Hubungan antara Ekspresi AEG-1 dan MMP-9 pada Triple Negative Breast Cancer Operable dengan Disease Free Survival

Fernando Silalahi, dr. Kunta Setiaji Sp.B(K)Onk,; Prof. Dr. dr. Teguh Aryandono Sp.B(K)Onk;, dr. Paranita Ferronika, PhD.,Sp.PA(K)

2024 | Tesis-Subspesialis | SUBSPESIALIS ILMU BEDAH

Latar belakang: Kanker payudara menempati peringkat pertama sebagai jenis kanker yang terdiagnosis di Indonesia. Kanker payudara triple negative atau triple negative breast cancer (TNBC) memiliki perilaku biologi sangat invasif, gradasi dan indeks mitosis yang tinggi, agresif serta prognosis yang buruk. Astrocyte elevated gene-1 (AEG-1) adalah onkogen yang berperan penting pada proliferasi dan angiogenesis TNBC. MMP-9 berperan sebagai parameter invasi yang memainkan peran penting dalam remodeling matriks ekstraseluler dengan mendegradasi matriks ekstraseluler, yang meningkatkan pertumbuhan tumor payudara, invasi, metastasis, angiogenesis, dan proliferasi. Oleh karena itu AEG-1 dan MMP-9 berpotensi dapat digunakan sebagai penentuan prognosis pada TNBC operable

Tujuan: Menganalisis hubungan antara ekspresi AEG-1 dengan DFS, hubungan antara ekspresi MMP-9 dengan DFS, dan hubungan antara ekspresi AEG-1 dan MMP-9 pada Triple Negatif         Breast Cancer Operable 

Subjek dan Metode: Penelitian cohort ini melibatkan 54 sampel pasien kanker payudara subtipe TNBC Operable. Dilakukan pemeriksaan qRT-PCR untuk menilai ekspresi AEG-1 kemudian dikategorikan menjadi ekspresi rendah (low) dan tinggi (high) berdasarkan cut off optimal. Analisis univariat dan multivariat dalam penelitian ini menggunakan uji Cox regression untuk melihat variabel independen mana yang hubungannya lebih erat dengan variabel dependen. Analisis bivariat dengan menggunakan uji Chi-Square. Metode                 Kaplan-Meier dan log-rank digunakan untuk menilai survival analysis.

Hasil: Sampel penelitian sejumlah 54 pasien TNBC Operable. Median survival pasien dengan ekspresi AEG-1 tinggi adalah 9 bulan dan seluruh pasien adalah 31 bulan, ekspresi MMP-9 tinggi adalah 12 bulan dan seluruh pasien adalah 31 bulan. Terdapat hubungan yang signifikan antara ekspresi AEG-1 dengan DFS (p=0,000), antara MMP-9 dengan DFS (p=0,011). Ekspresi AEG-1 merupakan variabel paling berpengaruh terhadap DFS pada Cox Regression multivariat (p = 0,001 dan HR 5,363).

Kesimpulan: There was a significant relationship between AEG-1 expression and DFS, MMP-9 expression and DFS and AEG-1 expression and MMP-9 in operable TNBC patients.

Background: Breast cancer ranks first as a type of cancer diagnosed in Indonesia. Triple negative breast cancer (TNBC) has a highly invasive biological behavior, high mitotic grade and index, aggressive and poor prognosis. Astrocyte elevated gene-1 (AEG-1) is an oncogene that plays an important role in the proliferation and angiogenesis of TNBC. MMP-9 acts as an invasion parameter that plays an important role in extracellular matrix remodeling by degrading the extracellular matrix, which increases breast tumor growth, invasion, metastasis, angiogenesis, and proliferation. Therefore, AEG-1 and MMP-9 have the potential to be used as prognostic determinants in operable TNBC.

Purpose: Analyzing the relationship between AEG-1 expression and DFS, the relationship between MMP-9 expression and DFS, and the relationship between AEG-1 and MMP-9 expression in Operable Triple Negative Breast Cancer
Subjects and Methods: This cohort study involved 54 samples of TNBC Operable breast cancer patients. qRT-PCR examination was performed to assess AEG-1 expression and then categorized into low and high expression based on the optimal cut off. Univariate and multivariate analysis in this study used the Cox regression test to see which independent variables were more closely related to the dependent variable. Bivariate analysis used the Chi-Square test. The Kaplan-Meier and log-rank methods were used to assess survival analysis.

Results: The study sample consisted of 54 Operable TNBC patients. The median survival of patients with high AEG-1 expression was 9 months and all patients were 31 months, high MMP-9 expression was 12 months and all patients were 31 months. There was a significant relationship between AEG-1 expression and DFS (p = 0.000), between MMP-9 and DFS (p = 0.011). AEG-1 expression was the most influential variable on DFS in multivariate Cox Regression (p = 0.001 and HR 5.363).

Conclusion: There was a significant association between AEG-1 and MMP-9, AEG-1 and DFS, MMP-9 and DFS.

Kata Kunci : AEG-1, MMP-9, TNBC, DFS