Comprehensive analysis of the relationship between cuproptosis-related genes and esophageal cancer prognosis

Table 1 Demographic characteristics and clinicopathological characteristics

Variables	Total, n = 151	Esophagus cancer, n = 151
		Adenocarcinoma, n = 74	Squamous cell carcinoma, n = 77
Age, yr
Median	60	68.5	57
Interquartile range	(53-72)	(57-77)	(51-63.5)
Sex
Female	22 (14.6%)	11 (14.9%)	11 (14.3%)
Male	129 (85.4%)	63 (85.1%)	66 (85.7%)
AJCC-TNM Stage
Ⅰ	18 (11.9%)	11 (14.9%)	7 (9.1%)
Ⅱ	70 (46.4%)	24 (32.4%)	46 (59.7%)
Ⅲ	51 (33.8%)	31 (41.9%)	20 (26.0%)
Ⅳ	12 (7.9%)	8 (10.8%)	4 (5.2%)
EGFR status
Mutant	5 (3.3%)	3 (4.1%)	2 (2.6%)
Wild-type	146 (96.7%)	71 (95.9%)	75 (97.4%)
KRAS status
Mutant	2 (1.3%)	2 (2.7%)	0 (0)
Wild-type	149 (98.7%)	72 (97.3%)	77 (100%)
BRAF status
Mutant	1 (0.7%)	0 (0)	1 (1.3%)
Wild-type	150 (99.3%)	74 (100%)	76 (98.7)
PIK3CA status
Mutant	14 (9.3%)	4 (5.4%)	10 (13.0%)
Wild-type	137 (90.7%)	70 (94.6%)	67 (87.0%)
OS event
Event	58 (38.4%)	36 (48.6%)	22 (28.6%)
Non-event	93 (61.6%)	38 (51.4%)	55 (71.4%)
OS months
Median	13.4	14.8	13.0
Range	(7.8-22.9)	(7.3-27.5)	(11.0-18.6)
PFS event
Event	73 (48.3%)	38 (51.4%)	35 (45.5%)
Non-event	78 (51.7%)	36 (48.6%)	42 (54.5%)
PFS months
Median	10.7	10.3	10.7
Range	(5.1-18.9)	(5.4-24.5)	(3.7-15.8)

AJCC: American Joint Committee on Cancer; BRAF: v-Raf murine sarcoma viral oncogene homolog B1 genes; EGFR: Epidermal growth factor receptor; KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; OS: Overall survival; PFS: Progression-free survival; PIK3CA: Phosphatidylino-sitol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; TNM: Tumor-node-metastasis.

Table 2 Relationship between the clinicopathological characteristics and survival outcome

Parameters	Overall survival			Progression-free survival
	Non-event	Event	P value	Non-event	Event	P value
Age, yr			0.758			0.628
≤ 65	57	37		50	44
> 65	36	21		28	29
Sex			0.102			0.009
Female	17	5		17	5
Male	76	53		61	68
AJCC-TNM stage			0.021			0.013
I and II	61	27		53	35
III and IV	32	31		25	38
Pathological type			0.011			0.469
Adenocarcinoma	38	36		36	38
SCC	55	22		42	35
EGFR status						0.596
Wild-type	3	2	0.941	2	3
Mutant	90	56		76	70
BRAF status			0.428			0.332
Wild-type	1	0		1	0
Mutant	92	58		77	73
KRAS status			0.734			0.962
Wild-type	1	1		1	1
Mutant	92	57		77	72
PIK3CA status			0.828			0.896
Wild-type	9	5		7	7
Mutant	84	53		71	66

AJCC: American Joint Committee on Cancer; BRAF: v-Raf murine sarcoma viral oncogene homolog B1 genes; EGFR: Epidermal growth factor receptor; KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; PIK3CA: Phosphatidylino-sitol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; SCC: Squamous cell carcinoma; TNM: Tumor-node-metastasis.

Table 3 The results of the univariate Cox regression analysis

Gene name	HR	HR.95L	HR.95H	P value
PDHA1	22.96	3.09	170.73	0.002
ATP7A	3.83	0.96	15.21	0.057
CDKN2A	0.84	0.64	1.10	0.204
PDHB	1.76	0.37	8.50	0.479
GLS	1.50	0.48	4.67	0.484
ATP7B	1.15	0.77	1.71	0.496
FDX1	1.52	0.41	5.59	0.527
DLD	1.82	0.27	12.11	0.534
LIPT2	0.87	0.46	1.64	0.662
DLST	0.58	0.05	6.70	0.662
NFE2L2	0.73	0.18	3.04	0.666
DLAT	1.43	0.23	8.89	0.702
DBT	0.83	0.27	2.54	0.744
GCSH	0.87	0.32	2.36	0.777
MTF1	0.85	0.26	2.80	0.785
LIAS	0.86	0.25	2.93	0.806
NLRP3	0.91	0.44	1.90	0.809
LIPT1	1.14	0.29	4.41	0.853
SLC31A1	1.08	0.19	6.15	0.928

HR: Hazard ratio; HR.95L: Low 95% confidence interval of HR; HR.95H: High 95% confidence interval of HR.

Table 4 Univariate and multivariate Cox regression analyses of pyruvate dehydrogenase A1 expression and the clinicopathological factors in the esophagus cancer patients

Variables	Overall survival		Progression-free survival
	HR (95%CI of HR)	P value	HR (95%CI of HR)	P value
PDHA1 low	1.00 (Reference)		1.00 (Reference)
UVA PDHA1 high	2.34 (1.42-3.87)	0.0009	1.51 (0.95-2.38)	0.08
MVA PDHA1 high	1.67 (1.03-2.73)	0.0386
Age ≤ 65	1.00 (Reference)		1.00 (Reference)
Age > 65	0.81 (0.47-1.41)	0.46	0.97 (0.60-1.55)	0.89
Sex, Female	1.00 (Reference)		1.00 (Reference)
UVA Male	2.12 (0.84-5.34)	0.11	2.97 (1.19-7.39)	0.02
MVA Male			2.27 (0.90- 5.73)	0.08
Pathological types, adenocarcinoma	1.00 (Reference)		1.00 (Reference)
SCC	0.81 (0.47-1.39)	0.45	1.11 (0.70-1.77)	0.66
AJCC stage I, II	1.00 (Reference)		1.00 (Reference)
UVA AJCC stage III, IV	2.53 (1.76-3.64)	5.86 × 10-7	1.98 (1.46-2.67)	9.48 × 10-6
MVA AJCC stage III, IV	2.30 (1.58-3.35)	1.46 × 10-5	1.86 (1.37-2.52)	6.98 × 10-5

CI: Confidence interval; HR: Hazard ratio; PDHA1: Pyruvate Dehydrogenase A1; UVA: Univariate; MVA: Multivariate; SCC: Squamous cell carcinoma.