NANOG as an adverse predictive marker in advanced non–small cell lung cancer treated with platinum-based chemotherapy

Figures & data

Table 1 The clinical characteristics of patients according to low and high NANOG expression

Variables	No of patients (%)	NANOG expression		p-value
		Low (<180)	High (≥180)
Total number of patients	112 (100)	68 (60)	44 (40)
Gender				0.419
Female	34 (30)	19 (28)	15 (34)
Male	78 (70)	49 (72)	29 (66)
Age				0.852
<65 years	41 (37)	25 (37)	16 (36)
≥65 years	71 (63)	43 (63)	28 (64)
Smoking				0.764
Never	37 (33)	22 (32)	15 (34)
Ever	75 (67)	46 (68)	29 (66)
ECOG performance				0.682
0, 1	79 (71)	47 (69)	32 (73)
≥2	33 (29)	21 (31)	12 (27)
T stage				0.637
T1	7 (6)	4 (6)	3 (7)
≥T2	105 (94)	64 (94)	34 (93)
N stage				>0.999
N0	11 (10)	7 (10)	4 (9)
≥N1	101 (90)	61 (90)	40 (91)
Stage				0.645
IIIB	23 (21)	13 (19)	10 (23)
IV	89 (79)	55 (81)	34 (77)
EGFR mutation*				>0.999
Positive	8 (40)	5 (38)	3 (43)
Negative	12 (60)	8 (62)	4 (57)
Differentiation				0.487
Well	83 (74)	52 (76)	31 (70)
Moderate–poor	29 (26)	16 (24)	13 (30)
Tumor histology				0.716
ADC	64 (57)	45 (66)	19 (43)
SQCC	48 (43)	23 (34)	25 (57)
First-line treatment				0.743
Pemetrexed/platinum	37 (33)	23 (34)	14 (32)
Gemcitabine/platinum	49 (44)	27 (40)	22 (50)
Paclitaxel/platinum	15 (13)	10 (15)	5 (11)
Docetaxel/platinum	11 (10)	8 (11)	3 (7)

Note:

* EGFR mutation data were available in 20 adenocarcinoma patients.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; N, lymph node; T, tumor; ADC, adenocarcinoma; SQCC, squamous cell carcinoma.

Figure 1 Representative immunohistochemical staining sections for NANOG with different histologic scores (H-scores) (×200).

Notes: NANOG was primarily detected in the cytoplasm of adenocarcinoma and squamous cell carcinoma cells, and a few were detected inside the nucleus. (A) H-score of 50; (B) H-score of 150; (C) H-score of 250.
Abbreviations: ADC, adenocarcinoma; SQCC, squamous cell carcinoma.

Figure 2 Distribution of H-scores.

Notes: Median H-scores of all patients, patients with adenocarcinoma, and patients with squamous cell carcinoma were 178.3, 167.1, and 189.4, respectively. Bars denote median and interquartile range.
Abbreviations: ADC, adenocarcinoma; SQCC, squamous cell carcinoma.

Figure 3 Kaplan–Meier survival curves for progression-free survival (A) and overall survival (B) in all patients. p-values were determined using the log-rank test.

Abbreviations: OS, overall survival; PFS, progression-free survival.

Table 2 Survival analyses results according to clinical parameters in all study subjects

Variables	No of patients (%)	Progression-free survival (PFS)			Overall survival (OS)
		Median PFS (months)	Univariate analysis, p-value	Multivariate analysis adjusted HR (95% CI)	Median OS (months)	Univariate analysis, p-value	Multivariate analysis adjusted HR (95% CI)
Total number of patients	112 (100)	6.5			12.8
Gender			0.154	NA		0.677	NA
Female	34 (30)	7.1			13.0
Male	78 (70)	4.6			12.5
Age			0.216	NA		0.081
<65 years	41 (37)	8.2			14.5		Reference
≥65 years	71 (63)	5.6			11.2		1.18 (1.06–2.14)
Smoking			0.513	NA		0.125	NA
Never	37 (33)	5.8			15.1		Reference
Ever	75 (67)	7.3			12.4		1.59 (0.26–2.07)
ECOG performance			0.082			0.002
0, 1	79 (71)	7.5		Reference	14.7		Reference
≥2	33 (29)	4.4		1.34 (0.87–2.07)	8.9		2.42 (1.47–3.99)
T stage			0.026			0.824	NA
T1	7 (6)	9.2		Reference	14.1
≥T2	105 (94)	5.5		2.14 (0.94–9.53)	13.0
N stage			0.314	NA		0.793	NA
N0	11 (10)	8.0			13.1
≥N1	101 (90)	6.1			12.2
Stage			0.013			0.019
IIIB	23 (21)	8.1		Reference	15.3		Reference
IV	89 (79)	4.3		2.06 (1.23–3.48)	11.2		1.84 (1.16–3.10)
Differentiation			0.313	NA		0.527	NA
Well	83 (74)	7.3			13.1
Moderate–poor	29 (26)	5.4			10.9
Tumor histology			0.034			0.361	NA
ADC	64 (57)	8.5		Reference	14.5
SQCC	48 (43)	4.2		2.10 (1.31–3.37)	8.7
NANOG expression			<0.001			<0.001
Low	68 (60)	8.1		Reference	16.5		Reference
High	44 (40)	3.6		3.09 (2.01–4.76)	8.7		3.00 (1.98–4.54)

Abbreviations: ECOG, Eastern Cooperative Oncology Group; N, lymph node; T, tumor; ADC, adenocarcinoma; NA, not analyzed; SQCC, squamous cell carcinoma.

Figure 4 Kaplan–Meier survival curves for progression-free survival (A) and overall survival (B) in patients with adenocarcinoma. p-values were determined using the log-rank test.

Abbreviations: OS, overall survival; PFS, progression-free survival.

Figure 5 Kaplan–Meier survival curves for progression-free survival (A) and overall survival (B) in patients with squamous cell carcinoma. p-values were determined using the log-rank test.

Abbreviations: OS, overall survival; PFS, progression-free survival.