Prediction of Key Candidate Genes for Platinum Resistance in Ovarian Cancer

Figures & data

Table 1 Primer List for Q-PCR

Primer Name	Primer Sequences (5ʹ-3ʹ)
IFI27 Forward Primer	TGCTCTCACCTCATCAGCAGT
IFI27 Reverse Primer	CACAACTCCTCCAATCACAACT
JAG1 Forward Primer	GTCCATGCAGAACGTGAACG
JAG1 Reverse Primer	GCGGGACTGATACTCCTTGA
DNM3 Forward Primer	TCGAGGGTCGGGCATTGTA
DNM3 Reverse Primer	CTTCAATCTCAAGGCGAACTTCA
GAPDH Forward Primer	GGATCTCGCTCCTGGAAGATG
GAPDH Reverse Primer	GGGAACACAAAAGACCTCTTCT

Figure 1 Venn diagram.

Figure 2 Statistical Analysis of 3 genes in ovarian cancer sensitive and drug-resistant cells from 5 gene chips. (A) The expression level of IFI27 in 5 gene chips; (B) The expression level of JAG1; (C) The expression level of DNM3.

Notes: *P < 0.05, **P < 0.01, ***P < 0.005.

Figure 3 IC₅₀ values of sensitive and cisplatin-resistant cells of ovarian cancer. (A) IC₅₀ in A2780 and A2780-DDP; (B) IC₅₀ in SKOV3 and SKOV3-DDP.

Notes: **P < 0.01, ***P < 0.005.

Figure 4 The mRNA expression of each gene in ovarian cancer sensitive and cisplatin-resistant cells by qRT-PCR. (A) mRNA expression of IFI27 in ovarian cancer cells; (B) mRNA expression of JAG1; (C) mRNA expression of DNM3.

Notes: *P < 0.05, **P < 0.01.

Figure 5 The expression of 3 genes in ovarian cancer chemosensitive and drug-resistant patients from TCGA. (A) mRNA expression of IFI27 in ovarian cancer cells; (B) mRNA expression of JAG1; (C) mRNA expression of DNM3.

Table 2 IFI27, JAG1 and DNM3 Expression and Clinicopathological Parameters of Ovarian Cancer in TCGA

Parameters	n (%)	IFI27 Expression		χ^2	P value	JAG1 Expression		χ^2	P value	DNM3 Expression		χ^2	P value
		Low	High			Low	High			Low	High
Age (years)
≤55	105 (41.33)	60	45	0.715	0.398	64	41	0.092	0.762	73	32	0.267	0.605
>55	149 (58.66)	93	56			88	61			99	50
Degree of resistance
Sensitivity	205 (80.70)	130	75	8.352	0.004	87	118	5.617	0.018	137	68	4.278	0.039
Resistance	49 (19.29)	20	29			30	19			25	24
Recurrence
No	76 (29.92)	49	27	0.813	0.361	34	42	6.314	0.012	45	31	5.632	0.018
Yes	178 (70.08)	104	74			110	68			132	46
Histological grade
G1/G2	33 (12.99)	16	17	2.074	0.150	19	14	0.087	0.768	23	10	0.144	0.704
G3/G4	214 (84.25)	132	82			129	85			142	72
Missing	7 (2.76)
FIGO stage
I/II	17 (6.69)	12	5	0.745	0.388	11	6	0.203	0.652	7	10	8.175	0.004
III/IV	235 (92.52)	141	94			139	96			173	62
Missing	2 (0.79)
Tumor residue
No	55 (21.65)	18	37	11.401	0.001	32	23	0.073	0.787	35	20	0.242	0.623
Yes	186 (73.23)	109	77			112	74			125	61
Missing	13 (5.19)
Survival status
Alive	99 (38.98)	66	33	4.706	0.030	55	44	1.241	0.265	64	35	0.699	0.403
Dead	155 (61.02)	82	73			97	58			108	47

Figure 6 The relationship between the gene expression and the OS or PFS in platinum-resistant patients with ovarian cancer. (A) The relationship between IFI27 expression and the OS of ovarian cancer platinum-resistant patients; (B) IFI27 and the PFS in platinum-resistance; (C) JAG1 and the OS; (D) JAG1 and the PFS; (E) DNM3 and the OS; (F) DNM3 and the PFS.

Table 3 Binary Logistics Regression to Evaluate the Factors Influencing Platinum-Resistant Ovarian Cancer Patients

Parameters	P value	HR	95% CI
IFI27 expression level	0.017	0.434	0.219–0.861
JAG1 expression level	0.115	0.582	0.297–1.140
DNM3 expression level	0.010	3.124	1.311–7.445
Age	0.923	0.966	0.483–1.932
Survival status	0.650	1.220	0.517–2.877
Histological grade	0.887	1.071	0.418–2.746
FIGO stage	0.491	0.474	0.057–3.971
Tumor residue	0.0001	0.059	0.016–0.212
Recurrence	0.0001	5.991	2.410–14.890

Table 4 The Ability of Genes to Predict Chemotherapy Outcomes in Ovarian Cancer

Gene	AUC (95% CI)	P	Youden	Sensitivity	Specificity	Positive Likelihood Ratio	Negative Likelihood Ratio
IFI27	0.5964 (0.506–0.686)	0.0361	0.180	0.371	0.449	1.402	0.673
JAG1	0.6011 (0.510–0.692)	0.0279	0.173	0.714	0.459	1.319	0.623
DNM3	0.5812 (0.497–0.666)	0.0775	0.175	0.298	0.878	2.430	0.800

Abbreviation: AUC, area under the curve.

Figure 7 ROC curves to determine the genes as indicators of ovarian cancer chemosensitivity (A–C).