Disertasi

Peran MicroRNA-224 dan MicroRNA-544a, serta Sel Punca Kanker terhadap Respons Kemoterapi Berbasis Platinum Kanker Paru Jenis Karsinoma Bukan Sel Kecil (KPKBSK) Stage Lanjut = The Role of MicroRNA-224 dan MicroRNA-544a and Its Stemness to the Resistance of Platinum-based Chemotherapy in Patient with Advanced Stage Non-Small Cell Lung Cancer.

Kanker paru merupakan penyebab kematian terbanyak akibat kanker di dunia, dengan angka ketahanan hidup 5 tahun masih di bawah 15%. Kemoterapi pada KPKBSK yang digunakan saat ini adalah kemoterapi berbasis platinum, dikombinasikan dengan obat kemoterapi lain. Perlu dilakukan pemeriksaan ekspresi miR-224, miR-544a, GSK-3β, β-catenin dan CD44 pada jaringan tumor pasien KPKBSK stage lanjut, serta kaitannya dengan respons terhadap kemoterapi berbasis platinum menggunakan kriteria RECIST. Penelitian ini menggunakan desain kasus kontrol retrospektif dengan subjek 62 pasien KPKBSK, yang dikategorikan 25 pasien respons buruk sebagai kelompok kasus, 37 pasien respons baik sebagai kelompok kontrol. Didapatkan ekspresi penanda sel punca kanker (SPK) dengan imunohistokimia (IHK) pulasan β-catenin di nukleus dan CD44 di membran, meskipun tidak didapatkan korelasi yang bermakna terhadap respons kemoterapi. Didapatkan kaitan yang bermakna antara ekspresi IHK GSK-3β di sitoplasma dengan jenis kelamin, stage, dan subtipe histopatologis. Tidak terdapat hubungan signifikan antara ekspresi miR-224 atau miR-544a dengan ekspresi GSK- 3β, β-catenin di nukleus, dan CD44. Ekspresi miR-224 dan miR-544a, yang dievaluasi menggunakan RT-qPCR, menunjukkan perbedaan signifikan dalam respons terhadap kemoterapi berbasis platinum pada pasien KPKBSK stage lanjut. Ekspresi miR-544a berpotensi sebagai penanda respons buruk terhadap kemoterapi pada pasien KPKBSK stage lanjut EGFR wild-type, ke depannya miR-544a diharapkan dapat menjadi alternatif terapi target.
Kata kunci: Kemoterapi berbasis platinum, KPKBSK stage lanjut, Micro-RNA, RECIST, WNT/-catenin.


Lung cancer remains the predominant cause of cancer-related mortality globally, with a 5-year survival rate still under 15%. Current treatment for advanced nonsmall cell lung cancer (NSCLC) involves platinum-based chemotherapy combined with other chemotherapeutic agents. There is a need to examine the expression levels of miR-224, miR-544a, GSK-3β, β-catenin, and CD44 in tumor tissues of patients with advanced-stage NSCLC, and to investigate their association with the response to platinum-based chemotherapy using RECIST criteria. This study employed a retrospective case-control design with 62 NSCLC patients, divided into 25 patients with poor response as the case group and 37 patients with good response as the control group. Cancer stem cell markers (CSCs) were identified using immunohistochemistry (IHC), with β-catenin staining in the nucleus and CD44 in the membrane, although no significant correlation with chemotherapy response was detected. A significant association was observed between IHC expression of GSK- 3β in the cytoplasm and factors such as gender, stage, and histopathological subtype. There was no significant relationship between the expression of miR-224 or miR-544a and the expression of GSK-3β, nuclear β-catenin, and CD44. However, the expression levels of miR-224 and miR-544a, assessed using RTqPCR, showed significant differences in response to platinum-based chemotherapy in advanced-stage NSCLC patients. Specifically, miR-544a expression has the potential to serve as a marker for poor response to chemotherapy in advanced-stage EGFR wild type NSCLC patients, suggesting that miR-544a could be a future target for alternative therapy.
Key words: Advanced stage NSCLC, Micro-RNA, platinum-based chemotherapy, RECIST, WNT/β-catenin