Table A4.

Multivariate analysis of association between metabolites in ASNS-catalyzed asparagine synthesis metabolic pathway and OS and RFS by sex using data with complete records of KRAS mutation information (N = 161, females = 78, males = 83).

Variable a	OS						RFS
	Females			Males			Females			Males
	HR	95% CI	p Value	HR	95% CI	p Value	HR	95% CI	p Value	HR	95% CI	p Value
Asparagine	6.79	1.43–32.16	0.016	0.77	0.42–1.42	0.407	15.23	2.23–104.27	0.006	1.37	0.66–2.82	0.397
Aspartate	1.01	0.35–2.92	0.984	1.33	0.76–2.32	0.319	1.38	0.42–4.49	0.594	1.55	0.81–2.97	0.190
Glutamate	0.30	0.04–1.99	0.211	1.21	0.34–4.31	0.771	0.32	0.03–3.50	0.348	0.42	0.08–2.12	0.291
Glutamine	0.12	0.01–0.93	0.044	0.96	0.24–3.74	0.949	0.02	0.002–0.21	0.001	0.39	0.07–2.11	0.276
AMP	0.99	0.35–2.77	0.981	0.62	0.34–1.13	0.117	1.07	0.33–3.45	0.915	0.76	0.32–1.88	0.554
KRAS = mutant (ref: wild type)	1.34	0.32–5.67	0.69	0.54	0.17–1.68	0.286	1.69	0.36–7.94	0.505	0.77	0.16–3.76	0.748
Anatomic location = RCC (ref: LCC)	1.50	0.43–5.31	0.527	0.83	0.26–2.71	0.759	0.82	0.21–3.25	0.777	0.76	0.17–3.47	0.721
Clinical stage = late (ref: early)	9.66	1.34–69.57	0.024	8.09	1.42–46.22	0.019	1.31	0.19–9.03	0.782	0.61	0.07–4.78	0.636
Chemotherapy = Yes (ref: no)	1.80	0.37–8.74	0.468	0.46	0.07–2.85	0.402	3.55	0.47–26.49	0.217	3.33	0.37–29.78	0.283
Age	1.09	0.97–1.23	0.154	1.14	1.05–1.231	0.001	1.05	0.94–1.17	0.407	0.95	0.87–1.05	0.331

^a All of the variables listed were included in one multivariate Cox PH model. The abundance of each metabolite was treated as a continuous variable and was log₂ transformed.