Application of PET/CT radiomics combined with LncRNA-DGCR5 in precision medicine of NSCLC

doi:10.11958/20221865

Abstract

Abstract:

Objective To study the application value of PET/CT radiomics combined with long noncoding RNA DiGeorge syndrome critical region gene 5 (LncRNA-DGCR5) in the precision medicine of non-small cell lung cancer (NSCLC). Methods A total of 106 NSCLC patients received PET/CT examination and chemoradiotherapy, and their efficacy was evaluated according to the Evaluation Criteria for Solid Tumor Efficacy after Treatment (RECIST). Patients with complete remission and partial remission were included in the response group (58 cases), and patients with stable or progressive disease were included in the non-response group (48 cases). Image texture parameters of PET/CT including SUV_max (maximum standard value), mean value, variance, kurtosis, skewness, contrast, entropy and energy were compared between groups. Real-time fluorescence quantitative PCR was used to detect LncRNA-DGCR5 expression in peripheral blood. Receiver operating characteristic curve (ROC) was constructed to analyze the predictive value of each index to the therapeutic efficacy of NSCLC patients. Results The SUV_max value, entropy and expression of LncRNA-DGCR5 were significantly lower in the response group than those in the non-response group (P<0.05), and the energy was significantly higher in the response group than that in the non-response group (P<0.05). There were no significant differences in the other parameters between the two groups. Patients were divided into the low LncRNA-DGCR5 expression group (51 cases) and the high LncRNA-DGCr5 expression group (55 cases) according to the mean expression of LncRNA-DGCR5 (2.01) as the critical value. Compared with the low LncRNA-DGCR5 expression group, the PET/CT image texture parameters of SUV_max and entropy were significantly increased in the high LncRNA-DGCR5 expression group, and the energy was significantly decreased (P<0.05). ROC curve construction showed that the AUCs of SUV_max value, entropy, energy and LncRNA-DGCR5 expression on predicting the treatment efficacy of patients with NSCLC were 0.897, 0.851, 0.795 and 0.949 respectively, and the AUC of combined prediction was the highest at 0.998. Conclusion PET/CT radiomics combined with LncRNA-DGCR5 is helpful to predict the treatment efficacy of patients with NSCLC, thus providing the guidance for precision medicine of NSCLC.

Key words: carcinoma, non-small-cell lung, tomography, emission-computed, RNA, Long Noncoding, DiGeorge syndrome critical region gene 5, precision medicine

CLC Number:

R734.2，R814.42

Figures/Tables 5

References 20

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics,2020[J]. CA Cancer J Clin, 2020, 70(1):7-30. doi:10.3322/caac.21590.
[2]	ALEXANDER M, KIM S Y, CHENG H. Update 2020:Management of non-small cell lung cancer[J]. Lung, 2020, 198(6):897-907. doi:10.1007/s00408-020-00407-5.
[3]	郑庆中, 苏洁敏, 邓菁, 等. ¹⁸F-FDG PET/CT代谢参数对116例非小细胞肺癌患者预后评估价值[J]. 中华肿瘤防治杂志, 2020, 27(16):1309-1314.
	ZHENG Q Z, SU J M, DENG J, et al. Prognostic value of ¹⁸F-FDG PET/CT metabolic parameters in patients with non-small cell lung cancer[J]. Chin J Cancer Prev Treat, 2020, 27(16):1309-1314. doi:10.16073/j.cnki.cjcpt.2020.16.06.
[4]	刘寒冰, 赵杰, 胡春峰. PET/CT代谢参数及纹理分析评价晚期肺腺癌EGFR-TKI的疗效[J]. 中国医学影像学杂志, 2020, 28(11):842-845.
	LIU H B, ZHAO J, HU C F. Evaluation of EGFR-TKI in advanced lung adenocarcinoma by PET/CT metabolic parameters and texture analysis[J]. Chinese Journal of Medical Imaging, 2020, 28(11):842-845. doi:10.3969/j.issn.1005-5185.2020.11.011.
[5]	SHEN Y, LIN Y, LIU K, et al. XIST:A meaningful long noncoding RNA in NSCLC process[J]. Curr Pharm Des, 2021, 27(11):1407-1417. doi:10.2174/1381612826999201202102413.
[6]	XUE C, CHEN C, GU X, et al. Progress and assessment of lncRNA DGCR5 in malignant phenotype and immune infiltration of human cancers[J]. Am J Cancer Res, 2021, 11(1):1-13.
[7]	WANG J, SHU H Z, XU C Y, et al. LncRNA DGCR5 promotes non-small cell lung cancer progression via sponging miR-218-5p[J]. Eur Rev Med Pharmacol Sci, 2020, 24(20):10303. doi:10.26355/eurrev_202010_23355.
[8]	周洁, 周清华. NTRK基因融合和TRK抑制剂在非小细胞肺癌中的研究进展[J]. 中国肿瘤临床, 2020, 47(12):633-636.
	ZHOU J, ZHOU Q H. Role of NTRK gene fusions and TRK inhibitors in non-small cell lung cancer[J]. Chin J Clin Oncol, 2020, 47(12):633-636. doi:10.3969/j.issn.1000-8179.2020.12.497.
[9]	EZE C, SCHMIDT-HEGEMANN N S, SAWICKI L M, et al. PET/CT imaging for evaluation of multimodal treatment efficacy and toxicity in advanced NSCLC-current state and future directions[J]. Eur J Nucl Med Mol Imaging, 2021, 48(12):3975-3989. doi:10.1007/s00259-021-05211-8.
[10]	刘寒冰, 赵杰, 胡春峰, 等. PET/CT纹理分析在预测非小细胞肺癌EGFR基因突变中的应用[J]. 临床放射学杂志, 2020, 39(9):1759-1763.
	LIU H B, ZHAO J, HU C F. The application of PET/CT combined texture analysis in predicting EGFR gene mutation in non-small cell lung cancer[J]. J Clin Radiol, 2020, 39(9):1759-1763. doi:10.13437/j.cnki.jcr.2020.09.018.
[11]	AGÜLOĞLU N, AKYOL M, KÖMEK H, et al. The prognostic value of ¹⁸F-FDG PET/CT metabolic parameters in predicting treatment response before EGFR TKI treatment in patients with advanced lung adenocarcinoma[J]. Mol Imaging Radionucl Ther, 2022, 31(2):104-113. doi:10.4274/mirt.galenos.2022.24650.
[12]	张晓洁, 李娜, 杨芳, 等. ¹⁸F-FDG PET/CT技术评价T2DM对晚期结直肠癌患者PD-L1治疗疗效的影响[J]. 影像科学与光化学, 2022, 40(2):237-242.
	ZHANG X J, LI L, YANG F, et al. The value of ¹⁸F-FDG PET/CT technology in evaluating the effect of T2DM on the efficacy of PD-L1 targeted therapy in patients with advanced colorectal cancer[J]. Imag Sci Photochem, 2022, 40(2):237-242. doi:10.7517/issn.1674-0475.210831.
[13]	EVANGELISTA L, SEPULCRI M, PASELLO G. PET/CT and the response to immunotherapy in lung cancer[J]. Curr Radiopharm, 2020, 13(3):177-184. doi:10.2174/1874471013666191220105449.
[14]	SUN X Y, CHEN T X, CHANG C, et al. SUVmax of ¹⁸FDG PET/CT predicts histological grade of lung adenocarcinoma[J]. Acad Radiol, 2021, 28(1):49-57. doi:10.1016/j.acra.2020.01.030.
[15]	任树华, 黄琪, 胡静超, 等. ¹⁸F-AV45 PET显像在轻微认知下降和轻度认知障碍患者中的应用[J]. 中华核医学与分子影像杂志, 2020, 40(4):196-200.
	REN S H, HUANG Q, HU J C, et al. Application of ¹⁸F-AV45 PET imaging in subtle cognitive decline and mild cognitive impairment patients[J]. Chinese Journal of Nuclear Medicine and Molecular Imaging, 2020, 40(4):196-200. doi:10.3760/cma.j.cn321828-20190812-00166.
[16]	张斌, 马玉波, 耿彦方, 等. ¹⁸F-FDG PET/CT图像纹理分析在非小细胞肺癌中的应用价值[J]. 临床放射学杂志, 2019, 38(10):1852-1856.
	ZHANG B, MA Y B, GENG Y F, et al. The value of ¹⁸F-FDG PET/CT texture analysis in non-small cell lung cancer[J]. J Clin Radiol, 2019, 38(10):1852-1856. doi:10.13437/j.cnki.jcr.2019.10.013.
[17]	段玉青, 王梦杰, 王洪琰, 等. lncRNA DGCR5在食管鳞状细胞癌组织中的表达及其临床意义[J]. 中国肿瘤生物治疗杂志, 2020, 27(4):416-419.
	DUAN Y Q, WANG M J, WANG H Y, et al. Expression of lncRNA DGCR5 in esophageal squamous cell carcinoma tissues and its clinical significance[J]. Chinese Journal of Cancer Biotherapy, 2020, 27(4):416-419. doi:10.3872/j.issn.1007-385x.2020.04.012.
[18]	籍玉青, 尹永波, 邱金霞. lncRNA DGCR5通过靶向调控miR-21抑制鼻咽癌细胞的增殖、侵袭和迁移[J]. 中国老年学杂志, 2022, 42(11):2791-2795.
	JI Y Q, YIN Y B, QIU J X. lncRNA DGCR5 inhibition of proliferation, invasion and migration of nasopharyngeal carcinoma cells through targeted regulation of miR-21[J]. Chinese Journal of Gerontology, 2022, 42(11):2791-2795. doi:10.3969/j.issn.1005-9202.2022.11.055.
[19]	KANG M, SHI J, LI B, et al. LncRNA DGCR5 regulates the non-small cell lung cancer cell growth,migration,and invasion through regulating miR-211-5p/EPHB6 axis[J]. Biofactors, 2019, 45(5):788-794. doi:10.1002/biof.1539.
[20]	郭水根, 舒慧珍. 沉默长链非编码RNA DGCR5对肺腺癌细胞增殖、侵袭、迁移及Wnt/β-catenin信号通路的影响[J]. 中国免疫学杂志, 2020, 36(23):2866-2871.
	GUO S G, SHU H Z. Effects of silencing long non-coding RNA DGCR5 on proliferation,invasion,migration and Wnt/β-catenin signaling pathway in lung adenocarcinoma cells[J]. Chinese Journal of Immunology, 2020, 36(23):2866-2871. doi:10.3969/j.issn.1000-484X.2020.23.011.

组别	n		性别				年龄
组别	n		男		女		<60岁		≥60岁
无反应组	48		25（52.08）		23（47.92）		20（41.67）		28（58.33）
有反应组	58		34（58.62）		24（41.38）		26（44.83）		32（55.17）
χ²			0.455				0.107
组别		肿瘤最大径				吸烟史
组别		≤5 cm		>5 cm		有		无
无反应组		23（47.92）		25（52.08）		27（56.25）		21（43.75）
有反应组		36（62.07）		22（37.93）		26（44.83）		32（55.17）
χ²		2.131				1.371
组别		肿瘤部位				病理类型
组别		中央型		周围型		鳞癌		腺癌
无反应组		28（58.33）		20（41.67）		20（41.67）		28（58.33）
有反应组		40（68.97）		18（31.03）		31（53.45）		27（46.55）
χ²		1.291				1.460

组别	n		性别				年龄
组别	n		男		女		<60岁		≥60岁
无反应组	48		25（52.08）		23（47.92）		20（41.67）		28（58.33）
有反应组	58		34（58.62）		24（41.38）		26（44.83）		32（55.17）
χ²			0.455				0.107
组别		肿瘤最大径				吸烟史
组别		≤5 cm		>5 cm		有		无
无反应组		23（47.92）		25（52.08）		27（56.25）		21（43.75）
有反应组		36（62.07）		22（37.93）		26（44.83）		32（55.17）
χ²		2.131				1.371
组别		肿瘤部位				病理类型
组别		中央型		周围型		鳞癌		腺癌
无反应组		28（58.33）		20（41.67）		20（41.67）		28（58.33）
有反应组		40（68.97）		18（31.03）		31（53.45）		27（46.55）
χ²		1.291				1.460

组别	n	SUV_max	平均值	方差	峰度	偏度	对比度	熵	能量	LncRNA-DGCR5
无反应组	48	13.61±3.37	296.37±58.51	132.55±28.92	0.92±0.33	-0.11±0.07	2.27±0.41	0.73±0.25	0.89±0.26	3.13±0.87
有反应组	58	6.86±2.45	314.93±72.04	126.80±23.16	0.84±0.21	-0.13±0.08	2.39±0.53	0.35±0.19	1.25±0.33	1.09±0.74
t		11.920^＊＊	1.435	1.137	1.513	1.355	1.283	8.886^＊＊	6.142^＊＊	13.046^＊＊

组别	n	SUV_max	平均值	方差	峰度	偏度	对比度	熵	能量	LncRNA-DGCR5
无反应组	48	13.61±3.37	296.37±58.51	132.55±28.92	0.92±0.33	-0.11±0.07	2.27±0.41	0.73±0.25	0.89±0.26	3.13±0.87
有反应组	58	6.86±2.45	314.93±72.04	126.80±23.16	0.84±0.21	-0.13±0.08	2.39±0.53	0.35±0.19	1.25±0.33	1.09±0.74
t		11.920^＊＊	1.435	1.137	1.513	1.355	1.283	8.886^＊＊	6.142^＊＊	13.046^＊＊

组别	n	SUV_max	平均值	方差	峰度	偏度	对比度	熵	能量
LncRNA-DGCR5低表达组	51	6.76±2.46	314.09±67.21	125.25±22.84	0.86±0.23	-0.11±0.06	2.36±0.48	0.31±0.14	1.35±0.28
LncRNA-DGCR5高表达组	55	12.84±3.45	299.51±62.48	133.26±29.71	0.89±0.32	-0.13±0.08	2.31±0.42	0.72±0.26	0.84±0.25
t		10.374^＊＊	1.157	1.547	0.550	1.447	0.572	9.996^＊＊	9.906^＊＊