Meme İnvaziv Karsinomunda Plektin İzofom 1d’nin Evre-Spesifik Ekspresyon Profili, Prognostik Değeri ve İnvaziv Fenotiple Olan Potansiyel İlişkisi

Abstract

Bu çalışma, meme invaziv karsinomunda (BRCA) PLEC geni 1d (PLEC 1d) izoformunun evreye özgü ekspresyon profilini, prognostik önemini ve invaziv fenotiple ilişkisini araştırmayı amaçlamıştır. The database for differentially expressed isoforms and genes in human cancers (Cancer DEIso) veritabanı kullanılarak TCGA verileri üzerinden PLEC 1d’nin evre bazında (I–IV) ekspresyon farklılıkları ve logrank testi ile sağkalım analizleri yapılmıştır. Ayrıca MCF7, MDA-MB-231 ve MCF10A hücre hatlarında PLEC 1d mRNA ifade düzeyleri RT-qPCR ile, total plectin protein düzeyleri ise Western blot ile değerlendirilmiştir. Bulgulara göre, PLEC 1d mRNA ifadesi tüm evrelerde normal dokuya kıyasla anlamlı derecede yüksek bulunmuştur. Sağkalım analizi, evre I (p: 0,712) ve evre IV’te (p: 0,947) anlamlı bir ilişki göstermezken, evre II (p: 0,006) ve evre III’te (p: 0,041) yüksek ekspresyonun daha kötü prognozla ilişkili olduğunu ortaya koymuştur. Bununla birlikte, yüksek metastatik MDA-MB-231 hücre hattında, daha az invaziv MCF7 hücrelerine kıyasla PLEC 1d mRNA ifadesi belirgin şekilde artmıştır (p: 0.001). Total plectin protein düzeyleri, MCF10A’ya göre her iki kanser hücre hattında daha yüksek olup, en yüksek seviye MDA-MB-231’de gözlenmiştir. Sonuç olarak, PLEC 1d ekspresyonu BRCA’da evreye bağımlı prognostik etki göstermekte olup, özellikle evre II ve III’te önemli bir belirteç adayıdır. İnvaziv fenotiple ilişkisi, bu izoformun tümör ilerlemesinde işlevsel rol oynayabileceğini düşündürmektedir. PLEC 1d, metastatik BRCA için potansiyel bir biyobelirteç ve tedavi hedefi olarak değerlendirilmelidir.

Keywords

• Meme Kanseri
• plectin 1d
• ekspresyon
• metastaz

Supporting Institution

Finansal destek alınmamıştır.

Ethical Statement

Çalışmada yalnızca hücre hatları ve in silico analizler kullanıldığı için etik kurul izni gerekmemektedir.

Stage-Dependent Expression Profile, Prognostic Value and Potential Association with Invasive Phenotype of Plectin Isoform 1d in Breast Invasive Carcinoma

Abstract

This study aimed to investigate the stage-specific expression profile, prognostic significance, and association with invasive phenotype of the PLEC gene isoform 1d (PLEC 1d) in breast invasive carcinoma (BRCA). Stage-specific differential expression of PLEC 1d (stages I–IV) and survival analyses using the logrank test were performed on TCGA data via the database for differentially expressed isoforms and genes in human cancers (Cancer DEIso). Additionally, PLEC 1d mRNA expression was assessed by qRT-PCR, and total plectin protein levels were evaluated by Western blot in MCF7, MDA-MB-231, and MCF10A cell lines. The results demonstrated that PLEC 1d expression was significantly elevated in tumor tissues across all stages compared to normal tissue. Survival analysis revealed no significant association in stage I (p: 0.712) or stage IV (p: 0.947); however, higher expression was significantly associated with worse prognosis in stage II (p: 0.006) and stage III (p: 0.041). However, the highly metastatic MDA-MB-231 cell line exhibited significantly higher PLEC 1d mRNA expression levels than the less invasive MCF7 cells (p: 0.001). Total plectin protein levels were higher in both cancer cell lines relative to MCF10A, with the highest levels observed in MDA-MB-231 cells. In conclusion, PLEC 1d expression exerts stage-dependent prognostic effects in BRCA, with significant impact during stages II and III. Its association with an invasive phenotype suggests a functional role in tumor progression. Therefore, PLEC 1d should be considered a potential biomarker and therapeutic target in metastatic BRCA.

Keywords

• BRCA
• plectin 1d
• expression

Supporting Institution

This study did not receive any financial support.

Ethical Statement

Only commercially available cell lines and in silico analyses were used in this study; consequently, ethical approval was not required.

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