Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most widespread cancer with increasing morbidity and mortality. FAS-associated protein with death domain (FADD) is considered as an essential instrument in cell death, whereas Bcl-XS promotes apoptosis through inhibiting the activity of Bcl-2 and Bcl-XL. OBJECTIVE AND METHODS: We detected the expression of FADD and Bcl-XS in resected NSCLC tissues by immunohistochemistry, and investigated their association with clinicopathological characteristics and prognostic significance of NSCLC patients. RESULTS: Bcl-XS expression was significantly increased in well and moderate differentiated lung SCC (P= 0.004). Lung ADC patients with overexpression of FADD and lung SCC patients with low expression of Bcl-XS had importantly lower overall survival rates by Kaplan-Meier analysis (P= 0.033, P= 0.02, respectively). Multivariate analysis confirmed that elevated expression of FADD was an independent poor prognostic factor for patients with surgically resected lung ADC (P= 0.027) and increased expression of Bcl-XS was an independent good prognostic factor for patients with surgically resected lung SCC (P= 0.016) CONCLUSION: Elevated expression of FADD was identified as independent poor prognostic factor for patients with surgically resected lung ADC, however, increased expression of Bcl-XS was an independent good prognostic biomarker for patients with surgically resected lung SCC.

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Loss of PTEN Expression is an Independent Poor Prognostic Factor in Non-small Cell Lung Cancer

The Korean Journal of Pathology ◽

10.4132/koreanjpathol.2011.45.4.329 ◽

2011 ◽

Vol 45 (4) ◽

pp. 329 ◽

Cited By ~ 8

Author(s):

Seol Bong Yoo ◽

Xianhua Xu ◽

Hyun Ju Lee ◽

Sanghoon Jheon ◽

Choon-Taek Lee ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Pten Expression ◽

Small Cell Lung ◽

Poor Prognostic Factor ◽

Independent Poor Prognostic Factor

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Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non–Small-Cell Lung Cancer Tumors

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.4133 ◽

2006 ◽

Vol 24 (2) ◽

pp. 306-314 ◽

Cited By ~ 107

Author(s):

Junji Tsurutani ◽

Junya Fukuoka ◽

Hiroko Tsurutani ◽

Joanna H. Shih ◽

Stephen M. Hewitt ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Prognostic Significance ◽

Small Cell ◽

Surrounding Tissue ◽

Small Cell Lung ◽

Poor Prognostic Factor ◽

Akt Activation

Purpose Akt is a serine/threonine kinase that has been implicated in lung tumorigenesis and lung cancer therapeutic resistance. Full activation of Akt requires two phosphorylation events, but only one site of phosphorylation (S473) has been evaluated thus far in clinical non–small-cell lung cancer (NSCLC) specimens, which has resulted in conflicting results regarding the prognostic significance of Akt activation in NSCLC. In this study, we sought to determine whether evaluation of Akt phosphorylation at T308 would improve prognostic accuracy. Patients and Methods Phosphospecific antibodies against T308 and S473 were validated and used in an immunohistochemical analysis of tissue microarray slides containing NSCLC specimens (n = 300) and surrounding lung tissue specimens (n = 100). Results Phosphorylation of either S473 or T308 was positive in most NSCSLC specimens, but was detected rarely in surrounding normal tissues. When Akt activation was defined by using both sites of phosphorylation, Akt activation was specific for NSCLC tumors versus surrounding tissue (73.4% v 0%; P < .05), was higher in adenocarcinoma than in squamous cell carcinoma (78.1% v 68.5%; P = .040), and was associated with shorter overall survival for all stages of disease (log-rank P = .041). In multivariate analyses, increased phosphorylation of T308 alone was a poor prognostic factor for stage I patients or for tumors < 5 cm (log-rank P = .011 and P = .015, respectively). Conclusion These results suggest that monitoring phosphorylation of Akt at T308 improves the assessment of Akt activation, and show that Akt activation is a poor prognostic factor for all stages of NSCLC.

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Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21197025 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7025

Author(s):

Katarzyna Ratajczak-Wielgomas ◽

Alicja Kmiecik ◽

Jedrzej Grzegrzołka ◽

Aleksandra Piotrowska ◽

Agnieszka Gomulkiewicz ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factor ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Prognostic Significance ◽

Immunohistochemical Analysis ◽

Small Cell ◽

Small Cell Lung

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

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