The association between osteopontin and survival in non-small-cell lung cancer patients: a meta-analysis of 13 cohorts

Figures & data

Table 1 Newcastle–Ottawa quality assessment scale for cohort studies

Selection

1) Representativeness of the exposed cohort

a) Truly representative of the average NSCLC patients (describe) in the community (*)

b) Somewhat representative of the average NSCLC patients in the community (*)

c) Selected group of users, eg, nurses, volunteers

d) No description of the derivation of the cohort

2) Selection of the nonexposed cohort

a) Drawn from the same community as the exposed cohort (*)

b) Drawn from a different source

c) No description of the derivation of the nonexposed cohort

3) Ascertainment of exposure (proof of NSCLC and osteopontin measurement)

a) Secure record (eg, surgical records) (*)

b) Structured interview (*)

c) Written self-report

d) No description

4) Demonstration that outcome of interest was not present at start of study

a) Yes (*)

b) No

Comparability

1) Comparability of cohorts on the basis of the design or analysis

a) Study controls for recurrence or metastasis (select the most important factor) (*)

b) Study controls for any additional factor (age, stage, grade, cirrhosis, etc) (*)

Outcome

1) Assessment of outcome

a) Independent blind assessment (*)

b) Record linkage (*)

c) Self-report

d) No description

2) Was follow-up long enough for outcomes to occur

a) Yes (2 years) (*)

b) No

3) Adequacy of follow-up of cohorts

a) Complete follow-up – all subjects accounted for (*)

b) Subjects lost to follow-up unlikely to introduce bias – small number lost >25% (select an adequate%) follow-up, or description provided of those lost) (*)

c) Follow-up rate <75% (select an adequate%) and no description of those lost

d) No statement

Notes: A study can be awarded a maximum of one star for each numbered item within the selection and outcome categories. A maximum of two stars can be given for comparability.

Abbreviation: NSCLC, non-small-cell lung cancer.

Figure 1 Flow diagram of the study selection process.

Abbreviations: OPN, osteopontin; NSCLC, non-small-cell lung cancer.

Table 2 Characteristics of studies included in the meta-analysis

Study	Year	Study design	Sample size, n (M/F)	Country	Tumor stagea (I–II/III–IV, n)	Follow-up (months)	Sample	Osteopontin detection method	Survival analysis	Hazard ratio estimated	Adjusted factors	NOS scoresb
Chambers et al^Citation18	1996	Prospective	25 (17/8)	England	20/5	34	Tumor tissue	IHC	OS	UV		6/9
Schneider et al^Citation10	2004	Prospective	82 (63/19)	America	58/24	86	Tumor tissue	PCR	OS	UV		5/9
Donati et al^Citation7	2005	Retrospective	163	Italy	NR	49	Tumor tissue	IHC	OS and DFS	MV	NR	6/9
Mack et al^Citation21	2008	Prospective	156	America	NR	NR	Plasma	ELISA	OS and DFS	UV		5/9
Isa et al^Citation12	2009	Prospective	67 (46/21)	Japan	0/67	NR	Serum	ELISA	OS and DFS	UV		6/9
Zhang et al^Citation20	2010	Retrospective	180 (136/44)	People’s Republic of China	110/70	25	Tumor tissue	IHC	DFS	MV	Sex, histopathological type, T staging, N staging, and BSP expression	5/9
Rud et al^Citation19	2013	Prospective	191	Norway	NR	37	Tumor tissue	IHC	OS and DFS	MV	Age, sex, pT category, pN category, and tumor differentiation and histology	6/9
Sun et al^Citation17	2013	Retrospective	159 (109/50)	People’s Republic of China	95/64	46	Tumor tissue	IHC	OS and DFS	UV		5/9
Takenaka et al^Citation13	2013	Prospective	244 (166/78)	Japan	189/55	48	Serum	ELISA	OS	MV	Sex, smoking, histology, T factor, and N factor	7/9
Ostheimer et al^Citation24	2014	Prospective	55 (47/8)	Germany	3/52	37	Plasma	ELISA	OS	UV		7/9
Han et al^Citation23	2013	Prospective	53 (47/6)	Korea	7/46	30	Plasma	ELISA	OS	UV		7/9
Yan et al^Citation25	2015	Prospective	163 (104/59)	People’s Republic of China	86/77	50	Tumor tissue	IHC	OS and DFS	MV	Lymph node staging and TNM stage	7/9
Zhang et al^Citation22	2014	Retrospective	92 (53/39)	People’s Republic of China	0/92	NR	Tumor tissue	IHC	OS and DFS	MV	Sex, age, pathological type, metastasis and chemotherapy regimens, and grade of differentiation	6/9

Notes:

a Tumor stage was classified according to International Union Against Cancer (UICC, sixth edition).

b Study quality is listed using the results of the Newcastle–Ottawa questionnaire.

Abbreviations: M, male; F, female; NOS, Newcastle–Ottawa Scale; IHC, immunohistochemistry; OS, overall survival; PCR, polymerase chain reaction; DFS, disease-free survival; NR, not reported; ELISA, enzyme-linked immunosorbent assay; MV, multivariate analysis; UV, univariate analysis.

Figure 2 Meta-analysis of the association between OPN overexpression and OS of NSCLC.

Notes: The summary HR and 95% CIs were also shown (according to the random-effect estimations). Weights are from random-effects analysis.
Abbreviations: OPN, osteopontin; OS, overall survival; NSCLC, non-small-cell lung cancer; HR, hazard ratio; CI, confidence interval.

Table 3 Subgroup analysis of the OPN levels in NSCLC patients

Outcome	Variable	N	Model	HR (95% CI)	P-value	I^2 (%)	Pheterogeneity
OS	All	12	Random	2.20 (1.71, 2.83)	<0.001	69.6	<0.001
	Area
	Non-Asia	6	Fixed	1.66 (1.43, 1.93)	<0.001	0.0	0.562
	Asia	6	Random	2.68 (1.63, 4.43)	<0.001	79.4	<0.001
	Method
	ELISA	5	Fixed	1.80 (1.43, 2.27)	<0.001	0.0	0.840
	IHC	6	Random	2.63 (1.65, 4.22)	<0.001	84.1	<0.001
	PCR	1		1.93 (1.24, 3.01)
	Sample type
	Tumor tissue	7	Random	2.50 (1.68, 3.73)	<0.001	81.4	<0.001
	Plasma	3	Fixed	1.71 (1.28, 2.28)	<0.001	0.0	0.724
	Serum	2	Fixed	1.98 (1.35, 2.92)	0.001	0.0	0.521
DFS	All	8	Random	2.11 (1.62, 2.74)	<0.001	50.3	0.050
	Area
	Non-Asia	3	Fixed	1.74 (1.10, 2.76)	0.017	44.4	0.166
	Asia	5	Fixed	2.40 (1.86, 3.09)	<0.001	20.3	0.285
	Method
	ELISA	2	Random	1.79 (1.11, 2.86)	0.016	59.8	0.115
	IHC	6	Fixed	2.36 (1.89, 2.96)	<0.001	37.2	0.158
	Sample type
	Tumor tissue	6	Fixed	2.36 (1.89, 2.96)	<0.001	37.2	0.158
	Plasma	1		1.46 (1.05, 2.00)
	Serum	1		2.38 (1.43, 4.00)

Abbreviations: OPN, osteopontin; NSCLC, non-small-cell lung cancer; HR, hazard ratio; CI, confidence interval; OS, overall survival; ELISA, enzyme-linked immunosorbent assay; IHC, immunohistochemistry; PCR, polymerase chain reaction; DFS, disease-free survival.

Figure 3 Meta-analysis of the association between OPN overexpression and DFS of NSCLC.

Notes: The summary HR and 95% CIs were also shown (according to the random-effect estimations). Weights are from random-effects analysis.
Abbreviations: OPN, osteopontin; NSCLC, non-small-cell lung cancer; DFS, disease-free survival; HR, hazard ratio; CI, confidence interval.

Figure 4 Meta-analysis of the association between OPN overexpression and tumor TNM stage of NSCLC.

Note: The summary OR and 95% CIs were also shown (according to the fixed-effect estimations).
Abbreviations: OPN, osteopontin; NSCLC, non-small-cell lung cancer; OR, odds ratio; CI, confidence interval.

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