Single-cell analysis of tumors: Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells

Table 1 Single-cell sequencing studies on variety of human tumors

Tumor type	Source	Platform	Major finding	Ref.
Bladder cancer	Squamous cell carcinoma	RNA-seq	Cellular heterogeneity in the gene expression affects the disease outcome	[73]
	Muscle-invasive cell carcinoma	SNV-seq	Lineage-specific mutations are driving cancer initiation and progress	[74]
Blood cancer	B-cell ALL	CNV-seq	CNVs were developed as an impact of environmental stressors, which was only detectable at single-cell level	[75]
	Pediatric ALL	SNV-seq	Analysis revealed clonal somatic mutational prevalence at single-cell resolution	[76]
	Therapy resistant AML	RNA-seq	Identified molecular signature of resistant LSCs versus therapy-naive LSCs	[77]
	Secondary AML	SNV-seq	Genomic complexity was identified at single cells which was not seen at bulk leukemic populations	[78]
	CML	RNA-seq	Single-cell analysis uncovered molecular signature of LSCs	[57]
	JAK2 negative MPN	SNV-seq	Large genetic distances was observed between mono-clonal tumor cells	[79]
	JAK2V617F MPN	RNA-seq	Single-cell sequencing revealed the molecular networks driving self-renewal of CSCs	[80]
Brain cancer	EGFR amplified GBM	CNV-seq	Heterogeneity in EGFR mutations among different tumor cells leading to variation in therapy response	[81]
	GBM	RNA-seq	Heterogeneity in gene expression panthers was identified including EGFR gene	[82]
Breast cancer	ER+	CNV-seq	Showed clonal evolution of tumor cells at single-cell resolution	[83]
	HER2+	RNA-seq	404 differentially expressed gene signature was identified in CSCs, which had a prognostic value	[84]
	MDA-MB-231 and CN34 cell lines	RNA-seq	Gene expression profiling identifies small sub-population with more metastatic potential, which was therapy resistant.	[85]
	TNBC	CNV-seq	Showed clonal evolution of tumor cells at single-cell level. Also, chemo-resistance evolution in TNBC was identified	[86,87]
		RNA-seq
	TNBC or ER+ HER2-	SNV-seq CNV-seq	ER+ HER2- tumors represented significantly less mutational rate compared to TNBC tumors	[88]
Colorectal cancer	Colon tumor and adjacent normal cells	SNV-seq	Different mutational profiles were identified among tumors’ sub-populations	[89]
	Colon tumor	CNV-seq	CSCs (EpCAMhighCD44+) and DTCs (EpCAMhighCD44-) had similar somatic CNV pattern, while they had regional differences	[90]
	Rectal tumor	CNV-seq	Multi-region single-cell analysis showed somatic copy number alterations are an early event in cancer development	[91]
Kidney cancer	ccRCC primary carcinoma and paired metastasis	RNA-seq	Heterogeneity in the expression of targetable genes was identified. The finding highlights the necessity of multi-agent therapies	[92]
Lung cancer	NSCLC	RNA-seq	Characterization of tumor-infiltrating T cells revealed that inter-tissue effector T cells with a highly migratory nature	[93]
	Clear cell renal cell carcinoma	SNV-seq	A complex mutational pattern was observed at single-cells compared to bulk tumors	[94]
	Adenocarcinoma PDX	RNA-seq	Single-cell sequencing identified KRAS+ drug resistant cell population within the tumor	[95]
	LC2/ad and LC2/ad-R cell lines	RNA-seq	Gene expression profiling identifies signature that is linked to therapy resistance	[96]
Ovarian cancer	HGSOC	RNA-seq	Single-cell analysis could distinguish two major sub-populations within the tumor based on their gene expression signature	[56]

ALL: Acute lymphoblastic leukemia; AML: Acute myeloid leukemia; ccRCC: Clear cell renal cell carcinoma; CML: Chronic myeloid leukemia; CNV: Copy number variant; CSC: Cancer stem cell; DTC: Differentiated tumor cell; HER2: Human epidermal growth factor receptor 2; ER: Estrogen receptor; EGFR: Epidermal growth factor receptor; GBM: Glioblastoma; HGSOC: High grade serous ovarian carcinomas; JAK2: Janus kinase 2; KRAS: Kirsten rat sarcoma viral oncogene homolog; LSC: Leukemia stem cell; MPN: Myeloproliferative neoplasm; NSCLC: Non-small-cell lung carcinoma; PDX: Patient-derived xenograft; SNV: Single nucleotide variant; TNBC: Triple negative breast cancer.