Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients

Abstract

Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Cigarette smoking is the number one risk factor which is attributed to more than four out of five cases of lung cancers. The prognostic impact of cell cycle regulation-associated tumor suppressors including p53 and p21 for NSCLC is still controversial. In the present study, we examined p53 and p21 expression using immunoblotting in tumor and adjacent non-cancerous tissues from NSCLC patients. Moreover, tissue microarrays (TMAs) including 150 specimens was used to examine p53 and p21 expression by immunohistochemical staining (IHC). The association between p53/p21 and various clinicopathological characteristics was evaluated. Kaplan-Meier overall survival was used to analyze the association between p53/p21 expression and prognosis of NSCLC patients, as well as the association of cigarette smoking with p53/p21 expression and prognosis. The results of the immunoblotting showed that expression of p53 and p21 in tumor tissues was significantly higher than that in the matched adjacent non-cancerous tissues (P<0.001 and P<0.05, respectively). The IHC results showed that 50.67% of the cases had high expression of p21; however, the percentage of patients having high expression of p53 was 31.3%. Univariate and Cox regression models were used to evaluate the factors related to prognosis with p53 and p21 expression. Multivariate analysis indicated that p53 expression was an independent prognostic factor for NSCLC (P=0.005), while p21 could not serve as an independent prognostic factor (P=0.123). In addition, smoking history was closely related to lung cancer risk (P=0.041), but could not be an independent assessment factor (P=0.740). In this study, we further demonstrated the association of p53/p21 expression and cigarette smoking. Our results suggest that cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis. The combination of p53/p21 expression and smoking history may be a useful biomarker for tumor progression and prognosis of NSCLC patients.

M2 polarized macrophages induced by CSE promote proliferation, migration, and invasion of alveolar basal epithelial cells

“…Lung cancer is the most frequently occurring malignant cancer and is the leading cause of cancer death worldwide [15,16]. Cigarette smoke contains more than 100 different mutagens and carcinogens and is the cause of approximately 90% of lung cancer cases [16,17].…”

Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non‐small cell lung cancer (NSCLC)

“…The malignant transformation of NSCLC is a complicated multifactor, multistep process involving multiple genes. 19 The predominant reason for carcinogenesis can be attributed to the down-regulation of tumor suppressor genes and the upregulation of oncogenes or cancer-promoting genes. 20 The DPP4 enzyme family is expressed and is found in all normal human adult and neonatal tissues.…”

Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway

“…Therefore, the G1 checkpoint is important for tumor suppression (38). Previous studies (11,22) have determined that the p21 gene is associated with tumor differentiation, depth of invasion, proliferation and metastasis of tumors, and is also valuable as a prognostic sign for tumor progression.…”

“…A mutation in the p21 gene is associated with pancreatic cancer (10) and the differentiation of other malignant tumor types, including to the depth of invasion, proliferation and metastasis. Additionally, p21 has prognostic value; p21 expression has been documented as a poor prognostic marker in human lung cancer (11). Proliferating cell nuclear antigen (PCNA) is a protein expressed in proliferative stage cells or tumor cells (12).…”