were highly expressed in gastric cancer. CD antigens involve in T-cell functions had reduced expression in gastric cancer, while proinflammatory cytokines shows increased expression. These results demonstrate specific immunophenotype of CD antigens in patients with various gastric diseases and identification of differential expressed surface antigens may have clinical significance for diagnostic and therapeutic purposes.

Keywords: Cluster of differentiation antigen; gastric cancer; gastric ulcer; gastritis; immunophenotype

ABSTRAK

Salah satu faktor yang menyumbang kepada perkembangan kanser perut adalah tindak balas imun perumah. Pengenalpastian imunofenotip kanser perut yang meluas dapat dilakukan dengan menggunakan teknik mikroarai antibodi yang memaparkan lebih daripada 100 kelompok antigen pembezaan (CD) secara serentak. Dalam kajian ini, mikroarai antibodi DotScan^TM digunakan untuk memprofil pengekspresan antigen CD pada pesakit dengan penyakit pencernaan untuk mengenal pasti penanda antigen permukaan pada pelbagai jenis penyakit pencernaan. Sampel darah pesakit dengan penyakit gaster dan individu kawalan sihat diambil dan diproses untuk pengasingan leukosit menggunakan kaedah emparan kecerunan Histopaque.  Leukosit ditangkap ke atas slaid DotScan^TM dan kepadatan pengikatan antigen dan antibodi dianalisis menggunakan DotReader^TM. Keputusan kajian ini menunjukkan kumpulan penyakit gaster yang berlainan dapat dicirikan oleh ekspresi kelompok antigen CD yang berbeza. Berbanding dengan kawalan normal yang sihat, 17, dua dan empat antigen CD yang diekspres secara berbeza dikenal pasti masing-masing pada pesakit gastritis, ulser gaster dan kanser perut.  17 antigen CD yang menunjukkan perbezaan ekspresi dalam gastritis adalah CD15, CD16, CD20, CD23, CD24, CD25, CD28, CD34, CD37, CD77, CD102, CD103, CD122, CD128, CD10, CD183 dan CD184. Ekspresi CD64 dan CD69 yang tinggi didapati pada penyakit ulser gaster, manakala ekspresi yang tinggi CD52, CD126, CD135 dan CD121a dilihat pada penyakit kanser perut. Antigen CD yang terlibat dalam fungsi sel-T mengalami penurunan ekspresi pada kanser perut, manakala sitokin proinflamasi menunjukkan peningkatan ekspresi. Hasil kajian ini menunjukkan imunofenotip antigen CD adalah khusus pada pesakit dengan pelbagai penyakit gaster dan pengenalpastian antigen permukaan yang diekspres secara berbeza mungkin mempunyai kepentingan klinikal bagi tujuan diagnostik dan rawatan penyakit.

Kata kunci: Gastritis; imunofenotip; kanser perut; kelompok antigen pembezaan; ulser gaster

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