J Korean Med Sci.  2013 Jul;28(7):1005-1014. 10.3346/jkms.2013.28.7.1005.

Transglutaminase 2 Expression Predicts Progression Free Survival in Non-Small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

• Jeong JH
• Cho BC
• Shim HS
• Kim HR
• Lim SM
• Kim SK
• Chung KY
• Islam SM
• Song JJ
• Kim SY
• Kim JH

• KMID: 1777495
• DOI: http://doi.org/10.3346/jkms.2013.28.7.1005

Abstract

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-kappaB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.

Keyword

Transglutaminase 2; NF-kappaB; Lung Neoplasms

MeSH Terms

Adenocarcinoma/*drug therapy/mortality/surgery
Adult
Aged
Aged, 80 and over
Antineoplastic Agents/therapeutic use
Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/surgery
Disease-Free Survival
Female
GTP-Binding Proteins/*biosynthesis
Humans
Lung Neoplasms/*drug therapy/mortality/surgery
Male
Middle Aged
NF-kappa B/biosynthesis
Protein Kinase Inhibitors/therapeutic use
Receptor, Epidermal Growth Factor/*antagonists & inhibitors/genetics
Transglutaminases/*biosynthesis
Treatment Outcome
Antineoplastic Agents
GTP-Binding Proteins
NF-kappa B
Protein Kinase Inhibitors
Receptor, Epidermal Growth Factor
Transglutaminases

Figure

• 

  Fig. 1 Immunohistochemical staining for nuclear factor kappa B (NF-κB) subunit p65 (A) and transglutaminase 2 (TG2) (C) in patients with primary lung cancer. Cytoplasmic staining of varying intensity is evident in the cancer cells. Immunohistochemical-negative staining for NF-κB subunit p65 (B) and TG2 (D) in patients with primary lung cancer.

• 

  Fig. 2 Kaplan-Meier plot showing disease-free survival according to NF-κB level (A) and TG2 level (B). Progression-free survival (PFS) in patients with platinum-based doublet chemotherapy is shown according to NF-κB level (C) and TG2 level (D).

• 

  Fig. 3 Kaplan-Meier plot showing PFS in patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy according to EGFR mutation status, NF-κB level, and TG2 level (A, B, C, respectively). Kaplan-Meier plot showing PFS in patients with EGFR-TKI therapy according to NF-κB level and TG2 level in patients positive for the EGFR mutation (D, E, respectively) and EGFR wild-type patients (F, G, respectively). NA, not available.

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