High-Expression of Cytoplasmic Poly (A) Binding Protein 1 (PABPC1) as a Prognostic Biomarker for Early-Stage Esophageal Squamous Cell Carcinoma

Figures & data

Table 1 Clinicopathologic Parameters of the 231 ESCC Patients

Variable	Total	Man	Woman	P
Age (y), median (range)	61.0 (43–79) n=231	60.7 (43–79) n=200	62.7 (47–78) n=31	0.169
Smoking, >5/day (%)	79/134 (59.0)	78/117 (66.7)	1/17 (5.9)	<0.001**
Alcohol, >25 g/day (%)	78/133 (58.6)	76/116 (65.5)	2/17 (11.8)	<0.001**
Tumor site, U/M/L (%)	18/99/99 (8.3/45.8/45.8) n=216	14/82/93 (7.4/43.4/49.2) n=189	4/17/6 (14.8/63.0/22.2) n=27	0.026*
Tumor size, median (range)	3.9 (1.1–15.0) n=231	4.0 (1.1–8.5) n=200	3.9 (1.5–15.0) n=31	0.765
DTCD, well/moderate/low (%)	18/110/103 (7.8/47.6/44.6) n=231	16/94/90 (8/47/45) n=200	2/16/13 (6.5/51.6/41.9) n=31	0.879
LN
No. of LNs diagnosed, median (range)	16.1 (1–54) n=231	16.6 (1–54) n=200	12.9 (4–28) n=31	0.620
No. of LNs metastasized, median (range)	1.48 (0–21) n=231	1.54 (0–21) n=200	1.06 (0–6) n=31	0.974
Pathological type, ME/UT/MU/CT (%)	44/153/19/8 (19.6/68.3/21.9/3.6)	38/134/13/8 (19.7/69.4/6.7/4.1)	6/19/6/0 (19.4/61.3/19.4/0)	0.087
	n=224	n=193	n=31
Pathological stage, I/II/III/IV (%)	33/79/106/11 (14.4/34.5/46.3/4.8) n=229	28/65/95/10 (14.4/32.8/48/5.1) n=198	5/14/11/1 (16.1/45.2/35.5/3.2) n=31	0.506
Immunohistochemistry
Ki-67, positivity (%)	231/231 (100)	200/200 (100)	31/31 (100)	1.000
p53, positivity (%)	121/231 (52.4)	105/200 (52.5)	16/31 (51.6)	0.927
Nm23, positivity (%)	140/231 (60.6)	120/200 (60)	20/31 (64.5)	0.632
PABPC1, positivity (%)	179/231 (77.5)	154/200 (77)	25/31 (80.6)	0.833
Follow-up month
Duration, median (range)	37.9 (1–93) n=152	37.9 (1–93) n=131	38.5 (1–91) n=21	0.932
Outcome, death (%)	99/152 (65.1)	86/131 (65.6)	13/21 (61.9)	0.738
Recurrence (%)	81/139 (58.3)	70/119 (58.8)	11/20 (55)	0.748

Notes: Continuous variables were analyzed using the Student’s t test, and categorical variables were analyzed using the χ² test. The data of the variables was based on the 231 patients, except “follow-up duration”, “outcome” and “recurrence”. Significance analysis was two-tailed, and p<0.05 was considered statistically significant. * at p<0.05 level, ** at p<0.01 level.

Abbreviations: ESCC, esophageal squamous cell carcinoma; U, upper esophagus; M, middle esophagus; L, lower esophagus; LN, lymph node; DTCD, degree of tumor cell differentiation; ME, medullary type; UT, ulcerative type; MU, mushroom type; CT, constrictive type.

Figure 1 The mRNA expression level of PABPC1 in ESCC.

Notes: The mRNA expression levels of PABPC1 in total ESCC and their paired adjacent normal tissues (control) (A); the mRNA expression level of PABPC1 was increased in ESCC with high PABPC1 expression, but decreased in ESCC with low PABPC1 expression, compared to that of the control (B). Student’s t test was used for significance analysis (two-tailed), and p<0.05 was considered statistically significant. Abbreviation: ESCC, esophageal squamous cell carcinoma.

Table 2 Relationship Analyses Among PABPC1 Expression and Clinicopathologic Parameters in ESCC Tissues

	Age	Gender	Smoking	Alcohol	Tumor Site	Tumor Size	DTCD	LNM	Pathological Type	Pathological Stage	Ki-67 PP	p53 PP	nm23 PP	PABPC1 PP	Outcome (Death)	Tumor Recurrence
Age	\	0.091	−0.139	0.009	−0.054	−0.166 *	0.004	−0.13	−0.055	−0.051	0.035	0.113	−0.093	0.102	0.072	−0.052
Gender	0.091	\	−0.365**	−0.361**	−0.179**	−0.02	0.008	−0.116	0.025	−0.07	0.106	0.024	0.112	0.061	−0.010	−0.024
Smoking	−0.139	−0.365**	\	0.729**	0.01	0.045	−0.061	0.107	0.084	−0.026	−0.083	−0.18 *	−0.067	−0.045	0.055	0.014
Alcohol	0.009	−0.361**	0.729**	\	−0.043	0.005	−0.121	0.12	0.096	−0.009	−0.062	−0.066	−0.086	−0.105	0.206 *	0.14
Tumor site	−0.054	−0.179**	0.010	−0.043	\	0.197**	0.004	0.1	0	0.088	0.025	0.081	0.007	−0.075	−0.075	−0.061
Tumor size	−0.166 *	−0.020	0.045	0.005	0.197**	\	0.111	0.198**	0.007	0.241**	0.112	0.145 *	−0.005	−0.049	0.072	0.174 *
DTCD	0.004	0.008	−0.061	−0.121	0.004	0.111	\	0.273**	−0.026	0.313**	0.215**	0.113	−0.0.103	0.124	0.152	0.204 *
LNM	−0.13	−0.116	0.107	0.12	0.1	0.198**	0.273**	1	0.034	0.822**	0.139 *	0.061	−0.165 *	0.166 *	0.481**	0.499**
Pathological type	−0.055	0.025	0.084	0.096	0	0.007	−0.026	0.034	\	0.039	0.041	0.080	−0.013	0.076	0.007	−0.030
Pathological stage	−0.051	−0.070	−0.026	−0.009	0.088	0.241**	0.313**	0.822**	0.039	\	0.105	0.108	−0.139 *	0.136 *	0.504**	0.514**
Ki-67 PP	0.035	0.106	−0.083	−0.062	0.025	0.112	0.215**	0.139 *	0.041	0.105	\	−0.008	0.050	0.025	0.033	0.064
p53 PP	0.113	0.024	−0.18 *	−0.066	0.081	0.145 *	0.113	0.061	0.08	0.108	−0.008	\	−0.133 *	0.001	0.017	−0.041
nm23 PP	−0.093	0.112	−0.067	−0.086	0.007	−0.005	−0.0.103	−0.165 *	−0.013	−0.139 *	0.05	−0.133 *	\	−0.076	−0.100	−0.087
PABPC1 PP	0.102	0.061	−0.045	−0.105	−0.075	−0.049	0.124	0.166 *	0.076	0.136 *	0.025	0.001	−0.076	\	0.384**	0.337**
Outcome (death)	0.072	−0.010	0.055	0.206 *	−0.075	0.072	0.152	0.481**	0.007	0.504**	0.033	0.017	−0.100	0.384**	\	0.747**
Tumor recurrence	−0.052	−0.024	0.014	0.14	−0.061	0.174 *	0.204 *	0.499**	−0.03	0.514**	0.064	−0.041	−0.087	0.337**	0.747**	\

Notes: Correlation between the parameters except “outcome” and “tumor recurrence” was based on the data from all the 231 patients. * at p<0.05 level, ** at p<0.01 level.

Abbreviations: ESCC, esophageal squamous cell carcinoma; DTCD, degree of tumor cell differentiation; LNM, lymph node metastasis; PP, percentage of positive tumor cells relative to the total number of tumor cells.

Figure 2 Immunohistochemical staining of PABPC1 in ESCC.

Notes: Representative images of PABPC1 staining with low expression (A, C) and high expression (E) in ESCC tissues and their paired adjacent normal epithelium tissues (B,D, F, respectively). Abbreviation: ESCC, esophageal squamous cell carcinoma.

Figure 3 Ki-67, p53, nm23, and PABPC1 in the outcome prediction of the patient with ESCC.

Notes: Kaplan-Meier analyses revealed that high expression of PABPC1 was correlated with poor OS in total ESCC specimens (A); expression of Ki-67, p53, and nm23 was not correlated with poor OS in total ESCC specimens (B-D); high expression of PABPC1 was correlated with poor OS in early-staged (pStage-I,-II) ESCC specimens (E) and advanced (pStage-III, -IV) ESCC specimens (I); expression of Ki-67, p53, and nm23 was not correlated with poor OS in early-staged (pStage-I,-II) ESCC specimens (F, G, H, respectively) or advanced (pStage-III, -IV) ESCC specimens (J, K, L, respectively). Abbreviations: ESCC, esophageal squamous cell carcinoma; OS, overall survival.

Table 3 Analysis of Prognostic Factors Using Univariate and Multivariate Analyses Among the 152 Followed-Up ESCC Patients

Variable	Univariate		Multivariate
	HR (95% CI)	P	HR (95% CI)	P
Age (y), >60	1.058 (0.711–1.574)	0.781
Gender, man	0.947 (0.528–1.697)	0.854
Smoking, >5/day	1.058 (0.703–1.592)	0.788
Alcohol, >25 g/day	1.320 (0.878–1.985)	0.182
Tumor site, U	1		1
M	0.351 (0.163–0.758)	0.008**	0.301 (0.13–0.696)	0.005**
L	0.380 (0.176–0.82)	0.014*	0.264 (0.114–0.611)	0.002**
Tumor size, ≤3 cm	1
3–5 cm	1.260 (0.823–1.929)	0.287
>5 cm	1.333 (0.614–2.893)	0.467
DTCD, Well	1		1
Moderate	1.338 (0.88–2.033)	0.173	0.964 (0.471–1.974)	0.483
Low	2.535 (1.247–5.156)	0.010*	1.002 (0.499–2.011)	0.737
No. of LNs metastasized, 0	1		1
1–2	3.274 (2.052–5.223)	<0.001**	1.664 (0.784–3.532)	0.185
≥3	4.637 (2.688–7.999)	<0.001**	2.593 (1.038–6.476)	0.041*
Pathological type, ME	1
UT	1.566 (0.898–2.732)	0.114
MU	1.282 (0.466–3.531)	0.63
CT	0.608 (0.139–2.661)	0.509
Pathological stage, I	1		1
II	1.582 (0.681–3.675)	0.286	1.272 (0.53–3.049)	0.590
III	5.591 (2.389–13.085)	<0.001**	2.235 (0.79–6.324)	0.130
IV	7.934 (2.216–28.403)	0.001**	3.645 (0.847–15.678)	0.082
Ki-67, 0–25%	1
25–50%	0.952 (0.537–1.685)	0.865
>50%	1.040 (0.579–1.867)	0.895
P53, 0–25%	1
25–50	0.642 (0.294–1.398)	0.264
50–75	1.294 (0.665–2.518)	0.448
>75%	0.848 (0.484–1.487)	0.565
nm23, 0–25%	1
25–50%	0.945 (0.557–1.602)	0.833
50–75%	0.748 (0.382–1.467)	0.398
>75%	0.625 (0.341–1.144)	0.127
PABPC1, low expression	1		1
PABPC1, high expression	3.178 (2.092–4.829)	<0.001**	2.622 (1.68–4.129)	<0.001**

Notes: Significance analysis was two-tailed, and p<0.05 was considered statistically significant. * at p<0.05 level, ** at p<0.01 level.

Abbreviations: ESCC, esophageal squamous cell carcinoma; U, upper esophagus; M, middle esophagus; L, lower esophagus; DTCD, degree of tumor cell differentiation; LN, lymph node; ME, medullary type; UT, ulcerative type; MU, mushroom type; CT, constrictive type.