Disertasi

Pengaruh Konsentrasi MiR-21, MiR-145, Large Tumor Suppressor 1, dan Nuclear Factor Kappa B serta Usia terhadap Respons Kemoradiasi pada Pasien Kanker Serviks Uteri Stadium Lanjut Lokal = The Influence ofMiR-21, MiR-145, Large Tumor Suppressor 1, Nuclear Factor Kappa B, and Age on Chemoradiation Response in Patients with Locally Advanced Stage Cervical Cancer.

Kanker serviks merupakan salah satu kanker terbanyak pada perempuan dengan jumlah kasus dan kematian yang bermakna, terutama di negara-negara berkembang seperti Indonesia. Penelitian terbaru menyoroti peran mikroRNA (miRNA) dalam karsinogenesis, terutama miR-21 yang terlibat dalam berbagai jenis kanker pada perempuan, termasuk kanker serviks. Selain itu, miR-145, LATS1, dan NF-κB dipercaya memiliki peran dalam radioresistensi. Penelitian ini bertujuan untuk membuktikan pengaruh konsentrasi miR-21, miR-145, Large Tumor Suppressor 1 (LATS1), dan Nuclear Factor Kappa B (NF- kB) serta usia terhadap respons kemoradiasi pada pasien kanker serviks stadium lanjut lokal. Penelitian ini menggunakan desain potong lintang analitik yang dilakukan di Rumah Sakit Cipto Mangunkusumo dari bulan Juli 2017 sampai Juni 2023. Sampel jaringan dari biopsi serviks diambil dan diperiksa menggunakan real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) untuk mendeteksi miR-21 dan miR-145, serta ELISA untuk mendeteksi konsentrasi LATS1 dan NF- kB sebelum pasien menerima terapi kemoradiasi. Pemeriksaan ultrasonografi kemudian dilakukan kembali untuk menilai respons radiasi dengan menggunakan kriteria RECIST 1.1. Dari 140 subjek, ditemukan gambaran histopatologi karsinoma sel skuamosa pada 119 (85%) sampel, dengan distribusi kanker serviks stadium IIIB pada 102 (72,9%) subjek dan stadium IVA pada 38 (27,1%) subjek. Ekspresi miR- 21 di atas cut-offlebih banyak ditemukan pada subjek yang radioresisten (p = 0,010; AUC = 67,6%). Ekspresi miR-145 dan LATS1 di atas cut-off lebih banyak ditemukan pada kelompok radioresisten, masing-masing dengan p = 0,132 (AUC = 38,8%) dan p = < 0,001 (AUC = 32,7%). Ekspresi NF- kB di bawah cut-off ditemukan lebih banyak pada kelompok radioresisten (p = 0,009; AUC = 61%), dan usia di bawah cut-offjuga lebih banyak ditemukan pada kelompok radioresisten (p = 0,138; AUC = 39,2%). Penelitian ini menunjukkan bahwa ekspresi miR-21 dan LATS1 pra-kemoradiasi yang tinggi serta ekspresi NF-κB yang rendah berhubungan dengan terjadinya radioresistensi. Sebaliknya, konsentrasi miR-145 dan usia tidak berhubungan dengan radioresistensi, sehingga dapat disimpulkan bahwa miR-21 memiliki potensi sebagai biomarker radioresisten pada pasien kanker serviks stadium lanjut lokal dan pemeriksaan kombinasi tidak disarankan.
Kata Kunci: kanker serviks, LATS1, miR-21, miR-145, NF-κB


Cervical cancer is one of the most common cancers in women with a significant number of cases and deaths, especially in developing countries such as Indonesia. Recent research highlights the role of microRNAs (miRNAs) in carcinogenesis, particularly miR-21, which is involved in various types of cancer in women, including cervical cancer. In addition, miR-145, LATS1 and NF-κB also considered to play a role in radioresistance. This study aims to determine the influence ofmiR- 21, miR-145, Large Tumor Suppressor 1 (LATS1), Nuclear Factor Kappa B (NF- κB), and age on chemoradiation response in locally advanced cervical cancer patients. This study used an analytical cross-sectional design conducted at Cipto Mangunkusumo Hospital from July 2017 to June 2023. Cervical biopsy tissue samples were collected and examined using real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to detect miR-21 and miR-145, and ELISA to measure LATS1 and NF-κB concentrations before patients underwent chemoradiation therapy. Ultrasound examination was then re-performed to assess radiation response using RECIST 1.1 criteria. This research obtained a total of 140 samples with histopathological subtype of squamous cell carcinoma found in 119 (85%) samples, with cervical cancer stage IIIB in 102 (72.9%) subjects and stage IVA in 38 (27.1%) subjects. Expression of miR-21 above the cut-off was more prevalent in radioresistant patients (p = 0.010; AUC = 67.6%). Expression of miR-145 and LATS1 above the cut-offwere found to be higher in the radioresistant group with p = 0.132 (AUC = 38.8%) and p = < 0.001 (AUC = 32.7%), respectively. NF-κB expression below the cut-off were found to be higher in the radioresistant group (p = 0.009; AUC = 61%), and age below the cut-off were also found to be higher in the radioresistant group (p = 0.138; AUC = 39.2%). This study showed that high expression ofmiR-21 and LATS1 pre-chemoradiation and low expression of NF-κB pre-chemoradiation were all associated with radioresistance, while miR- 145 concentration and age were not associated with radioresistance. This study concluded that miR-21 had the potential to be used as a radioresistant biomarker in patients with local advanced-stage cervical cancer and combination testing was not suggested.
Keyword: cervical cancer, LATS1, miR-21, miR-145, NF-kB