FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma

Table 1 Patient Characteristics of individuals with stomach adenocarcinoma in The Cancer Genome Atlas datasets, n (%)

Characteristic	Levels	Overall (n = 375)
T stage	T1	19 (5.2)
	T2	80 (21.8)
	T3	168 (45.8)
	T4	100 (27.2)
N stage	N0	111 (31.1)
	N1	97 (27.2)
	N2	75 (21)
	N3	74 (20.7)
M stage	M0	330 (93)
	M1	25 (7)
Pathologic stage	Stage I	53 (15.1)
	Stage II	111 (31.5)
	Stage III	150 (42.6)
	Stage IV	38 (10.8)
Gender	Female	134 (35.7)
	Male	241 (64.3)
Age	≤ 65	164 (44.2)
	> 65	207 (55.8)
OS event	Alive	228 (60.8)
	Dead	147 (39.2)
DSS event	Alive	263 (74.3)
	Dead	91 (25.7)
PFI event	Alive	251 (66.9)
	Dead	124 (33.1)
Age, median (IQR)		67 (58, 73)

OS: Overall survival; DSS: Disease-specific survival; PFI: Progression-free interval.

Table 2 Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis results

Ontology	ID	Description	P value	P adjust	Q value
BP	GO: 0022900	Electron transport chain	1.62e-04	0.072	0.060
BP	GO: 0042775	Mitochondrial ATP synthesis coupled electron transport	4.05e-04	0.072	0.060
BP	GO: 0042773	ATP synthesis coupled electron transport	4.18e-04	0.072	0.060
BP	GO: 2000773	Negative regulation of cellular senescence	4.92e-04	0.072	0.060
BP	GO: 0022904	Respiratory electron transport chain	7.01e-04	0.078	0.065
CC	GO: 0005743	Mitochondrial inner membrane	5.02e-07	3.72e-05	3.07e-05
CC	GO: 0070469	Respiratory chain	5.13e-04	0.018	0.015
CC	GO: 0098798	Mitochondrial protein complex	7.23e-04	0.018	0.015
MF	GO: 0009055	Electron transfer activity	8.42e-04	0.063	0.047
KEGG	hsa00190	Oxidative phosphorylation	0.001	0.026	0.016
KEGG	hsa04932	Non-alcoholic fatty liver disease	0.002	0.026	0.016
KEGG	hsa05014	Amyotrophic lateral sclerosis	0.003	0.026	0.016
KEGG	hsa04714	Thermogenesis	0.007	0.046	0.028
KEGG	hsa05012	Parkinson disease	0.008	0.046	0.028

GO: Gene Ontology; BP: Biological process; MF: Molecular function; CC: Cellular component; KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 3 Gene Set Enrichment Analysis enrichment analysis results

ID	Enrichment score	NES	P value	Q values
HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION	0.708105259	2.990707978	0.001305483	0.008457298
HALLMARK_HYPOXIA	0.403129656	1.699699999	0.00130719	0.008457298
HALLMARK_APICAL_JUNCTION	0.461587301	1.935939035	0.001310616	0.008457298
HALLMARK_MYOGENESIS	0.66612	2.752470842	0.001331558	0.008457298
HALLMARK_COAGULATION	0.50179623	1.942687567	0.00143472	0.008457298
HALLMARK_UV_RESPONSE_DN	0.406876695	1.662984536	0.002702703	0.009857419
hallmark_interferon_alpha_response	-0.423867587	-1.8197451	0.003257329	0.009857419
HALLMARK_G2M_CHECKPOINT	-0.566300626	-2.681102853	0.004255319	0.009857419
hallmark_interferon_gamma_response	-0.329292011	-1.559005425	0.004255319	0.009857419
HALLMARK_E2F_TARGETS	-0.562672699	-2.6759039	0.004329004	0.009857419
HALLMARK_MYC_TARGETS_V1	-0.454693047	-2.162384814	0.004329004	0.009857419
HALLMARK_MITOTIC_SPINDLE	-0.367141984	-1.748758241	0.004347826	0.009857419
HALLMARK_MTORC1_SIGNALING	-0.385874626	-1.837984926	0.004347826	0.009857419
HALLMARK_MYC_TARGETS_V2	-0.448665513	-1.728129282	0.005617978	0.011827321
HALLMARK_INFLAMMATORY_RESPONSE	-0.318801368	-1.472576393	0.00862069	0.016938899
HALLMARK_PROTEIN_SECRETION	-0.367157298	-1.567228573	0.009771987	0.018001029
HALLMARK_ANGIOGENESIS	0.547725076	1.690092924	0.014802632	0.025664005
HALLMARK_IL6_JAK_STAT3_SIGNALING	-0.367388389	-1.508170458	0.018181818	0.029771398
HALLMARK_KRAS_SIGNALING_DN	0.371059103	1.431772189	0.024425287	0.037786775
hallmark_estrogen_response_late	-0.291604703	-1.348128819	0.025641026	0.037786775
HALLMARK_UNFOLDED_PROTEIN_RESPONSE	-0.323403998	-1.423443484	0.029315961	0.041145208
HALLMARK_HEDGEHOG_SIGNALING	0.472117157	1.469309232	0.045602606	0.0610944

Table 4 Univariate/multivariate Cox regression

Characteristics	Total (n)	Univariate analysis		Multivariate analysis
		Hazard ratio (95%CI)	P value	Hazard ratio (95%CI)	P value
FDX1	370
High	184	Reference
Low	186	1.282 (0.922-1.784)	0.140
LIAS	370
High	183	Reference
Low	187	1.501 (1.075-2.095)	0.017	1.414 (0.981-2.038)	0.063
MTF1	370
High	185	Reference
Low	185	1.368 (0.985-1.900)	0.061	1.346 (0.936-1.936)	0.109
T stage	362
T1	18	Reference
T2	78	6.725 (0.913-49.524)	0.061	4.323 (0.548-34.111)	0.165
T3	167	9.548 (1.326-68.748)	0.025	5.338 (0.613-46.515)	0.129
T4	99	9.634 (1.323-70.151)	0.025	5.141 (0.576-45.881)	0.143
N stage	352
N0	107	Reference
N1	97	1.629 (1.001-2.649)	0.049	1.152 (0.578-2.296)	0.688
N2	74	1.655 (0.979-2.797)	0.060	1.298 (0.553-3.050)	0.549
N3	74	2.709 (1.669-4.396)	< 0.001	1.818 (0.772-4.281)	0.171
M stage	352
M0	327	Reference
M1	25	2.254 (1.295-3.924)	0.004	1.038 (0.430-2.504)	0.935
Pathologic stage	347
Stage I	50	Reference
Stage II	110	1.551 (0.782-3.078)	0.209	1.132 (0.399-3.212)	0.816
Stage III	149	2.381 (1.256-4.515)	0.008	1.181 (0.304-4.588)	0.810
Stage IV	38	3.991 (1.944-8.192)	< 0.001	2.082 (0.513-8.445)	0.305