Roles of Notch1 mRNA and Dickkopf-1 in assessing the therapeutic responsiveness of pembrolizumab in non-small cell lung cancer patients

doi:10.3969/j.issn.1673-8640.2024.07.002

Abstract

Abstract:

Objective To investigate the roles of Notch1 mRNA and Dickkopf-1 in assessing the therapeutic responsiveness of pembrolizumab in non-small cell lung cancer （NSCLC）patients. Methods Totally，169 patients with NSCLC treated in Handan Central Hospital from July 2020 to September 2022 were enrolled as observation group，and 168 patients with benign lung nodules were enrolled as control group. The clinical data of all the patients were collected，and the relative expression of serum Notch1 mRNA and Dickkopf-1 level in control group before treatment and at 3 and 6 weeks after pembrolizumab treatment were determined. The therapeutic responsiveness [disease progression （PD），disease control （DC）] at 6 weeks after pembrolizumab treatment in NSCLC patients was evaluated. Receiver operating characteristic （ROC） curve was used to evaluate the efficacy of Notch1 mRNA and Dickkopf-1 in judging the therapeutic responsiveness of pembrolizumab before treatment. Logistic regression model was used to analyze the influencing factors of therapeutic responsiveness of pembrolizumab. Results Serum Notch1 mRNA relative expression and Dickkopf-1 level in NSCLC group were higher than those in control group before treatment and at 3 and 6 weeks after treatment（P<0.001）. The relative expression of serum Notch1 mRNA and Dickkopf-1 level in NSCLC group were decreased successively before treatment and at 3 and 6 weeks after treatment （P<0.001）. There was statistical significance in age，the Eastern Cooperative Oncology Group（ECOG） score，clinical stage，lymphatic metastasis，distant metastasis，differentiation degree，programmed cell death-ligand 1（PD-L1）expression and serum Notch1 mRNA relative expression and Dickkopf-1 level before treatment and at 3 and 6 weeks after treatment between PD group and DC group（P<0.05）. The areas under curves （AUC） of serum Notch1 mRNA and Dickkopf-1 in assessing the therapeutic responsiveness of pembrolizumab were 0.791，0.796 and 0.861，respectively. After adjusting for confounding factors，the risk probabilities of PD in high Notch1 mRNA group and high Dickkopf-1 group before treatment were 3.517 times and 3.326 times higher than those in low Notch1 mRNA group and low Dickkopf-1 group [odds ratios （OR） were 3.517 and 3.326，95% confidence intervals （CI） were 2.159-5.728 and 2.211-5.003，respectively]. Conclusions Serum Notch1 mRNA relative expression and Dickkopf-1 level are related to pembrolizumab therapeutic responsiveness，which can be used as effective indicators to evaluate therapeutic responsiveness.

Key words: Dickkopf-1, Notch1, Non-small cell lung cancer, Pembrolizumab, Therapeutic responsiveness

CLC Number:

R446.1

WANG Yafei, ZHANG Zhenjun, SONG Changliang, YANG Qiong. Roles of Notch1 mRNA and Dickkopf-1 in assessing the therapeutic responsiveness of pembrolizumab in non-small cell lung cancer patients[J]. Laboratory Medicine, 2024, 39(7): 627-633.

Figures/Tables 6

References 29

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基因名称	正向引物（5'~3'）	反向引物（5'~3'）
Notch1	GGTGAACTGCTCTGAGGAGATC	GGATTGCAGTCGTCCACGTTGA
GAPDH	TGATGGGTGTGAACCACGAG	CCCTTCCACGATGCCAAAGT

基因名称	正向引物（5'~3'）	反向引物（5'~3'）
Notch1	GGTGAACTGCTCTGAGGAGATC	GGATTGCAGTCGTCCACGTTGA
GAPDH	TGATGGGTGTGAACCACGAG	CCCTTCCACGATGCCAAAGT

组别	例数	Dickkopf-1/ （pg·mL-¹）	Notch1 mRNA
NSCLC组	169
治疗前		57.28±12.36*	3.91±0.73*
治疗3周		42.97±9.25*#	2.48±0.52*#
治疗6周		33.08±8.92*#△	1.71±0.46*#△
对照组	168	25.87±5.62	1.15±0.38

组别	例数	Dickkopf-1/ （pg·mL-¹）	Notch1 mRNA
NSCLC组	169
治疗前		57.28±12.36*	3.91±0.73*
治疗3周		42.97±9.25*#	2.48±0.52*#
治疗6周		33.08±8.92*#△	1.71±0.46*#△
对照组	168	25.87±5.62	1.15±0.38

组别	例数	性别			年龄/岁		吸烟史/ [例（%）]		肿瘤家族史/ [例（%）]	ECOG评分
组别	例数	男/[例（%）]	女/[例（%）]		年龄/岁		吸烟史/ [例（%）]		肿瘤家族史/ [例（%）]	0~1分/ [例（%）]	2分/ [例（%）]
PD组	42	27（64.29）	15（35.71）		70.73±5.42		17（40.48）		4（9.52）	22（52.38）	20（47.62）
DCR组	127	85（66.93）	42（33.07）		68.61±5.07		50（39.37）		38（90.48）	93（73.23）	34（26.77）
统计值		0.099			2.309		0.016		0	6.309
P值		0.753			0.022		0.899		0.989	0.012
组别	临床分期				肿瘤直径		病理类型
组别	Ⅲb期/ [例（%）]	Ⅳ期/ [例（%）]			<5 cm/ [例（%）]	≥5 cm/ [例（%）]	腺癌/ [例（%）]			鳞癌/ [例（%）]	其他/ [例（%）]
PD组	23（54.76）	19（45.24）			19（45.24）	23（54.76）	29（69.05）			10（23.81）	3（7.14）
DCR组	47（37.01）	80（62.99）			57（44.88）	70（55.12）	86（67.72）			31（24.41）	10（7.87）
统计值	4.1				0.002		0.035
P值	0.043				0.968		0.983
组别	淋巴转移/ [例（%）]	远隔转移/ [例（%）]			PD-L1			分化程度/[例（%）]
组别	淋巴转移/ [例（%）]	远隔转移/ [例（%）]			50％~89％/[例（%）]		≥90％/[例（%）]	低分化	中分化		高分化
PD组	21（50.00）	18（42.86）			32（76.19）		10（23.81）	8（19.05）	28（66.67）		6（14.29）
DCR组	87（68.50）	29（22.83）			72（56.69）		55（43.31）	14（11.02）	72（56.69）		41（32.28）
统计值	4.685	6.303			5.069			2.087
P值	0.03	0.012			0.024			0.037
组别	Dickkopf-1/（pg·mL^-1）						Notch1 mRNA
组别	治疗前	治疗3周		治疗6周			治疗前		治疗3周	治疗6周
PD组	68.05±14.27	48.62±9.81		38.94±9.03			4.45±0.76		2.89±0.55	2.11±0.43
DCR组	53.72±13.08	41.10±9.19		31.14±8.78			3.73±0.69		2.34±0.53	1.58±0.46
统计值	6.016	4.52		4.956			5.715		5.776	6.576
P值	<0.001	<0.001		<0.001			<0.001		<0.001	<0.001