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Table 3 Key findings related to malignant cell heterogeneity among tumors obtained using single-cell sequencing

From: Applications of single-cell sequencing in cancer research: progress and perspectives

Tumor

Technology

Platform

Key findings

References

PDAC

scRNA-seq, trajectory analysis

10X Genomics

Identified 11 subpopulations of malignant tumor cells, including a subset of malignant ductal cells with unique proliferative features associated with the inactivation of tumor-infiltrating T cells

[90]

PDAC

scRNA-seq, trajectory analysis

10X Genomics

Identified 6 acinar metaplastic cell subpopulations during the progression from preinvasive stages to tumor formation in a mouse model

[212]

LUAD, LUSC

Bulk and scRNA-seq

10X Genomics

Revealed that nongenetic heterogeneity is a major predictor of phenotypic heterogeneity

[78]

LUAD

scRNA-seq

10X Genomics

Identified 19 tumor-specific markers as candidate markers for the detection of extraordinarily rare circulating tumor cells

[213]

lung cancer

Single-cell sequencing

CyTOF

Revealed that AXL inhibition suppresses SMAD4/TGFβ signaling and induces JAK1/STAT3 signaling pathways, and AXL functions via CD133-mediated cancer stemness and hybrid EMT features in patients with advanced-stage tumors

[214]

GGN-ADC, SADC

scRNA-seq, flow cytometry

10X Genomics

Revealed the downregulation of signaling pathways associated with angiogenesis and cell proliferation, low expression of collagens of fibroblasts and activated immune cells in GGN-ADC

[215]

melanoma

scRNA-seq, bulk RNA-seq, ATAC-seq

10X Genomics

Confirmed the intermediate state of melanoma cells, which is governed by SOX6, NFATC2, EGR3, ELF1 and ETV4 and regulated by a gene regulatory network

[79]

GA

scRNA-seq

10X Genomics

Identified 5 subtypes of malignant tumor cells, 3 of which corresponded with the histopathological features of Lauren’s subtypes, while 1 was associated with the GA-FG-CCP

[216]

EGC

scRNA-seq

10X Genomics

Revealed that the glandular mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia; HSE6 may help identify early-stage tumors

[216]

AML

scRNA-seq, next-generation sequencing

10X Genomics

Identified 3 leukemia subpopulations arrested at different stages of myeloid differentiation: CD34*CD117dim blasts (blocked in G0/G1 phase), CD34*CD117bri blasts and partial maturation myeloid cells

[217]

MM

scRNA-seq

Fluidigm C1

Identified 4 groups of malignant cells; the L1 group from MGUS expressed the lowest levels of genes involved in oxidative phosphorylation, while the L4 group from MM displayed the highest expression

[218]

NEPC

scRNA-seq

10X Genomics

Revealed that focal neuroendocrine differentiation exclusively originates from luminal-like malignant cells and identified differentiation-association signature genes

[219]

medulloblastoma

scRNA-seq

10X Genomics

Identified OLIG2-expressing glial progenitors as transit-amplifying cells at tumor onset, and they are enriched in therapy-resistant and recurrent medulloblastoma

[220]

glioma

scRNA-seq

10X Genomics

Identified Zfp36l1 as a key gene for glioma growth, various transitional intermediate states and corresponding developmental lineages

[221]

glioblastoma

scRNA-seq

10X Genomics

Identified key genes involved in NSC transformation into tumor-promoting cells; NSCs may promote metastasis via extracellular vesicles

[222]

glioblastoma

scRNA-seq

10X Genomics

Identified RAD51AP1 as an independent prognostic factor and a potent mediator of EGFRvlll signaling

[223]

ESCC

scRNA-seq, bulk sequencing

SMART-Seq 2

Identified genes associated with radioresistance, including autophagy-related 9B, DNA damage-inducible transcript 4, myoglobin and plasminogen activator tissue type

[224]

HCC

scRNA-seq

10X Genomics

Identified the involvement of JUNB, a pro-oncogene, in the immune response and progression of HCC

[225]

HCC

Single-cell mass cytometry, RNA sequencing

Fluidigm

Revealed that the lncRNA HOXA-AS2 is associated with the regulation of cancer stemness during tumorigenesis and poor prognosis; identified an EPCAM + C-MYC + CK19 subpopulation in HOXA-AS2 high patients

[226]

breast cancer

scRNA-seq

Hydro-Seq

Revealed that CAFs increase cancer stemness and alter the epithelial/mesenchymal status during coculture with malignant cells

[111]

breast cancer

Single-cell whole-exome sequencing

Fluidigm C1

Revealed the evolutionary process of cells with SNVs in hit driver genes via CNVs acquired in chromosomal regions; identified the Plekha5 gene as a suppressor of tumor metastasis

[227]

  1. PDAC: pancreatic ductal adenocarcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; GGN-ADC: ground glass nodule adenocarcinoma; SADC: solid adenocarcinoma; GA: gastric adenocarcinoma; GA-FG-CCP: fundic gland-type gastric adenocarcinoma; AML: acute myelogenous leukemia; NEPC: neuroendocrine prostate cancer; EGC: early gastric cancer; ESCC: esophageal squamous cell carcinoma; MM: multiple myeloma; HCC: hepatocellular carcinoma; ESCC: esophageal squamous cell carcinoma