Journals / Düzce Tıp Fakültesi Dergisi / 2023 / Cilt: 25 Sayı: 2

The Expression of Caspase-3 and GRIM-19 in Non-mucinous Lung Adenocarcinoma and Their Clinicopathologic Significance

Müsinöz Olmayan Akciğer Adenokarsinomlarında Caspase-3 ve GRIM-19 Ekspresyonu ile Bu Proteinlerin Klinikopatolojik Önemi

Pages
158–166
Publication Date
2023-08-30
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The overall 5-year survival rate of patients with low and high GRIM-19 expression tumors was 48% and 92%, respectively.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Aim: The current study aimed to investigate apoptotic proteins such as caspase-3 and GRIM-19 protein expression in non-mucinous lung adenocarcinomas and their clinicopathologic significance.
📊
Key Findings & Data:Material and Methods: This study was performed on 81 patients diagnosed with non-mucinous lung adenocarcinoma between January 1, 2010, and June 1, 2020.
💡
Conclusion & Impact:The overall 5-year survival rate of patients with low and high GRIM-19 expression tumors was 48% and 92%, respectively.
🔬Design:Research Article
📍Scope:2010 Verileri
⚙️Variables:Apoptosis · Caspase-3 · GRIM-19

Abstract

Aim: The current study aimed to investigate apoptotic proteins such as caspase-3 and GRIM-19 protein expression in non-mucinous lung adenocarcinomas and their clinicopathologic significance. Material and Methods: This study was performed on 81 patients diagnosed with non-mucinous lung adenocarcinoma between January 1, 2010, and June 1, 2020. Immunohistochemical analysis was performed to examine the expressions of caspase-3 and GRIM-19, and the association between these proteins and clinicopathological parameters was investigated. Results: Caspase-3 nuclear positivity was more common in high-grade non-mucinous lung adenocarcinomas (p<0.001). Caspase-3 cytoplasmic expression was stronger in tumors with advanced-stage (p=0.021) and lymph node metastases (p=0.020). GRIM-19 expression was low in tumors with high-grade non-mucinous lung adenocarcinomas (p=0.002), and tumors with lymphovascular invasion (p=0.021). The median follow-up time was 31.7 (range, 1-145 months. The overall 5-year survival rate of patients with low and high GRIM-19 expression tumors was 48% and 92%, respectively. GRIM-19 expression significantly affected the 5-year overall survival rate (p=0.008), but not the 5-year disease-free survival rate (p=0.368). Conclusion: We revealed a significant association between caspase-3 and GRIM-19 expressions and poor clinicopathologic features and prognosis. For the first time in the literature, we revealed an association between low GRIM-19 expression and worse clinical outcomes in patients with non-mucinous lung adenocarcinoma. Caspase-3 and GRIM-19 may become potential therapeutic targets and novel potential predictive biomarkers for non-mucinous lung adenocarcinoma patients.

Özet

Amaç: Bu çalışmada, müsinöz olmayan akciğer adenokarsinomlarında, apoptotik protein olarak bilinen caspase-3 ve GRIM-19 protein ekspresyonu ve bu proteinlerin klinikopatolojik öneminin araştırılması amaçlandı. Gereç ve Yöntemler: Bu çalışma, 1 Ocak 2010 ile 1 Haziran 2020 tarihleri arasında müsinöz olmayan akciğer adenokarsinomu tanısı alan 81 hasta üzerinde gerçekleştirildi. Caspase-3 ve GRIM-19 ekspresyonlarını incelemek için immünohistokimyasal analiz yapıldı ve bu proteinler ile klinikopatolojik parametreler arasındaki ilişki araştırıldı. Bulgular: Caspase-3 nükleer pozitifliği yüksek dereceli müsinöz olmayan akciğer adenokarsinomlarında daha yaygın bulundu (p<0,001). Caspase-3 sitoplazmik ekspresyonu ileri evre (p=0,021) ve lenf nodu metastazı (p=0,020) olan tümörlerde daha güçlü saptandı. GRIM-19 ekspresyonu, yüksek dereceli müsinöz olmayan akciğer adenokarsinomlu tümörlerde (p=0,002) ve lenfovasküler invazyonlu tümörlerde (p=0,021) düşük idi. Ortanca takip süresi 31,7 (aralık, 1-145) ay idi. Düşük ve yüksek GRIM-19 ekspresyonlu tümörlere sahip hastaların 5 yıllık genel sağkalım oranı sırasıyla %48 ve %92 idi. GRIM-19 ekspresyonu genel 5 yıllık sağkalım oranı üzerinde anlamlı bir etkisi olduğu (p=0,008), ancak 5 yıllık hastalıksız sağkalım oranı üzerinde anlamlı bir etkisi olmadığı (p=0,368) saptandı. Sonuç: Caspase-3 ve GRIM-19 ekspresyonu ile kötü klinikoptolojik özellikler ve prognoz arasında anlamlı bir ilişki olduğunu gösterdik. Literatürde ilk kez, düşük GRIM-19 ekspresyonunun müsinöz olmayan akciğer adenokarsinomunda daha kötü bir klinik gidişle ilişkili olduğunu ortaya koyduk. Caspase-3 ve GRIM-19 müsinöz olmayan akciğer adenokarsinomu hastaları için yeni potansiyel prognostik biyobelirteçlerin yanı sıra potansiyel terapötik hedefler haline gelebilir.

🔖

Cite This Article

ATILGAN, A. O., TEPEOĞLU, M., AKÇAY, E. Y., HASANALİYEVA, L., KILIÇ, D., ÖZDEMİR, H. (2023). The Expression of Caspase-3 and GRIM-19 in Non-mucinous Lung Adenocarcinoma and Their Clinicopathologic Significance. Düzce Tıp Fakültesi Dergisi, Cilt: 25 Sayı: 2, 158–166. https://ajindex.com/articles/958553

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (13)

  1. WHO Classification of Tumours Editorial Board. Thoracic Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer; 2021.
  2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.
  3. Haura EB, Cress WD, Chellappan S, Zheng Z, Bepler G. Antiapoptotic signaling pathways in non-small-cell lung cancer: biology and therapeutic strategies. Clin Lung Cancer. 2004;6(2):113-22.
  4. Eskandari E, Eaves CJ. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J Cell Biol. 2022;221(6):e202201159. Boice A, Bouchier-Hayes L. Targeting apoptotic caspases in cancer. Biochim Biophys Acta Mol Cell Res. 2020;1867(6):118688. Liu X, Li F, Huang Q, Zhang Z, Zhou L, Deng Y, et al. Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells. Cell Res. 2017;27(6):764-83.
  5. Boudreau MW, Peh J, Hergenrother PJ. Procaspase-3 overexpression in cancer: a paradoxical observation with therapeutic potential. ACS Chem Biol. 2019;14(11):2335-48.
  6. Kalvakolanu DV, Nallar SC, Kalakonda S. Cytokine-induced tumor suppressors: a GRIM story. Cytokine. 2010;52(1-2):128-42.
  7. Sun P, Nallar SC, Raha A, Kalakonda S, Velalar CN, Reddy SP, et al. GRIM-19 and p16(INK4a) synergistically regulate cell cycle progression and E2F1-responsive gene expression. J Biol Chem. 2010;285(36):27545-52.
  8. Nallar SC, Kalvakolanu DV. GRIM-19: A master regulator of cytokine induced tumor suppression, metastasis and energy metabolism. Cytokine Growth Factor Rev. 2017;33:1-18.
  9. Lufei C, Ma J, Huang G, Zhang T, Novotny-Diermayr V, Ong CT, et al. GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. EMBO J. 2003;22(6):1325-35.
  10. Moreira S, Correia M, Soares P, Máximo V. GRIM-19 function in cancer development. Mitochondrion. 2011;11(5):693-9.
  11. Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV. Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem. 2000;275(43):33416-26.
  12. Huang Y, Yang M, Yang H, Zeng Z. Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line. Exp Cell Res. 2010;316(13):2061-70.
  13. Wang T, Yan XB, Zhao JJ, Ye J, Jiang ZF, Wu DR, et al. Gene associated with retinoid-interferon-induced mortality-19 suppresses growth of lung adenocarcinoma tumor in vitro and in vivo. Lung Cancer. 2011;72(3):287