Construction and validation of chemotherapy resistance prediction model for ovarian cancer

doi:10.11958/20240546

Abstract

Abstract:

Objective To investigate the influencing factors on the occurrence of chemo-resistance after postoperative chemotherapy in ovarian cancer patients, and construct a prediction model and evaluate the model efficacy. Methods The clinical data of 407 ovarian cancer patients who underwent tumor cytoreduction and chemotherapy were collected. At the endpoint of follow-up, patients were divided into the recurrence group (n=363) and the non-recurrence group (n=44). Patients in the recurrence group were re-divided into the resistant group (n=59) and the sensitive group (n=304) according to the chemotherapy resistance. Variables were screened using univariate analysis and Lasso regression. Logistic model was established. R software was used to build a nomogram and evaluate it. Results Compared with the non-recurrence group, the age of the recurrence group was lower, and the proportion of low differentiation and the proportion of FIGO stage Ⅲ-Ⅳwere higher (P<0.05). Compared with the sensitive group, in the resistant group, lymph node enlargement, non-serous pathological type, the proportion of FIGO stage Ⅲ-Ⅳ, positive rate of immunohistochemical recombinant proteins Ki-67, protein 53 (P53), vascular endothelial growth factor (VEGF) and nephroblastoma gene 1 (WT-1) were higher. The change rate of glycan antigen 125 (CA125) before and after surgery, the change rates of Rome index (ROMA) (premenopausal) before and after chemotherapy and the positive rate of immunohistochemical protein 16 (P16) were lower (P<0.05). The eight variables screened by Lasso regression were used as independent variables for Logistic regression. Results showed that there were enlarged lymph nodes in preoperativeCT imaging, the pathological type was non-serous, the FIGO stages were Ⅲ-Ⅳ, and immunohistochemistry results of WT1 and VEGF were positive. P16 negative was an independent risk factor for chemo-resistance in ovarian cancer patients. Accordingly, the area under the receiver operating characteristic curve of the nomogram model established was 0.837 (0.783-0.880), and the result of Hosmer-Lemeshow test indicated a good model fit. The calibration curve and the clinical decision curve (DCA) suggested a high calibration and clinical use of the model. Conclusion We have successfully constructed a Logistic model of chemotherapy resistance in ovarian cancer based on clinical data, and the nomogram prediction model can effectively assess the risk of chemo-resistance in ovarian cancer.

Key words: ovarian neoplasms, chemoradiotherapy, drug resistance, neoplasm, Logistic models, nomograms

CLC Number:

R737.31

Figures/Tables 10

References 24

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组别		n	年龄/岁	BMI/（kg/m²）		病理类型（A/B/C/D）^＃
未复发组		44	57.7±8.1	24.4±3.6		33/4/3/4
复发组		363	52.8±9.6	23.6±3.3		283/21/32/27
t或χ²			3.262^＊＊	1.482		1.065
组别	组织学分级（高/中/低分化）				FIGO分期（Ⅰ/Ⅱ/Ⅲ/Ⅳ）
未复发组	23/6/15				11/14/18/1
复发组	45/89/229				72/41/223/27
Z	2.192^＊				2.924^＊＊

组别		n	年龄/岁	BMI/（kg/m²）		病理类型（A/B/C/D）^＃
未复发组		44	57.7±8.1	24.4±3.6		33/4/3/4
复发组		363	52.8±9.6	23.6±3.3		283/21/32/27
t或χ²			3.262^＊＊	1.482		1.065
组别	组织学分级（高/中/低分化）				FIGO分期（Ⅰ/Ⅱ/Ⅲ/Ⅳ）
未复发组	23/6/15				11/14/18/1
复发组	45/89/229				72/41/223/27
Z	2.192^＊				2.924^＊＊

组别	n		年龄/岁		BMI/（kg/m²）		术前全腹增强CT								手术相关
组别	n		年龄/岁		BMI/（kg/m²）		肿瘤最长径/cm		腹腔积液		淋巴结增大		大网膜转移		手术时长/min		术中出血量/mL
敏感组	304		52.3±10.1		23.6±3.2		9.2±5.6		181（59.5）		100（32.9）		178（58.6）		270（210，354）		500（300，800）
耐药组	59		53.1±9.4		23.6±3.5		7.8±4.4		29（49.2）		31（52.5）		30（50.8）		290（205，350）		580（350，800）
t、χ²或Z			0.516		0.020		1.530		2.186		8.270^＊＊		1.199		0.456		0.265
组别		Hb降低值/（g/L）		手术前后血肿瘤标志物变化率/%
组别		Hb降低值/（g/L）		AFP		CA125		CA199		CEA		HE4		ROMA（绝经后）		ROMA（绝经前）
敏感组		16.0±8.9		2.3±1.0		73.5±20.6		19.2（7.5，26.2）		32.3±14.9		43.5±8.4		35.2（20.6，44.8）		53.8±15.0
耐药组		13.6±5.4		1.8±0.8		50.3±20.1		28.1（11.2，37.1）		37.8±14.4		52.7±2.8		23.4（11.2，29.5）		39.5±13.3
Z或t		0.881		1.252		7.896^＊＊		0.417		0.670		0.456		0.499		1.470

组别	n		年龄/岁		BMI/（kg/m²）		术前全腹增强CT								手术相关
组别	n		年龄/岁		BMI/（kg/m²）		肿瘤最长径/cm		腹腔积液		淋巴结增大		大网膜转移		手术时长/min		术中出血量/mL
敏感组	304		52.3±10.1		23.6±3.2		9.2±5.6		181（59.5）		100（32.9）		178（58.6）		270（210，354）		500（300，800）
耐药组	59		53.1±9.4		23.6±3.5		7.8±4.4		29（49.2）		31（52.5）		30（50.8）		290（205，350）		580（350，800）
t、χ²或Z			0.516		0.020		1.530		2.186		8.270^＊＊		1.199		0.456		0.265
组别		Hb降低值/（g/L）		手术前后血肿瘤标志物变化率/%
组别		Hb降低值/（g/L）		AFP		CA125		CA199		CEA		HE4		ROMA（绝经后）		ROMA（绝经前）
敏感组		16.0±8.9		2.3±1.0		73.5±20.6		19.2（7.5，26.2）		32.3±14.9		43.5±8.4		35.2（20.6，44.8）		53.8±15.0
耐药组		13.6±5.4		1.8±0.8		50.3±20.1		28.1（11.2，37.1）		37.8±14.4		52.7±2.8		23.4（11.2，29.5）		39.5±13.3
Z或t		0.881		1.252		7.896^＊＊		0.417		0.670		0.456		0.499		1.470

组别		n	病理类型（A/B/C/D）		组织学分级（高/中/低分化）				FIGO分期（Ⅰ/Ⅱ/Ⅲ/Ⅳ）			免疫组化阳性CDX2
敏感组		304	253/11/19/21		32/83/189				67/36/181/20			160
耐药组		59	30/10/13/6		13/6/40				5/5/42/7			35
χ²或Z			36.492^＊＊		0.097				2.817^＊＊			0.890
组别	免疫组化阳性
组别	CK	CK7	CK20	ER	Ki-67	P16	WT-1	PAX-8	PR	VEGF	Villin	P53
敏感组	171（56.2）	101（33.2）	171（56.2）	84（27.6）	207（68.1）	131（43.1）	179（58.9）	135（44.4）	56（18.4）	181（59.5）	89（29.3）	173（56.9）
耐药组	23（39.0）	16（27.1）	23（39.0）	17（28.8）	50（84.7）	16（27.1）	46（78.0）	22（37.3）	12（20.3）	45（76.3）	22（37.3）	42（71.2）
χ²	0.458	0.843	0.458	0.034	6.628^＊	5.232^＊	7.637^＊＊	1.020	0.119	5.887^＊	1.494	4.172^＊