前列腺癌

Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer
Clin Cancer Res. 2021 Jun 15;27(12):3478-3490. DOI: 10.1158/1078-0432.CCR-20-4217.

MRI 是诊断前列腺癌的重要工具。然而，这项技术大约有 15% 的具有临床意义的前列腺癌无法识别。在这里，作者使用单细胞空间蛋白组分析技术以及基因表达谱和基于 AI 的分析算法来探索这些肿瘤的生态系统。使用这些技术，作者揭示了前列腺肿瘤的深层分子、细胞和结构特征，以及与MRI诊断检查可见性的关联。

乳腺癌
Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response

Cancer Res. 2021 Dec 15;81(24):6196-6206. DOI: 10.1158/0008-5472.CAN-21-1079.

进入循环的肿瘤细胞通常是转移性癌症的前兆。此前，这项工作的作者发现这些细胞中的特定基因组区域经常受到拷贝数增加的影响，并利用这些信息来识别具有这种基因组特征的肿瘤——弥合了基因组学和空间生物学之间的差距。这项研究表明，这些所谓的循环肿瘤细胞 (CTC) 相关肿瘤在经过多轮治疗后的乳腺癌患者中更频繁地形成，并且往往表现出更高水平的空间异质性。单细胞空间蛋白组分析表明，这些异质性更高的肿瘤在三阴性乳腺癌中具有高度的 B 淋巴细胞浸润，这些数据显示了遗传亚克隆是如何产生的。

结肠癌

Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations

Mod Pathol. 2021 Nov 3. DOI: 10.1038/s41379-021-00953-0.

结直肠癌是一种高发病率和高死亡率的癌症。目前，术后化疗仅对少数患者有益，因此需要新的工具来筛查患者并识别风险增加的患者。基于数百名患者的组织样本，研究者使用单细胞空间蛋白组分析技术，试图揭示癌症治疗后生存的精细细胞决定因素。通过使用由单细胞空间蛋白组分析技术和独特的分析算法启用的多标志物分析，结果表明，特定 T 细胞亚型 PD-1 阴性 Treg 的募集与无病生存率高度相关。因此，肿瘤样本的多重成像和分析可能会提供一种未来的手段，将临床资源瞄准那些具有较高风险特征的患者。

黑色素瘤研究案例
Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma.

Cancer Immunol Res. 2022 Mar 1. DOI: 10.1158/2326-6066.CIR-21-1083.

癌症免疫疗法可以产生强大、持久的效果和肿瘤消退。然而，确定这些疗法最有效的患者和肿瘤仍然具有挑战性。在这项研究中，作者使用单细胞空间蛋白组分析技术来探索接受免疫治疗并表现出强烈反应的患者以及没有反应的患者的肿瘤细胞表型。

单细胞空间蛋白组分析技术开发相关文献

Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue

Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11982-7. DOI: 10.1073/pnas.1300136110.

A novel, automated technology for multiplex biomarker imaging and application to breast cancer
Histopathology 64(2), pp.242–255 (2014). DOI: 10.1111/his.12240

Microfluidic Tissue Mesodissection in Molecular Cancer Diagnostics
SLAS Technol. 2017 Aug;22(4):425–430. DOI: 10.1177/2211068216680208

Multi-modal imaging of histological tissue sections

IEEE International Symposium on Biomedical Imaging: From Nano to Macro pp. 288–291 (2008). DOI: 10.1109/ISBI.2008.4540989

肿瘤异质性研究案例

Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures
PLoS One. 2017 Nov 30;12(11):e0188878. DOI: 10.1371/journal.pone.0188878

Platform for Quantitative Evaluation of Spatial Intratumoral Heterogeneity in Multiplexed Fluorescence Images
Cancer Res. 2017 Nov 1;77(21):e71-e74. DOI: 10.1158/0008-5472.CAN-17-0676

Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity

JCI Insight. 2017 Jun 2;2(11):e93487. DOI: 10.1172/jci.insight.93487

Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers
J Pathol Inform. 2016 Nov 29;7:47. DOI: 10.4103/2153-3539.194839

Emerging understanding of multiscale tumor heterogeneity

Front Oncol. 2014 Dec 18; 2014;4:366. DOI: 10.3389/fonc.2014.00366

Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas

PLoS One. 2019 Dec 27;14(12):e0219724. DOI: 10.1371/journal.pone.0219724

肿瘤微环境与肿瘤免疫学研究案例

Robust single cell quantification of immune cell subtypes in histological samples

DOI: 10.1109/BHI.2017.7897220

Stromal-Based Signatures for the Classification of Gastric Cancer
Cancer Res. 2016 May 1;76(9):2573-86. DOI: 10.1158/0008-5472.CAN-16-0022

Multi-channel algorithm for segmentation of tumor blood vessels using multiplexed image data

Biomedical Imaging (ISBI), 2016 IEEE 13th International Symposium on (pp. 213–216). IEEE. DOI: 10.1109/ISBI.2016.7493247

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy

Cell. 2017 Sep 7;170(6):1109-1119.e10. DOI: 10.1016/j.cell.2017.08.027. Erratum in: Cell. 2018 Aug 9;174(4):1031-1032.

Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL
Cancer Immunol Res. 2019 Apr;7(4):644-657. DOI: 10.1158/2326-6066.CIR-18-0439

Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma
J Immunother Cancer. 2019 Oct 21;7(1):269. DOI: 10.1186/s40425-019-0723-9

Understanding heterogeneous tumor microenvironment in metastatic melanoma

PLoS One. 2019 Jun 5;14(6):e0216485. DOI: 10.1371/journal.pone.0216485

Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection
JHEP Reports. 2021 Oct 23. DOI: 10.1016/j.jhepr.2021.100388

Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study

J Immunother Cancer. 2021 Oct;9(10):e003476. DOI: 10.1136/jitc-2021-003476

癌症表征和预后研究案例
结肠癌

Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer
J Clin Invest. 2014 May;124(5):2172-87. DOI: 10.1172/JCI71103

The relative distribution of membranous and cytoplasmic met is a prognostic indicator in stage I and II colon cancer

Clin Cancer Res. 2008 Jun 15;14(12):3814-22. DOI: 10.1158/1078-0432.CCR-08-0180

Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo

Mol Syst Biol. 2015 Oct 30;11(10):835. DOI: 10.15252/msb.20156282. Erratum in: Mol Syst Biol. 2016 Aug 29;12(8):881.

Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations

Mod Pathol. 2021 Nov 3. DOI: 10.1038/s41379-021-00953-0  

前列腺癌

Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer

Clin Cancer Res. 2021 Jun 15;27(12):3478-3490. DOI: 10.1158/1078-0432.CCR-20-4217

霍奇金淋巴瘤

A single slide multiplex assay for the evaluation of classical Hodgkin lymphoma

Am J Surg Pathol. 2014 Sep;38(9):1193-202. DOI: 10.1097/PAS.0000000000000242

乳腺癌
Single-cell heterogeneity in ductal carcinoma in situ of breast

Mod Pathol. 2018 Mar;31(3):406-417. DOI: 10.1038/modpathol.2017.143

Multiplexed immunofluorescence delineates proteomic cancer cell states associated with metabolism

JCI Insight. 2016 May 5;1(6):e87030. DOI: 10.1172/jci.insight.87030

Taxonomy of breast cancer based on normal cell phenotype predicts outcome

J Clin Invest. 2014 Feb;124(2):859-70. DOI: 10.1172/JCI70941.

Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast

Br J Cancer. 2021 Mar;124(6):1150-1159. DOI: 10.1038/s41416-020-01216-6

Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response

Cancer Res. 2021 Dec 15;81(24):6196-6206. DOI: 10.1158/0008-5472.CAN-21-1079

胶质母细胞瘤

Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial

Sci Transl Med. 2019 Aug 14;11(505):eaaw5680. DOI: 10.1126/scitranslmed.aaw5680

发育生物学研究案例

Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut

Cell Syst. 2018 Jan 24;6(1):37-51.e9. DOI: 10.1016/j.cels.2017.10.012

神经系统疾病研究案例

Quantitative patterns of motor cortex proteinopathy across ALS genotypes

Acta Neuropathol Commun. 2020 Jul 2;8(1):98. DOI: 10.1186/s40478-020-00961-2