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Sains Malaysiana 55(4)(2026): 689-705
http://doi.org/10.17576/jsm-2026-5504-09
Differential Expression of
GDF-15, PSAP, and COL6A1 in Prostate Cancer Cells and TNMplot-Based
Clinical Tissue Specimens of Prostate Cancer Adenocarcinoma
(Ekspresi Berbeza GDF-15, PSAP dan
COL6A1 dalam Sel Kanser Prostat dan Spesimen Tisu Klinikal Berasaskan TNMplot bagi Adenokarsinoma Kanser Prostat)
NEGIN
KAVOUSIGHAHFAROKHI1, AYUNI SYAFIQAH ROSLI@PAZLI2, NUR
ARIESYA AQUILA ZAINAL2, ADLINA ROSLAN1, DIANA SUHAIZA
SAID1, MUHAMMAD IRFAN RAZIQ AZMAN2, LATIFAH SAIFUL YAZAN2 & ARMANIA NURDIN1,2,*
1Laboratory of UPM-MAKNA Cancer Research (CANRES), Institute of
Bioscience, Universiti Putra
Malaysia, 43400 UPM Serdang, Selangor, Malaysia
2Department
of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor,
Malaysia
Received:
6 June 2025/Accepted: 8 April 2026
Abstract
Distinguishing aggressive from indolent prostate
cancer remains a key clinical challenge. Although prostate-specific antigen
(PSA) is commonly used for diagnosis, its low sensitivity and specificity limit
its ability to predict tumour aggressiveness. This study aimed to investigate
the expression patterns of selected protein biomarkers, including
growth/differentiation factor-15 (GDF-15), prosaposin (PSAP), and collagen-α1
(VI) chain (COL6A1), in prostate cancer cells (primary and metastatic) and
tumour tissue samples. The immunocytochemical (ICC) analysis showed distinct
expression patterns of these proteins across different prostate cancer cell
lines, with GDF-15 being highly expressed in lymph node metastatic (LNCaP)
cells. In contrast, PSAP and COL6A1 were primarily expressed in primary (22Rv1)
and bone metastatic (PC-3) cells. The western blot analysis confirmed differential
expression of GDF-15, PSAP, and COL6A1 across prostate cancer cell lines, with
GDF-15 showing higher expression in LNCaP cells, whereas PSAP and COL6A1 were
highly expressed in PC-3 cells. TNMplot analysis showed
that the GDF-15 gene was significantly upregulated in primary and
metastatic prostate cancer tissues compared to non-tumour samples and was also
markedly overexpressed in colon adenocarcinoma. Similarly, PSAP expression was elevated in primary prostate tumours relative to non-tumour
tissues, with significantly higher levels observed in hepatocellular carcinoma.
In contrast, COL6A1 was consistently downregulated in prostate cancer
tissues and across several other malignancies. These results suggest that
GDF-15 may serve as a broad-spectrum cancer biomarker, whereas PSAP and COL6A1
may be associated with disease progression and metastatic behaviour. However,
further studies are needed to validate their potential clinical applications as
a biomarker.
Keywords: Prostate cancer;
protein biomarkers; COL6A1; GDF-15; PSAP
Abstrak
Membezakan antara kanser prostat yang agresif dan tidak agresif kekal sebagai cabaran klinikal utama. Walaupun antigen khusus prostat (PSA) lazimnya digunakan untuk diagnosis, kepekaan dan pengkhususan yang rendah mengehadkan kemampuannya untuk meramalkan tahap agresif tumor. Penyelidikan ini bertujuan untuk mengkaji corak ekspresi biopenanda protein terpilih, termasuk pertumbuhan/faktor pembezaan 15 (GDF-15), prosaposin (PSAP) dan kolagen-α1 (VI) rantaian (COL6A1) dalam sel kanser prostat (primer dan metastatik) serta sampel tisu tumor. Analisis imunositokimia (ICC) menunjukkan corak ekspresi yang berbeza bagi biopenanda protein tersebut dalam pelbagai sel kanser prostat dengan GDF-15 didapati sangat tinggi dalam sel metastatik nodus limfa (LNCaP). Sebaliknya, PSAP
dan COL6A1 terutamanya dijumpai dalam sel primer (22Rv1)
dan sel metastatik tulang (PC-3) yang menunjukkan potensi peranan dalam perkembangan dan pengkhususan metastatik kanser prostat. Analisis pemendapan Western mengesahkan ekspresi yang berbeza bagi GDF-15, PSAP dan
COL6A1 dalam pelbagai sel kanser prostat dengan GDF-15 menunjukkan ekspresi yang lebih tinggi dalam sel LNCaP, manakala PSAP dan COL6A1 pula menunjukkan ekspresi yang tinggi dalam sel PC-3. Analisis TNMplot menunjukkan bahawa gen GDF-15 meningkat secara ketara dalam tisu kanser prostat primer dan metastatik berbanding sampel bukan tumor serta turut menunjukkan ekspresi berlebihan yang ketara dalam adenokarsinoma kolon. Begitu juga dengan ekspresi PSAP yang didapati meningkat dalam tumor prostat primer berbanding tisu bukan tumor dengan tahap yang jauh lebih tinggi diperhatikan dalam karsinoma hepatosel. Sebaliknya, COL6A1 secara tekal didapati menurun dalam tisu kanser prostat serta pelbagai jenis kanser lain. Keputusan ini mencadangkan bahawa GDF-15 berpotensi sebagai biopenanda kanser spektrum luas, manakala PSAP dan COL6A1 mungkin berkaitan dengan perkembangan penyakit dan tingkah laku metastatik. Walau bagaimanapun, kajian lanjut diperlukan untuk mengesahkan potensi aplikasi klinikal bagi biopenanda ini.
Kata kunci: Biopenanda protein; kanser prostat; COL6A1; GDF-15; PSAP
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*Corresponding author; email: armania@upm.edu.my
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