Evaluation of Nuclear Factor of Activated T-cells (NFATc1) Expression in Non-metastatic Osteosarcoma Tissue

Evaluation of NFATc1 in Osteosarcoma
Vol. 21 No. 2 : 2026 (697-710)

Syurahbil Abdul Halim Syurahbil Abdul Halim
Jufithri Abd Halim Jufithri Abd Halim
Sahran Yahya Sahran Yahya
Wan Faisham Numan Wan Ismail Wan Faisham Numan Wan Ismail
Sharifah Emilia Tuan Sharif Sharifah Emilia Tuan Sharif
Muhamad Syahrul Fitri Zawawi Muhamad Syahrul Fitri Zawawi

Abstract
Osteosarcoma, a primary malignant bone tumour, poses significant challenges in treatment and prognosis despite advancements in therapy. The expression of nuclear factor of activated T cells c1 (NFATc1) in osteosarcoma tissue remains underexplored as a potential therapeutic target. This study aimed to evaluate NFATc1 protein expression in human non-metastatic osteosarcoma tissue samples and its correlation with patient survival and its subtypes. Secondarily, we examined the association between clinico-demographic details and survival of osteosarcoma patients. A cross-sectional study was conducted on 31 patients with primary non-metastatic osteosarcoma. Immunohistochemical analysis was used to assess NFATc1 protein expression in surgically resected tissue specimens. Demographic data, treatment details and follow-up records were collected for analysis. The study population had a mean age of 20.0 years, with Malay ethnicity being predominant. NFATc1 protein expression was positive in 25.8% of cases predominantly in conventional osteosarcoma (30.4%). No significant correlation was found between NFATc1 protein expression and patient survival (p = 0.685) or osteosarcoma subtypes (p = 0.642). NFATc1-positive patients had lower odds of long-term survival compared to NFATc1-negative patients (OR = 0.550; 95% CI: 0.106 - 2.860), although this association was not statistically significant (p = 0.477). Among the clinico-demographic characteristics, only the type of surgery (limb salvage vs. amputation) showed a statistically significant association with survival (p = 0.002), while age, race, gender, site, pathological fracture, chemotherapy and surgery for recurrence did not. Therefore, NFATc1 alone does not appear to be a useful prognostic biomarker in non-metastatic osteosarcoma. Further study is recommended to explore NFATc1 in larger cohort of both non-metastatic and metastatic osteosarcoma.
Keywords : Immunohistochemistry; NFATc1; osteosarcoma; prognosis; survival,
Abstrak
Osteosarkoma, sejenis tumor tulang yang bersifat malignan, merupakan cabaran besar dalam rawatan dan prognosis walaupun terdapat kemajuan dalam terapi. Ekspresi faktor nuklear sel T diaktifkan c1 (NFATc1) dalam tisu osteosarkoma masih kurang diterokai sebagai sasaran terapeutik yang berpotensi. Kajian ini bertujuan untuk menilai ekspresi protein NFATc1 dalam sampel tisu osteosarkoma non-metastatik manusia serta hubung kaitnya dengan kelangsungan hidup pesakit dan subjenisnya. Kedua, kami mengenalpasti hubungan antara butiran demografi klinikal dan kelangsungan hidup pesakit osteosarkoma. Satu kajian keratan rentas telah dijalankan ke atas 31 pesakit osteosarkoma non-metastatik primer. Analisis imunohistokimia digunakan untuk menilai ekspresi protein NFATc1 dalam spesimen tisu yang dikeluarkan secara pembedahan. Data demografi, butiran rawatan dan rekod susulan telah dikumpulkan untuk analisis. Populasi kajian mempunyai purata umur 20.0 tahun, didominasi oleh etnik Melayu. Ekspresi protein NFATc1 adalah positif dalam 25.8%, terutamanya dalam osteosarkoma konvensional (30.4%). Tiada korelasi yang signifikan ditemui antara ekspresi protein NFATc1 dengan kelangsungan hidup pesakit (p = 0.685) atau subjenis osteosarcoma (p = 0. 642). Pesakit dengan NFATc1 positif mempunyai kebarangkalian yang lebih rendah untuk kelangsungan hidup jangka panjang berbanding pesakit NFATc1-negatif (OR = 0.550; 95% CI: 0.106 - 2.860), walaupun perkaitan ini tidak signifikan secara statistik (p = 0.477). Dalam kalangan ciri-ciri klinik-demografi yang dikaji, hanya jenis pembedahan (penyelamatan anggota badan vs. amputasi) menunjukkan perkaitan yang signifikan secara statistik dengan kelangsungan hidup (p = 0.002), manakala umur, bangsa, jantina, tapak, patah patologi, kemoterapi,= dan pembedahan untuk berulang tidak menunjukkan perkaitan yang signifikan. Protein NFATc1 semata-mata tidak berupaya menjadi faktor prognostik dalam osteosarkoma non-metastatik. Kajian lanjut disarankan untuk menerokai NFATc1 dalam kohort yang lebih besar bagi kedua-dua osteosarkoma non-metastatik dan metastatik.
Kata Kunci : Immunohistokimia; kemandirian; NFATc1; osteosarkoma; prognosis,

Correspondance Address
*Correspondence: msf.zawawi@usm.my


Positive NFATc1 from a 16-year-old boy with osteoblastic osteosarcoma distal femur. After the surgical resection, he underwent 6 courses chemotherapy with 95% necrosis. NFATc1 was found to be positive as shown, and he survived 10 years disease free (NFATc1: Nuclear factor of activated T cells c1)