Prognostic value of long non-coding RNA CRNDE in gastrointestinal cancers: a meta-analysis

Figures & data

Table 1 Survival data of studies included

Author	Year	Country	Type	Source	Method	Cut-off	Sample size	Survival analysis	Analysis type	Follow-up months	HR availability	Quality score
Liu-148^Citation15	2016	China	CRC	Tissue	RT-qPCR	Youden index	148	OS	Multivariate	44.9 (mean)	Yes	8
Liu-142^Citation16	2016	China	CRC	Serum	RT-qPCR	Median	142	OS	Multivariate	55 (median)	Yes	8
Jiang^Citation11	2017	China	CRC	Tissue	RT-qPCR	Mean	251	OS	Multivariate	117 (total)	Yes	8
Du^Citation20	2017	China	GC	Tissue	RT-qPCR	Median	118	OS	Multivariate	60 (total)	Yes	8
Han^Citation17	2017	China	CRC	Tissue	RT-qPCR	Median	64	OS	Kaplan–Meier	50 (total)	Yes	8
Wang^Citation21	2017	China	PC	Tissue	RT-qPCR	N/A	58	OS	Kaplan–Meier	40 (total)	Yes	8
Ding^Citation18	2017	China	CRC	Tissue	RT-qPCR	X-tile algorithm	80	NA	NA	NA	No	6
Xia^Citation22	2018	China	ICC	Tissue	RT-qPCR	Mean	118	OS	Multivariate	60 (total)	Yes	8
Li^Citation19	2018	China	CRC	Serum	RT-qPCR	X-tile algorithm	74	OS	Kaplan-Meier	72 (total)	Yes	8

Abbreviations: CRC, colorectal cancer; GC, gastric cancer; PC, pancreatic cancer; ICC, intrahepatic cholangiocarcinoma; NA, none available.

Table 2 Clinicopathological features of studies included in the meta-analysis

Author	Year	Case number	LncRNA CRNDE expression
			High									Low
			Total	VA	M	LD	T3–4	LNM	DM	HTS	TS≥5	Total	VA	M	LD	T3–4	LNM	DM	HTS	TS≥5
Liu-148^Citation15	2016	148	104	NA	NA	NA	NA	NA	NA	NA	NA	44	NA	NA	NA	NA	NA	NA	NA	NA
Liu-142^Citation16	2016	142	71	NA	NA	NA	NA	NA	NA	NA	NA	71	NA	NA	NA	NA	NA	NA	NA	NA
Jiang^Citation11	2017	251	120	73	73	19	96	53	9	NA	77	131	65	77	37	96	42	2	NA	74
Du^Citation20	2017	118	61	34	21	39	40	35	NA	37	24	57	33	27	27	23	18	NA	21	18
Han^Citation17	2017	64	32	24	23	12	NA	24	7	NA	24	32	17	16	1	NA	13	5	NA	11
Wang^Citation21	2017	58	38	22	24	20	NA	26	NA	23	28	20	11	12	5	NA	6	NA	5	7
Ding^Citation18	2017	80	40	16	25	13	NA	NA	NA	23	25	40	21	20	19	NA	NA	NA	8	11
Xia^Citation22	2018	118	51	23	32	30	19	28	5	32	35	67	37	48	27	14	17	2	28	24
Li^Citation19	2018	74	8	5	4	NA	NA	NA	NA	NA	NA	66	42	48	NA	NA	NA	NA	NA	NA

Abbreviations: VA, venerable age, ≥50 y^11, ≥58 y^15, ≥60 y^16–22; M, male; LD, low differentiation; T3–4, depth of infiltration (T3–4); LNM, lymph node metastasis positive; DM, distant metastasis; HTS, high TNM stage (III–IV); T ≥5, tumor size ≥5 cm.

Figure 1 Flowchart of the current meta-analysis.

Figure 2 Meta-analysis of the pooled HRs of OS in different types of cancer with high CRNDE expression. (A) Forest plot of the correlation between CRNDE expression and OS. (B) Subgroup analysis of HRs of OS according to the factor of type of cancer. (C) Subgroup analysis of HRs of OS according to the factor of sample source.

Abbreviations: CRC, colorectal cancer; no-CRC, non-colorectal cancer; ES, effect size.

Table 3 Subgroup analysis of overall survival

Subgroups	Studies(n)	Number of patients	HR	95% CI	P	Heterogeneity
						I^2(%)	P	Model
Total	8	793	1.92	1.40–2.64	<0.001	61.5%	0.011	Random
Cancer type
CRC	5	679	2.12	1.59–2.84	<0.001	36.6%	0.177	Fixed
Non-CRC	3	294	1.34	1.19–1.51	0.024	45.2%	0.161	Fixed
Source
Tissue	6	757	1.62	1.26–2.09	<0.001	35.1%	0.173	Random
Serum	2	216	4.03	0.95–17.13	0.059	75.7%	0.043	Random
Sample size
≥100	5	777	1.80	1.32–2.46	<0.001	61.3%	0.035	Random
<100	3	196	2.56	0.84–7.78	0.098	65.9%	0.053	Random
Follow-up
<5	4	412	2.04	1.45–2.88	<0.001	0.0%	0.776	Random
≥5	4	561	2.02	1.21–3.39	0.008	76.1%	0.006	Random
Analysis type
Multivariate analysis	5	777	1.80	1.32–2.46	<0.001	61.3%	0.035	Random
Kaplan–Meier	3	196	2.56	0.84–7.78	0.098	65.9%	0.053	Random

Figure 3 Sensitivity of CRNDE expression for overall survival.

Table 4 Subgroup analysis of pooled odds ratios for the relationship between CRNDE expression levels and clinicopathological parameters by factor of cancer type

Category	Studies (n)	Number of patients	OR	95% CI	P	Heterogeneity
						I^2 (%)	P	Model
Age (venerable age vs no)	7	763	1.11	0.83–1.50	0.486	29.1%	0.206	Fixed
CRC	4	469	1.36	0.92–2.01	0.124	43.5%	0.151	Fixed
Non-CRC	3	294	0.84	0.52–1.33	0.451	0.0%	0.699	Fixed
Sex (female vs male)	7	763	1.00	0.74–1.36	0.997	29.5%	0.203	Fixed
CRC	4	469	0.79	0.54–1.77	0.240	24.9%	0.262	Fixed
Non-CRC	3	294	1.43	0.88–2.32	0.144	0.0%	0.608	Fixed
Differentiation (poor vs well-morderate)	5	609	2.03	0.79–5.20	0.140	81.2%	0.000	Random
CRC	2	315	2.56	0.07–92.17	0.140	90.6%	0.001	Random
Non-CRC	3	294	2.21	1.37–3.57	0.001	0.0%	0.756	Random
Depth of infiltration (T3–4 vs T1–2)	4	567	1.53	0.81–2.91	0.191	65.2%	0.035	Random
CRC	2	331	0.94	0.35–2.50	0.895	70.0%	0.068	Random
Non-CRC	2	236	2.54	1.46–4.41	0.001	0.0%	0.690	Random
Lymph node metastasis (positive vs negative)	5	609	2.82	1.85–4.31	p<0.001	29.7%	0.224	Random
CRC	2	315	2.41	0.97–6.01	0.059	60.5%	0.111	Random
Non-CRC	3	294	3.49	2.13–5.70	p<0.001	0.0%	0.740	Random
Distant metastasis (yes vs no)	3	433	2.72	1.16–6.35	0.021	0.0%	0.450	Fixed
CRC	2	315	2.49	0.93–6.64	0.069	32.0%	0.225	Fixed
Non-CRC	1	118	3.53	0.66–19.0	0.141	–	–	Fixed
TNM stage (III-IV vs I-II)	4	374	3.13	2.03–4.83	p<0.001	0.0%	0.508	Fixed
CRC	1	80	5.41	2.00–14.66	0.001	–	–	Fixed
Non-CRC	3	294	2.75	1.70–4.46	p<0.001	0.0%	0.642	Fixed
Tumor size (≥5 vs <5 cm)	6	689	2.81	1.62–4.88	p<0.001	62.5%	0.020	Random
CRC	3	395	2.99	1.13–7.93	p<0.001	75.8%	0.016	Random
Non-CRC	3	294	2.79	1.29–6.05	p<0.001	57.0%	0.098	Random

Figure 4 Forest plot of the correlation between CRNDE expression and clinicopathological characteristics. (A) Lymph node metastasis (positive vs negative). (B) Distant metastasis (yes vs no). (C) TNM stage (III–IV vs I–II). (D) Tumor size (≥5 vs <5 cm). (E) Depth of infiltration (T3–4 vs T1–2). (F) Differentiation (poor vs well-moderate).

Abbreviations: CRC, colorectal cancer; non, non-colorectal cancer; ES, effect size.

Table 5 The results of Begg’s and Egger’s tests for the publication bias

	Begg’s test		Duval and Tweedie’s trim and fill			Egger’s test
	Z	P	Trimmed studies	Observed values (CI)	Adjusted values (CI)	Intercept	P
HR analysis	0.870	0.386	5	1.92 (1.40–2.64)	1.33 (1.00–1.76)	1.734	0.013
Age	0.000	1.000	–	–	–	−0.652	0.685
Sex	0.300	0.764	–	–	–	−0.164	0.921
Differentiation	2.200	0.027	2	2.03 (0.79–5.20)	1.24 (0.52–2.97)	4.684	0.119
Depth of infiltration	0.340	0.734	–	–	–	−2.573	0.716
Lymph node metastasis	2.200	0.027	2	2.82 (1.85–4.31)	2.42 (1.63–3.58)	3.507	0.011
Distant metastasis	0.000	1.000	–	–	–	5.711	0.277
TNM stage	0.340	0.734	–	–	–	3.469	0.127
Tumor size	1.880	0.060	0	2.81 (1.62–4.88)	2.81 (1.62–4.88)	4.537	0.024

Figure S1 Meta-analysis of the pooled HRs of OS in different types of cancer with high CRNDE expression. (A) Subgroup analysis of HRs of OS according to the factor of sample size. (B) Subgroup analysis of HRs of OS according to the factor of follow-up time. (C) Subgroup analysis of HRs of OS according to the factor of analysis type.

Abbreviation: ES, effect size.

Figure S2 Forest plot of the correlation between CRNDE expression and clinicopathological characteristics. (A) Age (venerable age vs no). (B) Sex (female vs male).

Abbreviations: CRC, colorectal cancer; non, non-colorectal cancer; ES, effect size.

Figure S3 Sensitivity of CRNDE expression for the ORs of clinicopathological characteristics. (A) Age. (B) Sex. (C) Differentiation. (D) Depth of invasion. (E) Lymph node metastasis. (F) Distant metastasis. (G) TNM stage. (H) Tumor size.

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