Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

Figures & data

Table 1 Characteristics of the GEO datasets included in the meta-analysis

Series	Country	Year	Platform	Sample source	PC patients	Normal tissues
GSE14245	USA	2008	GPL570	Saliva	12	12
GSE11838	USA	2008	GPL6977	Tissue	28	79
GSE15471	Romania	2009	GPL570	Tissue	39	39
GSE16515	USA	2009	GPL570	Tissue	36	16
GSE22780	USA	2011	GPL570	Tissue	8	8
GSE32676	USA	2011	GPL570	Tissue	25	7
GSE18670	Belgium	2012	GPL570	Tissue/peripheral blood	6	6
GSE15932	People’s Republic of China	2012	GPL570	Peripheral blood	16	8
GSE28735	USA	2012	GPL6244	Tissue	45	45
GSE23397	Germany	2013	GPL5188	Tissue	15	6
GSE41368	Italy	2013	GPL6244	Tissue	6	6
GSE43795	South Korea	2013	GPL10558	Tissue	26	5
GSE49641	Spain	2013	GPL6244	Peripheral blood	18	18
GSE43288	UK	2013	GPL96/GPL97	Tissue	4	3
GSE27890	USA	2014	GPL570	Tissue	4	4
GSE56560	UK	2014	GPL5175	Tissue	28	7
GSE58561	Norway	2014	GPL14550	Tissue	3	2
GSE55643	UK	2014	GPL6480	Tissue	45	8
GSE60979	Norway	2015	GPL14550	Tissue	49	12
GSE71008	USA	2015	GPL9052	Plasma	6	50
GSE74629	Spain	2015	GPL10558	Peripheral blood	36	14
GSE71989	USA	2015	GPL570	Tissue	14	8
GSE62165	Belgium	2016	GPL13667	Tissue	118	13
GSE62452	USA	2016	GPL6244	Tissue	69	61
GSE86436	People’s Republic of China	2016	GPL13825	Tissue	6	6
GSE77858	USA	2016	GPL7264	Tissue	77	3
GSE91035	USA	2016	GPL22763	Tissue	25	23

Abbreviations: GEO, Gene Expression Omnibus; PC, pancreatic cancer.

Figure 1 Forest plot of 27 GEO datasets evaluating the SMD of MALAT1 in the PC group and the healthy control group (a fixed-effect model).

Abbreviations: CI, confidence interval; GEO, Gene Expression Omnibus; PC, pancreatic cancer; SMD, standard mean difference.

Figure 2 Sensitivity analysis to evaluate the heterogeneity among 27 GEO datasets.

Note: The results were computed by omitting each dataset in turn.
Abbreviations: CI, confidence interval; GEO, Gene Expression Omnibus.

Figure 3 Forest plot of 25 GEO datasets evaluating the SMD of MALAT1 in the PC group and the healthy control group after omitting two datasets (GSE15471 and GSE62165) (a fixed-effect model).

Abbreviations: CI, confidence interval; GEO, Gene Expression Omnibus; PC, pancreatic cancer; SMD, standard mean difference.

Figure 4 Begg’s funnel plot evaluating the publication bias among the 25 datasets.

Abbreviations: CI, confidence interval; SE, standard error; SMD, standard mean difference.

Figure 5 Summary of the ROC curve of 25 datasets evaluating the diagnostic value of MALAT1 in PC.

Abbreviations: AUC, area under the curve; CI, confidence interval; PC, pancreatic cancer; ROC, receiver operating characteristic; SENS, sensitivity; SPEC, specificity; SROC, summary receiver operating characteristic.

Figure 6 Forest plot of 25 datasets evaluating the diagnostic value of MALAT1 in PC.

Notes: (A) Pooled sensitivity and specificity of 25 datasets. (B) Pooled diagnostic OR of 25 datasets.
Abbreviations: OR, odds ratio; PC, pancreatic cancer.

Figure 7 Box plot validating the expression of MALAT1 in the PC group and the healthy control group based on the Oncomine database.

Notes: (A) The expression of MALAT1 in Grutzmann’s dataset (http://www.ebi.ac.uk/arrayexpress/experiments/E-MEXP-950). (B) The expression of MALAT1 in Badea’s datasets (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15471). (C) The expression of MALAT1 in lacobuzio-Donahue’s dataset (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3654; http://genome-www.stanford.edu/pancreatic1/index.shtml). (D) The expression of MALAT1 in Pie’s dataset (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16515). (E) The expression of MALAT1 in Ishikawa’s dataset (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1542).
Abbreviation: PC, pancreatic cancer.

Figure 8 Survival analysis evaluating the prognostic value of MALAT1 in PC.

Notes: (A) Patients with PC were divided into two groups according to MALAT1 alteration. (B) Patients with PC were divided into two groups according to MALAT1 expression.
Abbreviation: PC, pancreatic cancer.

Figure 9 Significant MF network constructed by Cytoscape 3.40.

Notes: Each node represents a GO item. Colored nodes indicate significance (P<0.01). Node size represents the involved MF items.
Abbreviations: GO, Gene Ontology; MF, molecular function.

Figure 10 Hub genes obtained from the PPI network.

Note: A degree ≥10 was chosen as the cut-off point.
Abbreviation: PPI, protein–protein interaction.

Table 2 Significant GO and KEGG items of the overlapping genes

Category	Term	Count	P-value	Benjamini	FDR
GOTERM_BP_FAT	GO:0046907~intracellular transport	26	2.06E-05	0.032809	0.034527
GOTERM_BP_FAT	GO:0051174~regulation of phosphorus metabolic process	21	4.84E-05	0.038433	0.081107
GOTERM_BP_FAT	GO:0019220~regulation of phosphate metabolic process	21	4.84E-05	0.038433	0.081107
GOTERM_BP_FAT	GO:0042325~regulation of phosphorylation	20	8.74E-05	0.046107	0.146486
GOTERM_BP_FAT	GO:0042127~regulation of cell proliferation	26	0.000361	0.136005	0.603502
GOTERM_BP_FAT	GO:0045859~regulation of protein kinase activity	15	0.000791	0.226216	1.318661
GOTERM_BP_FAT	GO:0006915~apoptosis	21	0.00083	0.200893	1.383248
GOTERM_BP_FAT	GO:0012501~programmed cell death	21	0.000996	0.205897	1.656699
GOTERM_BP_FAT	GO:0043549~regulation of kinase activity	15	0.001101	0.199873	1.829703
GOTERM_BP_FAT	GO:0006468~protein amino acid phosphorylation	22	0.001215	0.196549	2.01821
GOTERM_CC_FAT	GO:0031974~membrane-enclosed lumen	43	0.000252	0.073845	0.337322
GOTERM_CC_FAT	GO:0031981~nuclear lumen	36	0.000284	0.042315	0.380158
GOTERM_CC_FAT	GO:0000228~nuclear chromosome	10	0.000299	0.029887	0.400137
GOTERM_CC_FAT	GO:0043233~organelle lumen	41	0.000671	0.049713	0.894362
GOTERM_CC_FAT	GO:0043232~intracellular nonmembrane-bounded organelle	53	0.000793	0.047075	1.056321
GOTERM_CC_FAT	GO:0043228~nonmembrane-bounded organelle	53	0.000793	0.047075	1.056321
GOTERM_CC_FAT	GO:0005793~ER–Golgi intermediate compartment	5	0.00204	0.098288	2.697165
GOTERM_CC_FAT	GO:0000267~cell fraction	27	0.002078	0.086396	2.747502
GOTERM_CC_FAT	GO:0005624~membrane fraction	22	0.002295	0.083602	3.029516
GOTERM_CC_FAT	GO:0005875~microtubule-associated complex	7	0.002312	0.075206	3.05179
GOTERM_MF_FAT	GO:0046983~protein dimerization activity	21	0.000154	0.061492	0.215993
GOTERM_MF_FAT	GO:0001882~nucleoside binding	43	0.000155	0.031399	0.217151
GOTERM_MF_FAT	GO:0001883~purine nucleoside binding	42	0.000274	0.036878	0.383329
GOTERM_MF_FAT	GO:0000166~nucleotide binding	53	0.000428	0.043003	0.597241
GOTERM_MF_FAT	GO:0032553~ribonucleotide binding	45	0.000667	0.053362	0.929846
GOTERM_MF_FAT	GO:0032555~purine ribonucleotide binding	45	0.000667	0.053362	0.929846
GOTERM_MF_FAT	GO:0017076~purine nucleotide binding	46	0.000898	0.059685	1.25016
GOTERM_MF_FAT	GO:0019003~GDP binding	4	0.001858	0.103456	2.570935
GOTERM_MF_FAT	GO:0032559~adenyl ribonucleotide binding	37	0.002135	0.104001	2.948878
GOTERM_MF_FAT	GO:0030554~adenyl nucleotide binding	38	0.00282	0.120983	3.87696
KEGG_PATHWAY	hsa04150:mTOR signaling pathway	6	0.001995	0.195612	2.227286
KEGG_PATHWAY	hsa05200:Pathways in cancer	13	0.011181	0.458169	11.91115
KEGG_PATHWAY	hsa04010:MAPK signaling pathway	11	0.017441	0.472326	18.00035
KEGG_PATHWAY	hsa04110:Cell cycle	7	0.021605	0.44854	21.83569
KEGG_PATHWAY	hsa05218:Melanoma	5	0.035037	0.540452	33.12075
KEGG_PATHWAY	hsa05219:Bladder cancer	4	0.036427	0.490394	34.19945
KEGG_PATHWAY	hsa05212:PC	5	0.036617	0.440598	34.34575

Abbreviations: FDR, false discovery rate; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; PC, pancreatic cancer.