Advances in single-cell RNA sequencing and its applications in cancer research

Huang, Dezhi; Ma, Naya; Li, Xinlei; Gou, Yang; Duan, Yishuo; Liu, Bangdong; Xia, Jing; Zhao, Xianlan; Wang, Xiaoqi; Li, Qiong; Rao, Jun; Zhang, Xi

doi:10.1186/s13045-023-01494-6

Journal of Hematology & Oncology

Table 4 Clinical significance of scRNA-seq in various solid tumors

From: Advances in single-cell RNA sequencing and its applications in cancer research

Tumor	Year	Species	Protocol	Accession number (custom database if available)	Clinical significance	References
Lung cancer	2021	Human	10 × Genomics	Correspondence with authors	Provided single-cell transcriptomic profiles of SSNs and their TME that helped advance lung cancer immunotherapy	[252]
	2022	Mouse	10 × Genomics	GSE180963; GSE182228	ICAM1 on tumor cells orchestrates antitumor immune response, especially in adaptive immunity	[159]
	2023	Human	BD Rhapsody Single-Cell Analysis System	HRA001033	Neoadjuvant PD-1 blockade combined with chemotherapy was associated with the emergence of distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response	[160]
Colorectal Cancer	2020	Human	Smart-seq2	PRJEB34105; GSE146771	Two distinct TAM subsets showed inflammatory and angiogenic signatures, and showed differential sensitivity to CSF1R blockade. Anti-CD40 therapy activated specific cDC1s and expanded Th1-like and CD8⁺ memory T cells	[163]
	2020	Human	STRT-seq	HRA000201	SCNAs were prevalent in immune cells, fibroblasts, and endothelial cells in the TME of CRC, and the proportion of SCNA fibroblasts in tumor was much higher than that in normal tissue. There was clonal expansion of fibroblasts with SCNAs in the tumor, especially the tumors with chr7 gain	[114]
	2021	Mouse	10 × Genomics	SUB8983993	The intratumoral immunomodulation induced by CD73 inhibition is distinct from that induced by PD-1 inhibition, and agents inhibiting CD73 have potential as novel anticancer immunotherapies for CRC that may have synergistic effects when combined with PD-1 blockade treatments	[166]
	2021	Human	SMART seq v4	PRJNA759644	Identified 59 single CTCs which were classified into four groups based on EMT and stem cell-related gene expression. Patients receiving second or later-line treatment who had CTCs expressing EMT genes had significantly shorter PFS and OS	[119]
	2021	Human	10 × Genomics	Correspondence with authors	Tumor mutational burden was associated with distinct immune profile patterns in human CRC. Identified phenotypic and functional diversity of tumor-associated macrophages and T cells	[253]
	2022	Human	Modified STRT-seq protocol and SMART-seq2	HRA000183	Provided insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy	[162]
Gastric cancer	2021	Human	Smart-seq2	GSE158631	Discovered gastric cancer lymph node metastasis marker genes (ERBB2, CLDN11, and CDK12), as well as potential gastric cancer evolution-driving genes (FOS and JUN)	[168]
	2022	Human	10 × Genomics	Correspondence with authors	PD-1 expression in CD8⁺ T cells might predict clinical responses to PD-1 blockade therapy in gastric cancer	[254]
	2022	Human	10 × Genomics	HRA002336; GSE206785	Revealed 81 well-defined TME cell types from nonepithelial origin, and these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells established an immunosuppressive microenvironment that correlated with worse prognosis and lack of response in anti-PD1-treated patients	[171]
	2022	Human	10 × Genomics	GSE183904	Identified increased plasma cell proportions as a novel feature of diffuse-type tumors, and uncovered distinct CAF subtypes with INHBA-FAP-high cell populations as predictors of poor clinical prognosis	[110]
	2022	Human	10 × Genomics	Correspondence with authors	iCAFs and eCAFs not only exhibited enhanced pro-invasive activities but also mobilized surrounding immune cells to construct a tumor-favorable microenvironment	[109]
	2022	Human	10 × Genomics	PRJCA002596	Tregs were significantly enriched in gastric tumor tissues with increased expression of immune suppression related genes. ACKR1 was specifically expressed in tumor endothelial cells, and high ACKR1 expression was associated with poor prognosis in the cohort data, potentially revealing a novel target for gastric cancer treatment	[139]
	2022	Human	10 × Genomics	PRJNA776683	Abnormal neutrophil polarization and maturation and activation of the immune checkpoint SPP1 might contribute to LN metastasis in gastric cancer	[169]
Liver cancer	2018	Human	10 × Genomics	GSE103591	Different CSC subpopulations had distinct molecular signatures, and distinct genes within different CSC subpopulations were independently associated with HCC prognosis	[123]
	2022	Human	10 × Genomics	EGAS00001004843	Identified early predictors of clinical response to anti-PD-1 ICB in patients with HCC, and proposed a new combination immunotherapy of anti-PD-1 and anti-TNFR2 for HCC that may enhance response without exacerbating irAEs	[255]
	2022	Mouse	10 × Genomics	GSE212047	The dynamic shift in HSC subpopulations and their mediators during chronic liver disease is associated with a switch from protection against HCC to HCC promotion	[173]
	2022	Human	BD Rhapsody platform	Correspondence with authors	Revealed B-cell-driven type 2 innate inflammation and a potential strategy for HCC immunotherapy	[174]
	2022	Human	10 × Genomics	OEP002779	FACT inhibition was identified as a promising epigenetic-targeted therapeutic strategy	[82]
	2022	Mouse	10 × Genomics	GSE181515	Depletion of Prom1⁺ cells impeded tumor growth and reduced cancer hallmarks. The Prom1-lineage gene signature predicted poor prognosis in HCC, and enrichment of reactive oxygen species detoxification genes was key for lineage propagation	[178]
	2023	Mouse	10 × Genomics	PRJNA825069	Single anti-PD-1 treatment appears to be effective in HCCs with genetic mutations driving hot tumors, while combined anti-PD-1 and sorafenib treatment may be more appropriate in HCCs with genetic mutations driving cold tumors	[175]
Breast cancer	2020	PDX models	SmartSeq2	GSE123837	Pharmacological inhibition of OXPHOS dramatically attenuated metastatic seeding in the lungs, revealing the potential of targeting OXPHOS to prevent metastatic spread in patients with breast cancer	[74]
	2021	Human	10 × Genomics	Correspondence with authors	Basal-like breast cancer (ER^neg) might originate from luminal progenitors, and ER^high luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers	[180]
	2021	Mouse	Fluidigm C1 platform	GSE148614	BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anticancer drugs at the intertumor level and reconstructed the BRCA1 related mammary tumorigenesis to uncover transcriptomes alterations	[181]
	2023	Human and mouse	10 × Genomics	GSE190772; GSE210286	The combination of a p38i, anti-OX40 therapy, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory	[182]
Esophageal cancer	2021	Human	10 × Genomics	PRJNA777911	Identified a tumor-specific subset of CST1⁺ myofibroblasts with prognostic value, potential biological significance, and cancer-specific expression of immune checkpoint inhibitors	[86]
	2021	Human	10 × Genomics	GSE160269	The expression levels of the identified 14 genes were significantly associated with survival time in ESCC patients	[187]
Ovarian cancer	2021	Human	10 × Genomics	GSE147082	TOX-expressing CD8⁺ Trm and granulysin-expressing CD4⁺ T-cell clusters were enriched in the high T_inf group. The high T_inf group had an antitumor response	[256]
	2021	Human	10 × Genomics	EGAS00001004987	High relative frequencies of myofibroblasts, TGF-β-driven CAFs, mesothelial cells, and lymphatic endothelial cells predicted poor outcomes, while a high frequency of plasma cells correlated with a more favorable outcome	[192]
	2022	Human	10 × Genomics	PRJCA009148	Expression of the ERBB2 and HOXB-AS3 genes was higher in metastatic tumors than in primary tumors. CAFs with EMT-program were enriched in HG_M	[189]
	2022	Human	10 × Genomics	DRA012826; DRA012827	A cancer-initiating cell population and a population expressing CA125 survived initial treatment, suppressed antitumor immunity, and were associated with poor prognosis	[193]
	2022	Human	10 × Genomics	GSE184880	Identification of a model including four EMT-related genes for the prediction of HGSOC patient outcomes, the role of mCAFs in enhancing ovarian cancer cell invasion, and the potential therapeutic value of anti-TIGIT treatment	[108]
	2022	Human	10 × Genomics	EGAS00001005010	Identification of a consistent increase in the stress-associated cell state during chemotherapy. The stress-associated state existed before chemotherapy, was subclonally enriched during the treatment, and was associated with poor PFS	[257]
Melanoma	2018	Human	Smart-seq2	GSE115978	Identified a resistance program expressed by malignant cells that was associated with T-cell exclusion and immune evasion. CDK4/6 inhibitors repressed the program and might sensitize melanoma to immunotherapy	[142]
	2018	Human	Smart-seq2	phs001680.v1.p1; GSE120575	Revealed distinct CD45⁺ cells associated with clinical outcome. The balance between two CD8⁺ T-cell states was linked with tumor regression. TCF7⁺CD8⁺ T-cell frequency in tumor tissue predicted response and better survival. Dual blockade of CD39 and different checkpoint proteins enhanced immunity	[258]
	2020	Human	10 × Genomics	GSE139829	LAG3 was identified as a potential candidate for immune checkpoint blockade in patients with high-risk UM	[94]
	2021	Human	10 × Genomics	GSE138665	Revealed a gene regulatory network underlying an invasive state and poor prognosis driven in part by the transcription factor HES6. HES6 was identified as a valid target to stop uveal melanoma progression	[81]
	2021	Human	10 × Genomics	Correspondence with authors	Provided the first atlas of two distinct sites of melanoma CNS metastases and defined the immune cell landscape. Identified the presence of a rare population of DCs that was associated with increased OS	[259]
	2021	Human	10 × Genomics	phs002944.v1.p1; GSE185386	Chromosomal instability is associated with brain metastasis. Cancer cells in the brain metastases were enriched for a neuronal-like metaprogram. Macrophages had a pro-tumorigenic phenotype in brain metastases	[260]
	2022	Human	Smart-seq2	Correspondence with authors	Melanoma CTCs could be served as biomarkers for disease monitoring	[120]
	2022	Mouse	10 × Genomics	GSE211602	ASNS overexpression enhanced CD8⁺ T-cell effector function and antitumor responses	[147]
	2023	Human	10 × Genomics	EGAS00001005580	The highest LAG3 expression was noted in NK cells, Tregs, and CD8⁺ T cells, and these cell populations underwent the most significant changes during treatment. LAG3⁺ Tregs expanded but, based on their transcriptome profile, became metabolically silent during the treatment	[194]

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