Table 3.
The application of scRNA-seq in tumor resistance
| Tumor | Application of scRNA-seq | Research achievement | Reference | |
|---|---|---|---|---|
| Triple-negative breast cancer | scRNA-seq and exome sequencing were used to analyze longitudinal samples of 20 TNBC patients undergoing neoadjuvant chemotherapy | the chemotherapy-resistant genotype of TNBC is preexisting and adaptively selected by NAC, while the transcription profile of TNBC patients after chemotherapy is obtained by reprogramming | 69 | |
| Triple-negative breast cancer | scRNA-seq was performed on >1,500 cells of six major TNBCs | different malignant cell subsets shared by multiple tumors were identified, including a subgroup associated with multiple therapeutic drug resistance, characterized by the activation of glucose and lipid metabolism and related innate immune pathways | 70 | |
| Breast cancers | the contribution of genetic diversity and transcriptional plasticity in early and late endocrine therapy (ET) at single-cell resolution was analyzed | a rare pre-adapted (PA) cell subset undergoes further transcriptional recombination and copy number changes to achieve complete resistance; a multi-stage development model of ET resistance was proposed | 71 | |
| Breast cancer | scRNA-seq, cell barcoding, and mathematical modeling have been used to study endocrine resistance in breast cancer | endocrine resistance is due to the selection of cells with existing genetic differences, while the resistance of KDM5 inhibitors is acquired; phenotypic heterogeneity is associated with drug resistance, and KDM5A/B is a key regulator of this process | 72 | |
| Breast cancer | cells were enriched with different degrees of CSC properties in breast cancer cell line MDA-MB-231, and scRNA-seq was performed | fourteen significantly upregulated genes were found in the CSC population, which is very important for the study of metastasis and treatment of drug resistance | 40 | |
| Breast cancer | scRNA-seq was used to map the entire ER+ breast cancer microenvironment | a new subgroup of CD63+ carcinoma-associated fibroblasts (CAFs) is revealed to induce breast cancer resistance to tamoxifen through exosome Mir-22, suggesting that CD63+ CAFs may be a new therapeutic target for improving tamoxifen sensitivity | 73 | |
| Breast cancer | scRNA-seq analysis was used on samples from patients with progressive ER+ metastatic breast cancer | histone deacetylase (HDAC) inhibition can block chemotherapy-induced drug resistance phenotypes in refractory breast cancer cells through a “one-two punch” strategy | 74 | |
| Breast cancer | scRNA-seq of CTCs isolated from blood samples of patients with metastatic ER+ breast cancer was performed to compare the progression of bone and internal organs | the expression of AR in tumor cells was related to the treatment time of aromatase inhibitors, suggesting that it was related to resistance to acquired endocrine therapy | 23 | |
| Breast cancer | the large-volume scRNA-seq technique was used to track the evolution of genetic and phenotypic subclones of four kinds of breast cancer in order to better understand how breast cancer develops drug resistance | after treatment, the tumor acquired a malignant phenotype, including enhanced matrix and growth factor signals, which may promote drug resistance | 75 | |
| Breast cancer | scRNA-seq was used in breast cancer | the results underscore the need to consider lineage-specific tumor-propagating cells (TPCs) and grade composition of breast tumors, as these heterogeneous subsets may have different treatment sensitivities | 76 | |
| Breast cancer | scRNA-seq was performed on invasive ductal breast carcinoma (IDC) and invasive lobular breast carcinoma (ILC) cell lines and a group of CRISPR-Cas9-mediated E-cadherin gene knockout IDC cell lines (T47D) | remodeling of the transcriptional membrane system is similar to that of ILCs in the activation of regulatory factors, and it increases the sensitivity to interferon (IFN)-H-mediated growth inhibition by activating IRF1 | 77 | |
| Melanoma | scRNA-seq and computational analysis were used to study the status of malignant cells promoting immune evasion in 33 melanoma tumors | CDK4/6 inhibition combined with immunotherapy reduces melanoma tumor growth, and the study provides a high-resolution picture of immune checkpoint inhibitor (ICI)-resistant cell status | 78 | |
| Lung adenocarcinoma | scRNA-seq data of patients with lung adenocarcinoma were analyzed to characterize the heterogeneity of genes related to immune response in the tumor | downregulation of the IFN-H signal pathway gene corresponds to the phenotype of acquired drug resistance | 79 | |
| High-grade serous ovarian cancer | about 11,000 cells from 11 ascites patients with high-grade serous ovarian cancer (HGSOC) were analyzed by scRNA-seq | inhibition of the expression of the JAK/STAT pathway in malignant cells and tumor-associated fibroblasts showed strong anti-tumor activity, which further clarified the mechanism of drug resistance in patients with ascites | 80 | |
| Muscle-invasive urothelial bladder cancer | scRNA-seq was used to describe the tumor landscape of a case of chemotherapy-resistant metastatic muscle-invasive urothelial bladder cancer (MIUBC) | clinical application of the PD-L1 inhibitor atezolizumab resulted in a good acquired response to patients resistant to tipifarnib | 81 | |
| Prostate cancer | scRNA-seq was performed on docetaxel-sensitive and drug-resistant variants of DU145 and PC3 prostate cancer cell lines | NUPR1 was identified as a mediator of drug resistance in prostate cancer, providing a theoretical basis for exploring the reversal of docetaxel resistance of NUPR1 and its target genes | 82 | |
| Glioblastoma multiforme | scRNA-seq was used on GBM | GBM shows four subtypes, among which proneural and mesenchymal are the main types, with the latter showing stronger invasive and treatment resistance | 83 | |
| Glioma | combining scRNA-seq data with clinical bulk gene expression data, a computational pipeline was developed for identifying prognostic and predictive characteristics linking cancer cells to microenvironmental cells; the pipeline was applied to glioma scRNA-seq data | multilayer network biomarker (MNB) can predict the sensitivity or drug resistance of glioma patients to molecular targeted therapy | 84 | |
| Chronic myeloid leukemia | high-sensitivity mutation detection combined with the same single-cell full transcriptometric analysis was used to analyze more than 2,000 stem cells from patients with CML throughout the course of the disease | a CML-SCs subgroup with distinct molecular characteristics was identified, which persisted selectively during long-term treatment and was related to drug resistance | 53 | |
| Acute lymphoblastic leukemia | scRNA-seq and several complementary genomic maps were used to compare the differentiation of normal B lines and the status of leukemic cells in vivo | abundance of the G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during the induction of chemotherapy represent features of chemoresistance | 85 | |
| Acute lymphoblastic leukemia | full-length scRNA-seq was performed on malignant and microenvironmental cells | lineage plasticity and stemness have been used as the cause of cancer treatment resistance, the mechanism of which is the activation of NOTCH1 mutations in recurrent/refractory early T cell progenitor cells | 86 | |
| Acute lymphoblastic leukemia | scRNA-seq data and several complementary genomic maps were used to compare normal B-line differentiation and leukemic cell status in vivo | the G1 cell cycle state is abundant, and there is a lack of differentiation-related regulatory network changes during induced chemotherapy, which is a characteristic of chemotherapeutic resistance | 87 | |
| Melanoma | the published scRNA-seq dataset was analyzed from melanoma patients treated with immune checkpoint therapy (ICT) | identified and validated a feature of immune cells; ImmuneCells.Sig can represent a valuable tool for clinical decision-making in patients receiving immunotherapy | 88 | |
| Tubular renal cell carcinoma | scRNA-seq analysis was performed on 15,208 cells from a pair of primary and metastatic sites that collected tubular renal cell carcinoma | effective inhibitors of PARP, PIGF, HDAC2, and FGFR targeting CSCs may be potential therapeutic strategies for CDRCC | 58 | |
| Basal cell carcinoma | three prognostic surface markers (LYPD3, TACSTD2, and LY6D) associated with drug resistance to nuclear myocardin-related transcription factor (nMRTF) and Smoothened (SMO) inhibitors were identified using scRNA-seq from the patient’s tumor | basal cell carcinoma (BCC) is dependent on hedgehog (Hh)/Gli signaling pathways, but can form SMO inhibitor resistance mechanisms, with AP-1 and TGF reagent groups synergistically driving the activation of nMRTF; the JNK/AP-1 signal promotes nMRTF activity through chromatin accessibility and Smad3 DNA binding, leading to Rho guanine exchange factor (RhoGEF) transcription; small molecule AP-1 inhibitors target human BCC LYPD3+/TACSTD2+/LY6D+ nMRTF in vitro, opening a way for improved combination therapy | 89 | |
| Merkel cell carcinoma | scRNA-seq was used in two patients with metastatic Merkel cell carcinoma (MCC) | dynamic transcriptional suppression of specific HLA genes targeting viral epitopes is present in drug-resistant tumors under intense immune pressure mediated by CD8 | 90 | |
| Merkel cell carcinoma | scRNA-seq was used in the MCC study | domatinostat not only has a direct anti-tumor effect, but it also can restore the surface expression of HLA class I on MCC cells, thus restoring the sensitivity of surviving MCC cells to the recognition and elimination of homologous cytotoxic T cells | 91 | |
| Kidney cancer | a comprehensive immunoassay was performed for established RENCA tumors of renal cell carcinoma by multiparametric flow cytometry, tumor cytokine profile, and scRNA-seq | IL-1B blocking and ICIs or tyrosine kinase inhibitors (TKIs) reshape the intermedullary chamber through a non-redundant and relatively independent T cell mechanism; IL-1B is the upstream mediator of adaptive bone marrow resistance | 92 | |
| Pancreatic ductal adenocarcinoma | scRNA-seq was used to comprehensively study the tumor and tumor microenvironmental content of PDAC tumors in both humans and mice | CAFs are involved in the drug resistance of PDAC; MHC class II can provide antigens to CD4+ T cells, which express CAFs and potentially regulate the immune response of PDAC | 93 | |
| Pancreatic ductal adenocarcinoma | single-cell transcriptology was used to draw an image of fibroblasts during the progression of PDAC in an animal model | the LRRC15CAF pedigree driven by TGF-β is associated with adverse results in immunotherapy trial data containing multiple solid tumors, and it is the target of combined therapy | 94 | |
| – | scRNA-seq analysis was performed on human preimplantation embryos | the awakening of scarce regulatory stemness networks in differentiated cells is related to the development of different spectra of genomic aberrations in many types of clinically fatal malignant tumors, which leads to the emergence of drug-resistant cancer phenotypes | 66 | |
| – | pretreatment tumor biopsy combined with scRNA-seq was used to reveal the underlying mechanisms of avelumab drug resistance | in macrophage cells with extensive immunosuppression, there were pro-inflammatory populations promoting a PD-L1 blocking response | 95 | |
| – | according to scRNA-seq, the tumor microenvironment (TME) was divided into an inflammatory immunotherapy response type and an inflammatory non-response type | the expression of IL-2 signal pathway-related genes in the inflammatory microenvironment is upregulated, while the PPAR signal pathway-related genes and multiple epigenetic pathway-related genes are suppressed and upregulated, respectively, suggesting the possible mechanism of immunotherapy resistance | 96 | |
| – | single-cell transcriptomics were used to study the divergent patterns of chemotherapy resistance in tumor cells | a high degree of intratyphogenic heterogeneity (ITH) facilitates the selection of existing drug-resistant cells, while phenotypic homogeneous cells participate in recessive epigenetic mechanisms for transdifferentiation under drug selection; drug-induced adaptation was achieved after the loss of the stem-factor SOX2 and the acquisition of SOX9, and JQ1-mediated BRD4 inhibition could reverse drug-induced adaptation | 62 | |
| – | bulky and scRNA-seq analysis revealed the inherent characteristics and diversity of unconventional T cell (UTC) antibodies associated with neutrophil-dependent anti-sarcoma immunity | neutrophil-driven UTCs toward zero polarization and type 1 immunity are essential for resistance to murine sarcoma and selective human tumors | 97 | |
| – | the transcriptomic response of cultured colon cancer cell lines to DNA damage induced by 5-fluorouracil (5-FU) was described by scRNA-seq | after 5-FU treatment, a single colon cancer cell population was treated with three different transcriptional phenotypes, which correspond to different cell fate responses: apoptosis, cell cycle checkpoints, and stress resistance | 98 | |
| – | dynamic scRNA-seq was performed on tissue-type tumor globules in mice undergoing PD-1 blockade | a discrete subset of immunotherapy persister cells (IPCs) was identified to be resistant to CD8 T cell-mediated killing; PD-1 blockade and BIRC2/3 antagonism combined to reduce IPCs | 64 | |
| – | single-cell transcriptome data of human melanoma and non-small cell lung cancer (NSCLC) specimens were analyzed | TOX promotes the depletion of CD8 T cells in tumor by upregulating IC molecules, suggesting that TOX inhibition may hinder T cell depletion and improve the efficacy of ICIs | 99 | |