High expression of CIP2A protein is associated with tumor aggressiveness in stage I-III NSCLC and correlates with poor prognosis

Abstract

The aim of this work was to examine the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in non-small cell lung cancer (NSCLC) and analyze its correlation with clinical outcomes. CIP2A protein levels were detected by immunohistochemistry (IHC). One hundred and eighty-four of 209 (88.3%) primary stage I-III NSCLC specimens and 4 of 38 (10.5%) adjacent normal lung tissue specimens expressed CIP2A protein. High expression of CIP2A was detected in 38.8% (81/209) of the NSCLC specimens. Patients diagnosed histologically with late-stage NSCLC (p<0.001) and malignant nodes (p=0.001) exhibited high CIP2A expression. Univariate analysis using the log-rank test identified CIP2A expression as a prognostic predictor for overall survival (p=0.005). In multivariate analyses using the Cox regression test, CIP2A expression, T stage, N stage, histological type, and chemotherapy were identified as independent prognostic factors (p=0.007, 0.001, 0.003, <0.001, and <0.001, respectively). Furthermore, Kaplan-Meier survival curves demonstrated that high CIP2A expression indicated poor prognosis in the subgroup of patients with squamous cell carcinoma (p=0.008). Similar results were noted in the subgroup of patients with adenocarcinoma, but the results did not reach statistical significance (p=0.084). We also used univariate analysis and multivariate analysis to assess the prognostic factors for overall survival in the subgroup of patients who received postoperative chemotherapy. CIP2A expression was also an independent prognostic factor in NSCLC patients who received postoperative chemotherapy (p=0.009), along with histological type (p=0.001) and N stage (p=0.034). In conclusion, adding to the accumulating evidence, our research suggested that the CIP2A expression is associated with aggressiveness and correlates with poor prognosis in NSCLC. Our findings also indicated that CIP2A might be a potential therapeutic target against NSCLC.

Keywords: CIP2A; chemotherapy; immunohistochemistry; non-small cell lung carcinoma; prognosis; radiotherapy.

Figure 1

Immunohistochemical staining of CIP2A in NSCLC specimens. Notes: Positive CIP2A protein staining was mainly observed in cytoplasm. (A and B) CIP2A expression in adjacent normal lung tissue. The final score is 0 (negative). (C and D) CIP2A expression in primary NSCLC tissues of pathologic stage I. The final score is 1 (1×1). (E and F) CIP2A expression in primary NSCLC tissues of pathologic stage II. The final score is 4 (2×2). (G and H) CIP2A expression in primary NSCLC tissues of pathologic stage III. The final score is 12 (4×3). Abbreviations: CIP2A, cancerous inhibitor of protein phosphatase 2A; NSCLC, non-small cell lung cancer.

Figure 2

Immunohistochemical staining of CIP2A in squamous cell carcinoma and adenocarcinoma. Notes: (A and B) Low expression of CIP2A in squamous cell carcinoma. (C and D) High expression of CIP2A in squamous cell carcinoma. (E and F) Low expression of CIP2A in adenocarcinoma. (G and H) High expression of CIP2A in adenocarcinoma. Abbreviation: CIP2A, cancerous inhibitor of protein phosphatase 2A.

Figure 3

Kaplan–Meier curves of OS based on CIP2A expression in NSCLC patients. Notes: (A) OS analysis of all patients. (B) OS analysis of squamous cell carcinoma patients. (C) OS analysis of adenocarcinoma patients. (D) OS analysis of patients who received postoperative chemotherapy. Abbreviations: CIP2A, cancerous inhibitor of protein phosphatase 2A; NSCLC, non-small cell lung cancer; OS, overall survival.