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1/11

MARKER PROTEIN SERUM UNTUK

DETEKSI KANKER OVARIUM


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PENDAHULUAN

Ca ovariumkematian kanker ginekologi dan

kematian terbanyak akibat kanker pada wanita

Eropa dan AS

Diagnosis dini epithelial ovarian cancer (EOC)

secara signifikan morbiditas dan mortalitas

Biomarker potensial dx ca ovarium tp sedikit yg

dapat mendeteksi sebagai skrining stadium awal


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DETEKSI DINI CA OVARIUM

Mayoritas (85-95%) tumor ovarium malignan di

Amerika tipe epitelial

Metode deteksi dini imunologi ca ovarium pmxantigen yg berhubungan dg tumor, CA-125

CA-125 meningkat pd


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Serum Protein Marker untuk Deteksi Dini

Ca Ovarium

Analisis sampel serum dg spektrometri mencari

protein atau fragmen protein mendeteksi

keberadaan atau tidak adanya kanker

Alnalisis ada tidaknya suatu protein atau peptida

dlm serum antibodi ELISA atau pendekatan lain

sebagai kombinasi biomarker dg peningkatan

spesifitas dan sensitivitas CA-125 terhadap ca

ovarium


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Populasi Pasien

Sampel serum 86 orang, 28 sehat dan bebas

penyakit, 18 dx EOC stadium III/IV dan 40pasien dg EOC rekuren III/IV

+ adisional cohort dari 40 individu (8 sehat, 32

pasien EOC, std I-II) validasi blind set marker

Material dan metode

10 ml darah disentrifugal 800x 10 mnt serum

akan terseparasi, disimpan -80C Bank jaringanOB/GYN Yale University School of Medicine


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HASIL

Total 169 protein dianalisis Cytokin Rolling CircleAmplification (RCA) Microarrays, ELISA dan analisisstatistik.

35 protein--markerkelompok sehat dan pasien EOCberdasarkan tes ANOVA dengan nilai P


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Fig. 1.Four tumor markers identified for which the RCA microarray data and ELISA

data were completely concordant in classifying serum from normal and EOC

individuals in the training cohort. Microarray data are expressed as median

fluorescence intensity (mfl); ELISA data are expressed as average protein
http://www.pnas.org/content/vol102/issue21/images/large/zpq0170581130001.jpeghttp://www.pnas.org/content/vol102/issue21/images/large/zpq0170581130001.jpeg


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Tabel Split Poin

Marker Split point Left interval Right interval

Leptin 2.5 Cancer (1) Normal (0)

Prolactin 10 Normal (0) Cancer (1)

OPN 21 Normal (0) Cancer (1)

IGF-II 491 Cancer (1) Normal (0)

The split-point scoring procedure is as follows. For each marker, find the best split point to

minimize the number of misclassified individuals. The split point divides the sample spaceinto two intervals: one for normal and another for cancer. A score of 0 is assigned to anindividual if the related analyte value falls in the normal interval; otherwise, a score of 1 isassigned. Overall, an individual is assigned a score as the sum of the assigned scoresfrom four different markers, the range of such scores being 0-4.


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40 sampel -- analisis klasifikasi split poin

Hasil 37 dari 40 sampel tepat diidentifikasi (94%)

Fig. 3.Four-analyte split-point analysis of serum from healthy women (Healthy) and womenwith EOC (Cancer). Correctly classified normal serum should have a score of 0 or 1, whereassamples from cancer patients have a score of 2, 3, or 4. False-positive and false-negativesamples are readily detected.
http://www.pnas.org/content/vol102/issue21/images/large/zpq0170581130003.jpeg


10/11

DISKUSI

Ca ovarium relatif asimtomatik -- monitoring dan deteksidini yang tepat

Tes harus dapat mendeteksi secara akurat perubahan

dari pre malignan atau ca ovarium std dini asimtomatik --- ca ovarium

Analisis 4 biomarker hasil skrining signifikan

+ Ca 125 atau protein lain mengimplikasi diskriminasi

EOC mempertegas sensitivitas/spesifitas tes tsb

Skrining diperlukan juga pemeriksaan tambahan sepertiUSG transvaginal


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SIMPULAN

Marker diskriminasi ca ovarium dan normaldilaporkan disini mungkin bukan merupakanmarker spesifik untuk EOC

Set protein akurasi tinggi dapat membedakanantara pasien EOC dan normal (std I dan II)

Uji serum empat protein markersensitivitas 95%, spesifitas 95%, PPV 95%,dan nilai prediktif negatif 94% .

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