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The Best Way to Treat Nasopharyngeal Cancer is Through Identifying Gene Expression in Bone Metastases

Medical Science Doctoral Program student of the Faculty of Medical Science (FK) of Universitas Indonesia (UI), dr. Rahmat Cahyanur, SpPD, K-HOM, was declared to have passed his open doctoral promotion session owing to his research on the role of gene expression in the spread of nasopharyngeal cancer to the bone. This research was done due to the numerous cases of nasopharyngeal cancer found in Southeast Asia, especially in Indonesia, with it reaching 28.4% of cases among head and neck cancers. Moreover, in Indonesia, the death rate of nasopharyngeal cancer has become the second highest in Asia after China.

Nasopharyngeal cancer grows at the upper part of the throat, right at the back of the nose, in the mucosal tissue layer in the nasopharyngeal region. The cancer cells spread to other body parts through a metastatic process which is also the main reason for cancer-induced pain and death. Because of that, the metastatic profile of the primary bone of the nasopharyngeal cancer needs to be known based on demography, the location of metastases, and the radiological image. Other than that, the difference in gene expression of nasopharyngeal cancer with bone metastases, without bone metastases, and with other organ metastases also require scrutiny.

In this research, Dr. Rahmat involved 95 research subjects, mostly male, consisting of 64 patients with metastases and 31 patients without metastases. Out of all the patients with metastases, 73.4% of them experienced the spreading of cancer cells to their bones, namely the spine (70.2%), ribs/chest (57.4%), and hips (27.7%).

Dr. Rahmat made use of the NanoString technology to measure the difference in gene expression from the Messenger Ribonucleic Acid (mRNA) extracted from the paraffin block. Gene expression is a process of making use of the genetic information stored in the gene to synthesize gene-product compounds. These compounds are common proteins, but there are other functional RNA compounds with non-protein codes. 

Found from the analysis, the gene expression of C-X-C Chemokine Receptor Type 4 (CXCR4) increases on all subjects, followed by Interleukin 8/IL-8 (93.68%), Steroid Receptor Coactivator/SRC (92.63%), Secreted Phosphoprotein 1/OPN (72.10%), Receptor Activator of Nuclear Factor (NF) – κB/RANK (62.10%), and Bone Morphogenetic Protein 2/BMP2 (58.95%). Gene Parathyroid Hormone Like Hormone (PTHLH) and Receptor Activator of Nuclear Factor (NF)-B Ligand (RANKL) each show an increase in 17.95% and 4.21% subjects. Compared to the group without metastases, the group with metastases showed a decrease in gene IL-8, while gene CXCR4 increased further.

Other than gene expression, research shows cell communication pathways, such as Wingless/Integrated (WNT) and G Protein-Coupled Receptor (GPCR), which play an important role in the group with bone metastases. “Knowledge of these pathways allows clinicians to identify and give targeted therapy to the patients’ working pathways. Meanwhile, gene candidates associated with the incidence of primary bone metastases are used as markers in managing cases of advanced nasopharyngeal cancer,” said Dr. Rahmat, who is also a teaching staff at the Department of Internal Medicine of FKUI. 

The result of Dr. Rahmat’s research is written in the dissertation titled, “Metastasis Tulang Primer pada Kanker Nasofaring: Kajian terhadap Ekspresi Gen CXCR4, RANK, RANKL, BMP2, OPN, PTHLH, IL-8, dan SRC.” The Doctoral Promotion Session was held on July 1, 2024, at the IMERI FKUI Building Auditorium (3rd Floor), Salemba, Jakarta. The session was chaired by the Dean of FKUI, Prof. Dr. dr. Ari Fahrial Syam, SpPD, KGEH, MMB, with Prof. Dr. dr. Achmad Fauzi Kamal, Sp.OT, Subsp. Onk. Ort. R. as promoter; and Dr. dr. Cosphiadi Irawan, Sp.PD, Subsp. H.O.M(K) and dr. Marlinda Adham, Sp.THT-KL(K), Subsp.Onk(K), Ph.D as co-promoters. 

As for the examiner team, Prof. Dr. dr. Suhendro, Sp.PD, Subsp. P.T.I(K) acted as the head with Prof. dr. Muchtaruddin Mansyur, M.S., Sp.Ok, Ph.D; Dr. dr. Lisnawati, Sp.P.A, Subsp. S.P.(K), Subsp. Kv.R.M.(K); dr. Mardiah Suci Hardianti, Sp.PD, Subs.H.O.M.(K) as team members, and Ahmad Rusdan Handoyo Utomo, Ph.D., as a guest examiner from the Biomedical Science Program of Universitas YARSI.

The Dean of FKUI, Prof. Ari Fahrial gave his appreciation to Dr. Rahmat. “Congratulations to Dr. Rahmat who also helped to increase the number of doctoral graduates from FKUI. The process of compiling research and a dissertation is not an easy one as it is filled with challenges. Furthermore, the topic of this research involves multiple scientific fields, so the discussions that occurred were sure to be broad and deep. Genetic-level studies should be the most effective strategy when we talk about cancer and its spreading process. Therefore, we hope that the result of this research can continue to be followed up by future research and innovation,” he said.

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