Significant Prognostic Factor at Age Cut-off of 73 Years for Advanced Ovarian Serous Cystadenocarcinoma Patients: Insights from Real-World Study

Figures & data

Figure 1 Flowchart for screening patients.

Figure 2 X-Tile analysis of survival data from the SEER database. (A) The X-Tile plot displays red coloration of cut-points, indicating a negative correlation with survival, while green coloration represents a positive correlation. The plot illustrates patient age divided at the mean age, and the optimal cut-point is highlighted by a black circle located in the middle of the color bar. (B) The histogram of the entire cohort reveals that the optimal cut-off value of age at diagnosis is 73 years, based on cancer-specific survival (CSS). The X-axis represents the age of patients, and the Y-axis represents the number of patients at each age. (C) The Kaplan-Meier survival curve is generated based on these cut-off values.

Table 1 Baseline Characteristics of Patients with Advanced Ovarian Serous Cystadenocarcinoma in the SEER Database, n(%)

Characteristics	Before PSM				After PSM
	Total	Young (≤73y)	Old (> 73y)	P value	Total	Young (≤73y)	Old (> 73y)	P value
All	20,846	16,336(78.4%)	4510(21.6%)		8504	4252(50.0%)	4252(50.0%)
Race				<0.001				0.812
White	17,733(85.1%)	13,711(83.9%)	4022(89.2%)		7524(88.5%)	3754(88.3%)	3770(88.7%)
Black	1572(7.5%)	1314(8.0%)	258(5.7%)		517(6.1%)	260(6.1%)	257(6.0%)
Other	1541(7.4%)	1311(8.0%)	230(5.1%)		463(5.4%)	238(5.6%)	225(5.3%)
Marital				<0.001				0.940
Single	3096(14.9%)	2769(17.0%)	327(7.3%)		652(7.7%)	325(7.6%)	327(7.7%)
Married	11,222(53.8%)	9460(57.9%)	1762(39.1%)		3540(41.6%)	1778(41.8%)	1762(41.4%)
Other	6528(31.3%)	4107(25.1%)	2421(53.7%)		4312(50.7%)	2149(50.5%)	2163(50.9%)
FIGO				<0.001				0.259
III	13449(64.5%)	10,677(65.4%)	2772(61.5%)		5443(64.0%)	2696(63.4%)	2747(64.6%)
IV	7397(35.5%)	5659(34.6%)	1738(38.5%)		3061(36.0%)	1556(36.6%)	1505(35.4%)
Grade				<0.001				0.283
I	426(2.0%)	371(2.3%)	55(1.2%)		90(1.1%)	36(0.8%)	54(1.3%)
II	1802(8.6%)	1506(9.2%)	296(6.6%)		608(7.1%)	313(7.4%)	295(6.9%)
III	8596(41.2%)	6929(42.4%)	1667(37.0%)		3311(38.9%)	1673(39.3%)	1638(38.5%)
IV	5522(26.5%)	4485(27.5%)	1037(23.0%)		2013(23.7%)	990(23.3%)	1023(24.1%)
Unknown	4500(21.6%)	3045(18.6%)	1455(32.3%)		2482(29.2%)	1240(29.2%)	1242(29.2%)
Laterality				<0.001				0.932
Unilateral	7029(33.7%)	5226(32.0%)	1803(40.0%)		3488(41.0%)	1752(41.2%)	1736(40.8%)
Bilateral	11,851(56.9%)	9971(61.0%)	1880(41.7%)		3752(44.1%)	1872(44.0%)	1880(44.2%)
Unknown	1966(9.4%)	1139(7.0%)	827(18.3%)		1264(14.9%)	628(14.8%)	636(15.0%)
Surgery				<0.001				0.824
FSS	1297(6.2%)	907(5.6%)	390(8.6%)		731(8.6%)	368(8.7%)	363(8.5%)
RS	5653(27.1%)	4740(29.0%)	913(20.2%)		1847(21.7%)	934(22.0%)	913(21.5%)
Other	13,896(66.7%)	10,689(65.4%)	3207(71.1%)		5926(69.7%)	2950(69.4%)	2976(70.0%)
Chemotherapy				<0.001				0.641
Yes	17,786(85.3%)	14,437(88.4%)	3349(74.3%)		6581(77.4%)	3300(77.6%)	3281(77.2%)
No/Unknown	3060(14.7%)	1899(11.6%)	1161(25.7%)		1923(22.6%)	952(22.4%)	971(22.8%)
Radiation				0.058				0.058
Yes	217(1.0%)	182(1.1%)	35(0.8%)		55(0.6%)	20(0.5%)	35(0.8%)
No/Unknown	20,629(99.0%)	16,154(98.9%)	4475(99.2%)		8449(99.4%)	4232(99.5%)	4217(99.2%)
CA125				<0.001				0.381
Positive	16,504(79.2%)	13,065(80.0%)	3439(76.3%)		6566(77.2%)	3279(77.1%)	3287(77.3%)
Negative	624(3.0%)	474(2.9%)	150(3.3%)		276(3.2%)	128(3.0%)	148(3.5%)
Other	3718(17.8%)	2797(17.1%)	921(20.4%)		1662(19.5%)	845(19.9%)	817(19.2%)

Abbreviations: FSS, fertility-sparing surgery; RS, radical surgery.

Table 2 The Cox Hazard Regression Analysis of Overall Survival

Characteristic	Univariate Analysis Before PSM		Multivariate Analysis Before PSM		Univariate Analysis After PSM		Multivariate Analysis After PSM
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age
Young (≤73y)	Reference		Reference		Reference		Reference
Old (>73y)	1.979(1.908–2.052)	<0.001	1.767(1.701–1.837)	<0.001	1.624(1.548–1.703)	<0.001	1.701(1.621–1.785)	<0.001
Race
White	Reference		Reference		Reference		Reference
Black	1.180(1.113–1.252)	<0.001	1.179(1.111–1.251)	<0.001	1.267(1.150–1.396)	<0.001	1.152(1.045–1.270)	0.004
Other	0.890(0.836–0.947)	<0.001	0.920(0.864–0.979)	0.009	0.944(0.849–1.049)	0.281	0.927(0.833–1.030)	0.901
Marital
Single	Reference		Reference		Reference		Reference
Married	0.963(0.918–1.009)	0.112	0.948(0.904–0.994)	0.028	0.777(0.708–0.852)	<0.001	0.786(0.717–0.863)	<0.001
Other	1.374(1.307–1.444)	<0.001	1.166(1.108–1.227)	<0.001	0.978(0.893–1.071)	0.635	0.994(0.908–1.089)	0.353
FIGO
III	Reference		Reference		Reference		Reference
IV	1.566(1.516–1.618)	<0.001	1.452(1.405–1.500)	<0.001	1.491(1.420–1.566)	<0.001	1.400(1.332–1.470)	<0.001
Grade
I	Reference		Reference		Reference		Reference
II	1.793(1.558–2.064)	<0.001	1.739(1.511–2.002)	<0.001	1.546(1.187–2.014)	<0.001	1.757(1.348–2.291)	<0.001
III	2.016(1.766–2.301)	<0.001	1.855(1.624–2.118)	<0.001	1.599(1.243–2.057)	<0.001	1.793(1.392–2.310)	<0.001
IV	1.894(1.657–2.165)	<0.001	1.770(1.548–2.025)	<0.001	1.509(1.171–1.946)	<0.001	1.705(1.320–2.202)	<0.001
Unknown	2.674(2.338–3.057)	<0.001	2.010(1.756–2.301)	<0.001	2.070(1.608–2.665)	<0.001	2.034(1.576–2.625)	<0.001
Laterality
Unilateral	Reference		Reference		Reference		Reference
Bilateral	1.013(0.978–1.049)	0.469	1.083(1.046–1.122)	<0.001	1.118(1.062–1.178)	<0.001	1.111(1.055–1.171)	<0.001
Unknown	1.951(1.846–2.062)	<0.001	1.547(1.459–1.641)	<0.001	1.713(1.596–1.837)	<0.001	1.486(1.379–1.602)	<0.001
Surgery
FSS	Reference		Reference		Reference		Reference
RS	0.868(0.809–0.932)	<0.001	0.968(0.901–1.039)	0.367	0.934(0.847–1.029)	0.165	0.930(0.843–1.025)	0.142
Other	1.176(1.100–1.256)	<0.001	1.227(1.147–1.312)	<0.001	1.272(1.166–1.388)	<0.001	1.236(1.133–1.350)	<0.001
Chemotherapy
Yes	Reference		Reference		Reference		Reference
No/Unknown	1.528(1.464–1.595)	<0.001	1.499(1.435–1.566)	<0.001	1.463(1.384–1.547)	<0.001	1.603(1.514–1.696)	<0.001
Radiation
Yes	Reference		Reference		Reference
No/Unknown	0.820(0.709–0.948)	0.007	0.754(0.652–0.871)	<0.001	0.841(0.632–1.121)	0.238
CA125
Positive	Reference		Reference		Reference		Reference
Negative	0.621(0.559–0.689)	<0.001	0.646(0.582–0.717)	<0.001	0.686(0.594–0.793)	<0.001	0.707(0.611–0.816)	<0.001
Other	1.009(0.969–1.052)	0.659	0.925(0.887–0.965)	<0.001	0.988(0.931–1.049)	0.697	0.935(0.880–0.994)	0.030

Abbreviations: FSS, fertility-sparing surgery; RS, radical surgery.

Table 3 The Cox Hazard Regression Analysis of Cancer-Specific Survival

Characteristic	Univariate Analysis Before PSM		Multivariate Analysis Before PSM		Univariate Analysis After PSM		Multivariate Analysis After PSM
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Age
Young(≤73y)	Reference		Reference		Reference		Reference
Old(>73y)	1.870(1.799–1.943)	<0.001	1.681(1.614–1.751)	<0.001	1.538(1.462–1.617)	<0.001	1.608(1.528–1.691)	<0.001
Race
White	Reference		Reference		Reference		Reference
Black	1.174(1.104–1.249)	<0.001	1.174(1.103–1.249)	<0.001	1.272(1.149–1.409)	<0.001	1.161(1.047–1.286)	0.005
Other	0.882(0.826–0.941)	<0.001	0.908(0.850–0.969)	0.004	0.915(0.817–1.025)	0.125	0.900(0.803–1.008)	0.068
Marital
Single	Reference		Reference		Reference		Reference
Married	0.975(0.928–1.024)	0.304	0.962(0.915–1.011)	0.122	0.804(0.729–0.888)	0.004	0.815(0.738–0.900)	<0.001
Other	1.351(1.282–1.424)	<0.001	1.163(1.103–1.227)	<0.001	0.987(0.896–1.087)	0.786	1.006(0.913–1.109)	0.899
FIGO
III	Reference		Reference		Reference		Reference
IV	1.582(1.530–1.637)	<0.001	1.468(1.418–1.519)	<0.001	1.517(1.441–1.597)	<0.001	1.419(1.347–1.495)	<0.001
Grade
I	Reference		Reference		Reference		Reference
II	1.986(1.703–2.316)	<0.001	1.916(1.642–2.234)	<0.001	2.046(1.491–2.808)	<0.001	2.274(1.655–3.124)	<0.001
III	2.219(1.919–2.566)	<0.001	2.035(1.759–2.354)	<0.001	2.086(1.537–2.830)	<0.001	2.297(1.691–3.121)	<0.001
IV	2.093(1.807–2.424)	<0.001	1.942(1.676–2.251)	<0.001	1.994(1.466–2.710)	<0.001	2.200(1.615–2.996)	<0.001
Unknown	2.905(2.508–3.366)	<0.001	2.186(1.885–2.536)	<0.001	2.716(2.000–3.688)	<0.001	2.603(1.912–3.542)	<0.001
Laterality
Unilateral	Reference		Reference		Reference		Reference
Bilateral	1.043(1.005–1.081)	0.025	1.105(1.065–1.146)	<0.001	1.160(1.098–1.226)	<0.001	1.150(1.088–1.215)	<0.001
Unknown	1.961(1.850–2.079)	<0.001	1.566(1.472–1.666)	<0.001	1.754(1.629–1.890)	<0.001	1.510(1.395–1.634)	<0.001
Surgery
FSS	Reference		Reference		Reference		Reference
RS	0.878(0.814–0.946)	0.001	0.967(0.897–1.043)	0.383	0.934(0.841–1.036)	0.196	0.928(0.836–1.031)	0.163
Other	1.206(1.124–1.293)	<0.001	1.243(1.158–1.334)	<0.001	1.323(1.206–1.453)	<0.001	1.275(1.161–1.401)	<0.001
Chemotherapy
Yes	Reference		Reference		Reference		Reference
No/Unknown	1.471(1.405–1.539)	<0.001	1.457(1.391–1.527)	<0.001	1.419(1.338–1.506)	<0.001	1.559(1.468–1.657)	<0.001
Radiation
Yes	Reference		Reference		Reference
No/Unknown	0.819(0.704–0.953)	0.010	0.755(0.649–0.879)	<0.001	0.838(0.619–1.136)	0.255
CA125
Positive	Reference		Reference		Reference		Reference
Negative	0.613(0.550–0.684)	<0.001	0.644(0.577–0.719)	<0.001	0.673(0.577–0.784)	<0.001	0.702(0.602–0.818)	<0.001
Other	0.992(0.950–1.036)	0.728	0.918(0.878–0.959)	<0.001	0.964(0.905–1.027)	0.257	0.921(0.863–0.982)	0.012

Abbreviations: FSS, fertility-sparing surgery; RS, radical surgery.

Figure 3 Kaplan-Meier curves of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier curves of OS (A) and CSS (B) before propensity score matching (PSM), Kaplan-Meier curves of OS (C) and CSS (D) after PSM.

Figure 4 The forest plot of subgroup analyses according to age (young vs old) of patients with advanced serous ovarian cystadenocarcinoma in the PSM cohort from the SEER database.

Figure 5 Differentially expressed genes (DEGs) between the old group and the young group. (A) The heatmap of DEGs. (B) The volcano plot of DEGs. (C) A bar chart of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs. (D) A bar chart of Gene Ontology (GO) analysis of DEGs. (E) The protein-protein interaction network of DEGs.

Figure 6 Survival analysis of DEGs. Kaplan-Meier analysis is developed based on the expression levels of AKT1 (A), SUPT3H (B), RELA (C), TAB3 (D), and TBP (E).

Data Sharing Statement

The following information was supplied regarding data availability: Data is available at the SEER database (https://seer.cancer.gov/) and the TCGA database (https://portal.gdc.cancer.gov/).