切换至 "中华医学电子期刊资源库"

中华医学超声杂志(电子版) ›› 2024, Vol. 21 ›› Issue (03) : 319 -326. doi: 10.3877/cma.j.issn.1672-6448.2024.03.011

泌尿生殖系统超声影像学

基于超声纹理影像转录组学预测前列腺癌
杨倩1, 李秋洋2, 李楠2, 罗渝昆2, 唐杰2,()   
  1. 1. 100142 北京,空军特色医学中心超声诊断科;100853 北京,解放军总医院第一医学中心超声诊断科
    2. 100853 北京,解放军总医院第一医学中心超声诊断科
  • 收稿日期:2023-03-27 出版日期:2024-03-01
  • 通信作者: 唐杰
  • 基金资助:
    国家自然科学基金(81801708); 中国博士后基金特别资助项目(2021T140795); 陕西省自然科学基础研究计划(2023-JC-QN-0912); 西安市科技计划项目(21YXYJ0134)

A radiotranscriptomics approach for prediction of prostate cancer based on ultrasound image texture features

Qian Yang1, Qiuyang Li2, Nan Li2, Yukunn Luo2, Jie Tang2,()   

  1. 1. Department of Ultrasound, Air Force Medical Center, PLA, Air Force Military Medical University, Beijing 100142, China;Department of Ultrasound, First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
    2. Department of Ultrasound, First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
  • Received:2023-03-27 Published:2024-03-01
  • Corresponding author: Jie Tang
引用本文:

杨倩, 李秋洋, 李楠, 罗渝昆, 唐杰. 基于超声纹理影像转录组学预测前列腺癌[J]. 中华医学超声杂志(电子版), 2024, 21(03): 319-326.

Qian Yang, Qiuyang Li, Nan Li, Yukunn Luo, Jie Tang. A radiotranscriptomics approach for prediction of prostate cancer based on ultrasound image texture features[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2024, 21(03): 319-326.

目的

探讨灰阶超声图像和超声造影图像的影像转录组学分析方法在前列腺结节良恶性预测诊断中的应用价值。

方法

分析2020年12月至2022年3月在解放军总医院第一医学中心接受超声引导下可疑前列腺癌进行穿刺活检的68例患者。患者均采用经直肠灰阶超声及超声造影2种显像模式,并对图像进行自动分割及纹理特征分析。活检标本进行RNA测序及前列腺癌相关的基因表达谱、功能富集和通路分析。绘制随机森林、贝叶斯和支持向量机3种数据集模型的受试者操作特征(ROC)曲线和校准曲线评价模型的预测效能。

结果

影像组学分析得到2个关键纹理特征:ca2-GLSZM-LZHGE和GLSZM-ZSV。RNA测序发现120个与前列腺癌相关的差异基因,利用影像转录组学方法得到区分前列腺癌和前列腺增生的生物标志物:ITGB3CAV1miR141-3plet-7a-5pmiR25-5pmiR200c-3p,功能富集和通路分析发现上述生物标志物与雄激素受体状态、耐药性、增殖和凋亡相关的转录组改变有关。随机森林、贝叶斯和支持向量机3种模型联合数据集ROC的曲线下面积(AUC)分别为0.99、0.98和0.99,3种模型影像组学数据集AUC分别为0.99、0.95和0.99,分别优于临床数据集AUC(0.79、0.85和0.92)及分子生物标志物数据集(转录组学)AUC(0.66、0.80和0.86)。联合数据集组模型ROC曲线和校准曲线均显示模型区分度和准确度良好。

结论

超声图像纹理特征在评估前列腺癌的生物标志物方面具有潜在的应用价值,并且基于超声图像构建的影像转录组学联合模型比影像组学模型具有更好的预测效能。

Objective

To evaluate the value of radiotranscriptomics analysis of gray-scale ultrasound images and contrast-enhanced ultrasound (CEUS) images in the diagnosis of benign and malignant prostate nodules.

Methods

A total of 68 patients who underwent ultrasound-guided biopsy for suspected prostate cancer (PCa) at the First Medical Center of Chinese PLA General Hospital from December 2020 to March 2022 were analyzed. All patients underwent transrectal gray-scale ultrasound and CEUS, and the images were automatically segmented and texture features were analyzed. Biopsy specimens were subjected to RNA sequencing and prostate cancer-related gene expression profiling as well as functional enrichment and pathway analysis. Random forest, Bayesian, and support vector machine (SVM) methods were used to draw the receiver operating characteristic (ROC) curve and calibration curve to evaluate the prediction efficiency of the model.

Results

Two key texture features, ca2-GLSZM-LZHGE and GLSZM-ZSV, were obtained by radiomics. RNA sequencing identified 120 differentially expressed genes related to PCa, and the biomarkers to distinguish PCa from benign prostatic hyperplasia (BPH) were obtained by correlation analysis: ITGB3, CAV1, miR141-3p, let-7a-5p, miR25-5p, and miR200c-3p. Functional enrichment and pathway analysis identified transcriptomic alterations associated with androgen receptor status, drug resistance, proliferation, and apoptosis. The area under the ROC curve (AUC) values of the three combined dataset models (random forest, naive Bayes, and SVM) and radiomics dataset models were 0.99, 0.98, and 0.99, and 0.99, 0.95, and 0.99, respectively, which were better than those of the clinical dataset models (0.79, 0.85, and 0.92) and molecular biomarker dataset (transcriptomics) models (0.66, 0.80, and 0.86). The ROC curve and calibration curve of the combined dataset group showed that the model had good discrimination and accuracy.

Conclusion

Ultrasound image texture features have potential application value in the evaluation of biomarkers of PCa, and the combined radiotranscriptomics model has better predictive efficiency than the radiomics model.

图1 前列腺肿瘤组织感兴趣区域手动勾画示意图。图a:前列腺癌灰阶超声图像;图b:前列腺癌超声造影图像;图c,d,e:前列腺癌手动勾画分割图像;图f:前列腺增生灰阶超声图像;图g:前列腺增生超声造影图像;图h,i,j:前列腺增生手动勾画分割图像
表1 前列腺癌及良性前列腺增生2组患者一般临床资料比较
图2 基于转录组学特征的前列腺癌评价模型。图a为Logistic回归模式,图b为随机森林模式,图c为支持向量机模式 注:CEUS为超声造影,B-mode为灰阶超声
图3 超声图像纹理特征相关差异基因功能与表达。图a:网络图显示灰阶超声图像和超声造影纹理特征调节mRNA及miRNA相关的主要富集的功能和KEGG通路(绿色代表mRNA,红色代表miRNA,蓝色代表功能,紫色代表通路);图b:热图及火山图显示根据关键纹理特征有2个显著差异表达的mRNA;CAV1和ITGB3(P<0.05),上端热图中橙色代表前列腺癌患者,蓝色代表良性前列腺增生患者,橙色代表差异基因上调,蓝色代表差异基因下调;下端火山图中粉色代表上调基因,绿色代表下调基因。图c:热图及火山图显示关键纹理特征有4个显著差异表达miRNAmiR141-3plet-7a-5pmiR25-5pmiR200c-3pP<0.05)。上端热图中橙色代表前列腺癌患者,蓝色代表良性前列腺增生患者,橙色代表差异miRAN上调,蓝色代表差异miRAN下调;下端火山图中粉色代表上调miRAN,绿色代表下调miRAN
图4 3种机器学习模式下不同指标预测甲状腺癌的受试者操作特征曲线及校准曲线。图a~c:随机森林(random forest)、贝叶斯(Naïve Byes)和支持向量机(support vector machine)模式下使用临床特征(Clinical data)、转录组学特征(Transcriptomics)、影像组学(Radiomics)特征和联合特征(Combination)预测前列腺癌的表现;图d为校准曲线
1
Zhu Y, Mo M, Wei Y, et al. Epidemiology and genomics of prostate cancer in Asian men [J]. Nat Rev Urol, 2021, 18(5): 282-301.
2
Buchser D, Medina R, Mayrata E, et al. Salvage local treatment for localized radio-recurrent prostate cancer: a narrative review and future perspectives [J]. Future Oncol, 2021, 17(31): 4207-4219.
3
梁梓南, 杨薇. 影像及影像组学评价肝细胞癌微血管侵犯的应用现状[J/OL].中华医学超声杂志(电子版), 2022, 19(9): 1003-1007.
4
Lin F, Wang Z, Zhang K, et al. Contrast-Enhanced Spectral Mammography-Based Radiomics Nomogram for Identifying Benign and Malignant Breast Lesions of Sub-1 cm [J]. Front Oncol, 2020, 10: 573630.
5
Fan L, Cao Q, Ding X, et al. Radiotranscriptomics signature-based predictive nomograms for radiotherapy response in patients with nonsmall cell lung cancer: combination and association of CT features and serum miRNAs levels [J]. Cancer Med, 2020, 9(14): 5065-5074.
6
Dinis C, Schaap A, Kant J, et al. Radiogenomics analysis linking multiparametric MRI and transcriptomics in prostate cancer [J]. Cancers (Basel), 2023, 15(12): 3074.
7
Sun, Y, Williams S, Byrne D, et al. Association analysis between quantitative MRI features and hypoxia-related genetic profiles in prostate cancer: a pilot study [J]. Br J Radiol, 2019, 92(1104): 20190373.
8
Dwivedi DK, Jagannathan NR. Emerging MR methods for improved diagnosis of prostate cancer by multiparametric MRI [J]. Magma, 2022, 35(4): 587-608.
9
Ou W, Lei J, Li M, et al. Ultrasound-based radiomics score for pre-biopsy prediction of prostate cancer to reduce unnecessary biopsies [J]. Prostate, 2023, 83(1): 109-118.
10
Fornacon-Wood I, Mistry H, Ackermann CJ, et al. Reliability and prognostic value of radiomic features are highly dependent on choice of feature extraction platform [J]. Eur Radiol, 2020, 30(11): 6241-6250.
11
Fischer S, Tahoun M, Klaan B, et al. Radiogenomic approach for decoding molecular mechanisms underlying tumor progression in prostate cancer [J]. Cancers (Basel), 2019, 11(9): 1293.
12
Lambin P, Rios-Velazquez E, Leijenaar R, et al. Radiomics: extracting more information from medical images using advanced feature analysis [J]. Eur J Cancer, 2012, 48(4): 441-446.
13
Fei B, Schuster DM, Master V, et al. A molecular image-directed, 3D ultrasound-guided biopsy system for the prostate [J]. Proc Spie Int Soc Opt Eng, 2012, 2012: 831613.
14
Zhang Y, Sankar R, Qian W. Boundary delineation in transrectal ultrasound image for prostate cancer [J]. Comput Biol Med, 2007, 37(11): 1591-1599.
15
Zhang Q, Xiong J, Cai Y, et al. Multimodal feature learning and fusion on B-mode ultrasonography and sonoelastography using point-wise gated deep networks for prostate cancer diagnosis [J]. Biomed Tech (Berl), 2020, 65(1): 87-98.
16
Li M, Chen T, Zhao W, et al. Radiomics prediction model for the improved diagnosis of clinically significant prostate cancer on biparametric MRI [J]. Quant Imaging Med Surg, 2020, 10(2): 368-379.
17
Sun Y, Reynolds HM, Wraith D, et al. Automatic stratification of prostate tumour aggressiveness using multiparametric MRI: a horizontal comparison of texture features [J]. Acta Oncol, 2019, 58(8): 1118-1126.
18
O'Reilly D, Downing T, Kouba S, et al. CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer [J]. Cell Calcium, 2022, 103: 102554.
19
Ariotti N, Wu Y, Okano S, et al. An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells [J]. Autophagy, 2021, 17(9): 2200-2216.
20
Patel R, Ford CA, Rodgers L, et al. Cyclocreatine suppresses creatine metabolism and impairs prostate cancer progression [J]. Cancer Res, 2022, 82(14): 2565-2575.
21
Gu Y, Lei D, Qin X, et al. Integrated analysis reveals together miR-182, miR-200c and miR-221 can help in the diagnosis of prostate cancer [J]. PLoS One, 2015, 10(10): e0140862.
22
Li JZ, Li J, Wang HQ, et al. MiR-141-3p promotes prostate cancer cell proliferation through inhibiting kruppel-like factor-9 expression [J]. Biochem Biophys Res Commun, 2017, 482(4): 1381-1386.
23
Ghorbanmehr N, Gharbi S, Korsching E, et al. miR-21-5p, miR-141-3p, and miR-205-5p levels in urine-promising biomarkers for the identification of prostate and bladder cancer [J]. Prostate, 2019, 79(1): 88-95.
24
Tang G, Du R, Tang Z, et al. MiRNALet-7a mediates prostate cancer PC-3 cell invasion, migration by inducing epithelial-mesenchymal transition through CCR7/MAPK pathway [J]. J Cell Biochem, 2018, 119(4): 3725-3731.
25
Liu H, Chen W, Zhi X, et al. Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility [J]. Oncogene, 2018, 37(36): 4964-4978.
26
Tsao CW, Liu CY, Cha TL, et al. Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population [J]. J Chin Med Assoc, 2014, 77(10): 513-518.
[1] 曾晴, 文华轩, 袁鹰, 廖伊梅, 秦越, 罗丹丹, 梁美玲, 彭桂艳, 林毅, 谭莹, 温昕, 黄文兰, 李胜利. 胎儿颅脑五横切面法的临床应用[J]. 中华医学超声杂志(电子版), 2024, 21(03): 243-250.
[2] 尹宏宇, 吴青青, 李晓菲. 颈后透明层和头臀长在妊娠11~13+6周双胎心脏畸形筛查中的价值[J]. 中华医学超声杂志(电子版), 2024, 21(03): 251-256.
[3] 朱惠娟, 邝海燕, 骆迎春, 邓光祁, 蒋凌晖, 汪圣, 王政, 孔一凡, 龙煜. 胎儿脐-门-体静脉系统异常分流的产前超声诊断及产后结局[J]. 中华医学超声杂志(电子版), 2024, 21(03): 257-267.
[4] 张焱, 刘春媚, 姚瑾, 陈苗苗, 徐雯, 黄品同. 超声O-RADS分类和临床特征对不同病理类型卵巢浆液性肿瘤的诊断价值[J]. 中华医学超声杂志(电子版), 2024, 21(03): 268-274.
[5] 谢峰, 伍玉晗, 赵胜, 杨小红, 王玉波, 石珍, 范建华, 章敏. 产前超声和MRI诊断胎儿硬脑膜窦畸形的联合应用[J]. 中华医学超声杂志(电子版), 2024, 21(03): 275-280.
[6] 徐燕, 茹彤, 郑明明, 顾燕, 朱湘玉, 严陈晨, 陈玲, 戴晨燕. Miller-Dieker综合征胎儿产前超声、磁共振影像学特征及遗传学分析[J]. 中华医学超声杂志(电子版), 2024, 21(03): 281-287.
[7] 马旦杰, 黄品同, 徐琛, 周芳芳, 潘敏强. 超声造影LI-RADS系统联合甲胎蛋白对有无高危因素背景人群肝细胞癌的诊断价值[J]. 中华医学超声杂志(电子版), 2024, 21(03): 288-296.
[8] 罗敏华, 王文平, 孔文韬. 肝脏炎性假瘤的超声造影表现及其诊断价值[J]. 中华医学超声杂志(电子版), 2024, 21(03): 297-303.
[9] 伯小皖, 郭乐杭, 余松远, 李明宙, 孙丽萍. 甲状腺结节人工智能自动分割和分类系统的建立和验证[J]. 中华医学超声杂志(电子版), 2024, 21(03): 304-309.
[10] 曹琨芃, 王昕玥, 吴柳希, 邓红艳, 李璐, 徐超丽, 叶新华. 淋巴瘤患者超声引导下颈内静脉置管术后静脉血栓形成的危险因素评估[J]. 中华医学超声杂志(电子版), 2024, 21(03): 310-318.
[11] 张胜男, 苗雅敬, 周虹, 韩高洁, 王静, 仝巧立, 张旭倩, 尹洪宁. 左心耳三维经食管超声测量与Watchman左心耳封堵器大小的相关性研究[J]. 中华医学超声杂志(电子版), 2024, 21(02): 107-113.
[12] 刘韩, 王胰, 舒庆兰, 彭博, 尹立雪, 谢盛华. 基于深度学习的超声心动图三尖瓣反流严重程度智能评估方法研究[J]. 中华医学超声杂志(电子版), 2024, 21(02): 121-127.
[13] 金从稳, 陈霖霖, 刘浩, 余有声, 陈本鑫. 超声联合细针穿刺定位在乳腺微小病灶切除中的应用研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 423-426.
[14] 邢益民, 张天飞, 戴慧勇. 胃肠充盈超声造影检查在反酸、嗳气患者临床诊断中的应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(03): 303-306.
[15] 王伟利, 唐流康, 陈明政, 谢峰. 超声检查在肝胆外科中的应用[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 265-269.
阅读次数
全文


摘要