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

Figures & data

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.

Table 1 Clinicopathological variables of patient samples and expression of CIP2A in NSCLC

Variables	Patients (n)	CIP2A low (%)	CIP2A high (%)	χ^2	p-value
Age (years)				1.006	0.361
≤58	107	62 (57.9)	45 (42.1)
>58	102	66 (64.7)	36 (35.3)
Gender				0.031	0.860
Male	156	95 (60.9)	61 (39.1)
Female	53	33 (62.3)	20 (37.7)
Smoking history				0.864	0.353
Yes	132	84 (63.6)	48 (36.4)
No	77	44 (57.1)	33 (42.9)
Pathologic stage				15.642	0.000*
I	59	48 (81.4)	11 (18.6)
II	81	47 (58.0)	34 (42.0)
III	69	33 (47.8)	36 (52.2)
T stage				1.578	0.454
T1	39	23 (59.0)	16 (41.0)
T2	148	94 (63.5)	54 (36.5)
T3 + T4	22	11 (50.0)	11 (50.0)
N stage				14.332	0.001*
N0	104	77 (74.0)	27 (26.0)
N1	40	20 (58.0)	20 (42.0)
N2	65	31 (47.8)	34 (52.2)
Histological type				1.334	0.248
Squamous cell carcinoma	116	67 (57.8)	49 (42.2)
Adenocarcinoma	93	61 (65.6)	32 (34.4)
Differentiation grade				4.914	0.086
Well	27	14 (51.9)	13 (48.1)
Moderate	90	50 (55.6)	40 (44.4)
Poor	92	64 (69.6)	28 (30.4)

Note:

* Significant difference.

Abbreviations: CIP2A, cancerous inhibitor of protein phosphatase 2A; NSCLC, non-small cell lung cancer.

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.

Table 2 Univariate and multivariate analyses of the prognostic factors in 209 patients with NSCLC

Variables	Patients (n)	Univariate		Multivariate
		Median survival time (months) (95% CI)	p-valuea	HR (95% CI)	p-valueb
Age (years)			0.234
≤58	107	50.0 (23.3–76.7)
>58	102	50.0 (34.8–65.2)
Gender			0.574
Male	156	44.0 (24.9–63.1)
Female	53	54.0 (43.3–64.7)
Smoking history			0.337
Yes	132	39.0 (23.2–54.8)
No	77	59.0 (46.6–71.4)
Pathologic stage			0.005*
I	59	75.0 (53.5–96.5)
II	81	59.0 (34.5–83.5)
III	69	31.0 (25.9–36.1)
N stage			0.001*	1.441 (1.134–1.830)	0.003*
N0	104	75.0 (56.6–93.4)
N1	40	44.0 (13.0–75.0)
N2	65	30.0 (25.1–34.9)
T stage			0.068	1.749 (1.264–2.421)	0.001*
T1	39	68.0 (–)c
T2	148	49.0 (31.8–66.2)
T3 + T4	22	21.0 (6.1–35.9)
Histological type			0.003*	1.949 (1.384–2.746)	,0.001*
Squamous cell carcinoma	116	61.0 (32.0–90.0)
Adenocarcinoma	63	39.0 (24.0–54.0)
Differentiation grade			0.975
Well	27	57.0 (27.7–86.3)
Moderate	90	49.0 (30.4–67.6)
Poor	92	50.0 (26.5–73.5)
CIP2A expression			0.005*	1.616 (1.137–2.298)	0.005*
Low	128	68.0 (48.2–87.8)
High	81	31.0 (23.8–38.2)
Chemotherapy			0.037*	2.543 (1.703–3.799)	0.000*
Yes	151	57.0 (37.9–76.1)
No	58	24.0 (16.5–31.5)
Radiotherapy			0.006*	1.304 (0.845–2.011)	0.230
Yes	58	30.0 (22.5–37.5)
No	151	64.0 (49.1–78.9)

Notes:

a Log-rank test.

b Cox regression test.

c Because of the relative high percentage (46.2%) of censored data in T1 group, the SPSS software didn’t show the 95% CI.

* Significant difference.

Abbreviations: CI, confidence interval; CIP2A, cancerous inhibitor of protein phosphatase 2A; HR, hazard ratio; NSCLC, non-small cell lung cancer.

Table 3 Multivariate analysis of the prognostic factors using Cox regression test in 151 NSCLC patients who received postoperative chemotherapy

Variable	HR	95% CI	p-value
T stage	1.387	0.945–2.036	0.095
N stage	1.336	1.023–1.747	0.034*
Histological type	2.039	1.353–3.072	0.001*
CIP2A expression	1.720	1.148–2.577	0.009*
Radiotherapy	1.356	0.844–2.181	0.208

Note:

* Significant difference.

Abbreviations: CI, confidence interval; CIP2A, cancerous inhibitor of protein phosphatase 2A; HR, hazard ratio; NSCLC, non-small cell lung cancer.