Pooling analysis on prognostic value of PHH3 expression in cancer patients

Figures & data

Table 1 Main characteristics of all studies included in the meta-analysis

First author	Year	Patient source	Number of patient	Tumor types	Specimen	Method	PHH3 high expression (%)	Median (range) follow-up (month)	Outcome	M/U	HR (95% CI)	NOS
Kim et al^Citation15	2017	Korea	218	BC	Tissue	IHC	40.30	46	DFS	U	8.90 (1.07–74.0)	9
Chow et al^Citation13	2017	People’s Republic of China	55	USMT	Tissue	IHC	–	65.5	OS	M	2.71 (1.06–6.94)	7
Zhu et al^Citation8	2016	People’s Republic of China	61	Gliomas	Tissue	IHC	51.67	44.3	OS	M	1.19 (1.01–1.41)	8
Winther et al^Citation16	2016	Norway	160	Meningiomas	Tissue	IHC	–	–	RFS	M	3.05 (1.46–6.58)	7
Khan et al^Citation19	2016	India	101	GC	Tissue	IHC	58.42	–	OS DFS	U U	2.15 (1.07–4.28) 1.44 (0.61–3.41)	8
Goltz et al^Citation9	2015	Germany	637	PC	Tissue	IHC	–	51	RFS	U	1.84 (1.09–3.11)	8
Iwasaki et al^Citation21	2015	UK	27	MCC	Tissue	IHC	–	42	OS	M	7.47 (1.41–39.61)	6
Ramani et al^Citation22	2015	UK	80	Neuroblastomas	Tissue	IHC	30.00	121.3	OS	M	2.60 (1.10–5.80)	8
Alkhasawneh et al^Citation11	2015	USA	50	GSTS	Tissue	IHC	34.00	56.4	OS	U	0.97 (0.36–2.62)	7
Gerring et al^Citation24	2015	New Zealand	108	BC	Tissue	IHC	–	85	OS	M	4.35 (2.17–8.71)	7
Olar et al^Citation23	2015	USA	363	Meningiomas	Tissue	IHC	15.42	–	RFS	U	1.03 (1.02–1.05)	8
Duregon et al^Citation27	2014	Italy	48	AC	Tissue	IHC	–	40	OS	U	2.22(1.0–5.0)	6
Xu^Citation14	2014	China	52	PC	Tissue	IHC	94.23	–	OS	M	5.43 (1.24–23.80)	6
Klintman et al^Citation25	2013	Sweden	221	BC	Tissue	IHC	30.77	–	DFS	U	2.40 (1.40–4.30)	8
Gudlaugsson et al^Citation17	2013	Norway	237	BC	Tissue	IHC	35.44	–	RFS DFS	M M	10.6 (4.4–25.6) 8.9 (3.4–23.5)	8
Ladstein et al^Citation18	2012	Norway	338	CNM	Tissue	IHC	74.85	61.5	OS	M	1.90 (1.04–3.36)	9
Brunner et al^Citation26	2012	Australia	99	EC	Tissue	IHC	48.48	72	OS	M	5.9 (1.7–31.4)	8
Gudlaugsson et al^Citation10	2011	Norway	240	BC	Tissue	IHC	35.00	117	OS	M	9.6 (3.1–29.9)	9
Kim et al^Citation20	2007	Germany	99	Meningiomas	Tissue	IHC	–	42	RFS	M	1.07 (1.06–1.10)	8

Note:

‘–’ unobtainable data.

Abbreviations: AC, adrenocortical carcinoma; BC, breast cancer; CNM, cutaneous nodular melanoma; DFS, disease-free survival; EC, endometrial carcinoma; GC, gastric cancer; GSTS, gastrointestinal stromal tumors; IHC, immunohistochemistry; M, multivariate; MCC, Merkel cell carcinoma; NOS, Newcastle–Ottawa scale; OS, overall survival; PC, prostate carcinoma; PHH3, phospho-histone-H3; RFS, recurrence-free survival; U, univariate; USMT, uterine smooth muscle tumor.

Figure 1 Flow diagram of the study selection process.

Table 2 Main meta-analysis results

Analysis	No. of studies	No. of patients	Model	HR (95% CI)	P-value	Heterogeneity		Publication bias
						I^Citation2 (%)	P-value	Begg’s P	Egger’s P
OS	12	1259	Random	2.66 (1.74–4.08)	0.000	74.5	0.000	0.047	0.000
Tumor type	–	–	–	–	–	–	–	–	–
Nervous system tumor	2	141	Random	1.58 (0.76–3.28)	0.226	69.4	0.071	–	–
Digestive system tumor	2	151	Random	1.57 (0.73–3.35)	0.247	39.4	0.199	–	–
Cutaneous tumor	2	365	Random	2.99 (0.85–10.56)	0.089	56.6	0.129	–	–
Breast cancer	2	348	Random	5.66 (2.72–11.78)	0.000	26.7	0.243	–	–
Urogenital tumor	4	254	Random	3.01 (1.78–5.09)	0.000	0.00	0.567	–	–
Ethnicity	–	–	–	–	–	–	–	–	–
Asian	4	269	Random	1.98(1.08–3.63)	0.026	66.6	–	–	–
Caucasian	8	990	Random	3.01(1.87–4.85)	0.000	51.0	–	–	–
HR estimate	–	–	–	–	–	–	–	–	–
Multivariate analysis	7	1033	Random	3.17 (1.66–6.04)	0.000	81.8	0.000	–	–
Univariate analysis	5	226	Random	1.93 (1.31–2.82)	0.001	74.5	0.000	–	–
DFS	4	777	Random	3.40 (1.47–7.87)	0.004	67.4	0.027	–	–
RFS	5	1496	Random	2.80 (1.61–4.85)	0.000	72.6	0.006	–	–

Note

‘–’ unobtainable data.

Abbreviations: DFS, disease-free survival; OS, overall survival; RFS, recurrence-free survival.

Figure 2 Forest plot of HR for the association of PHH3 expression and OS.

Note: Weights are from random effects analysis.

Abbreviations: PHH3, phospho-histone-H3; OS, overall survival.

Figure 3 Forest plot of HR for the association of PHH3 expression and DFS.

Note: Weights are from random effects analysis.

Abbreviations: DFS, disease-free survival; PHH3, phospho-histone-H3.

Figure 4 Forest plot of HR for the association of PHH3 expression and RFS.

Note: Weights are from random effects analysis.

Abbreviations: PHH3, phospho-histone-H3; RFS, recurrence-free survival.

Figure 5 Sensitivity analysis of pooled HRs on the association between PHH3 expression and OS.

Abbreviations: OS, overall survival; PHH3, phospho-histone-H3.

Figure 6 Funnel plots of publication bias for all of the included studies reported with OS.

Abbreviations: Iog[HR], logarithm hazard ratio; OS, overall survival; s.e., standard error.

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