Oncology research has always been one of the important topics in the field of medicine and life sciences. With the continuous development of science and technology, the understanding of tumors is also deepening. Cancer is one of the leading causes of death worldwide, killing millions of people each year. Despite some important progress over the past few decades, there are still significant challenges to cancer prevention and prevention. Therefore, the study of tumorigenesis, progression, and ** has been of great interest.
One of the goals of oncology research is to gain insight into the molecular mechanisms of tumor formation. This includes the origin of the tumor cells, the interaction between the tumor cells and normal cells, and the response of the tumor cells to the method. At the same time, more and more research is focusing on individualization and targeting, with the aim of improving the effectiveness of the product and reducing adverse effects.
Geomx DSP spatial multiomics technology combines tissue image analysis and in situ quantification technology to further realize the in-situ detection and analysis of the whole transcriptome (20,000 genes) and proteome (570 proteins) expression in regions of interest (ROI) at different locations on the basis of showing the global tissue morphological structure, which is convenient for in-depth analysis of tumor microenvironment heterogeneity in tumorigenesis and development.
Cholangiocarcinoma
molecular portraits of patients with intrahepatic cholangiocarcinoma who diverge as rapid progressors or long survivors on chemotherapy
doi:10.1136/gutjnl-2023-330748.
if：
journal：gut
panel：geomx dsp + ncounter | rna (human) -immune pathways panel
Summary:Cytotoxic agents are the cornerstone of patients with advanced intrahepatic cholangiocarcinoma (ICCA), although the benefits vary. We hypothesize that the pretreatment molecular profile of a diagnostic biopsy can ** the patient's benefit from chemotherapy and determine the molecular basis of congenital chemotherapy resistance. We found a cohort of patients with advanced ICCA with similar baseline characteristics who showed extreme outliers during the course of chemotherapy**. Diagnostic biopsies are identified by digital pathology, followed by whole-transcriptome analysis of large tissue regions and geospatial large slice tissue regions. Spatial transcriptomic studies of tumor-infiltrating myeloid cells by GEOMX. Here, we evaluated the transcriptomic characteristics of multiple groups of excised cancers, as well as the analysis of features using in vitro cell lines, in vivo mouse models, and single-cell RNA sequence data. The results suggest that RPLS characteristics may be a novel measure of ICCA chemotherapy outcomes. Further development and validation of this transcriptomic signature is necessary in order to develop precision chemotherapy strategies in these situations.
Twelve cases of cholangiocarcinoma biopsies were analyzed on a nanostring geomx digital analyzer.
Lung cancer
upregulation of indoleamine 2,3-dioxygenase 1 in tumor cells and tertiary lymphoid structures is a hallmark of inflamed non-small cell lung cancer
doi:10.1158/1078-0432.ccr-23-1928.
if：
panel：geomx dsp + ngs | wta (human)
Summary:The tryptophan lysing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed in several tumor types, including non-small cell lung cancer (NSCLC), and has been shown to promote tumor immune evasion and inhibit T cell activation by increasing tryptophan degradation and the production of several immunosuppressive metabolites collectively known as kynurenine. However, it remains unclear whether the expression of IDO1 by tumor cells is harmful in the presence of PD-1 PD-L1 blockage. We analysed the transcriptomes of 891 NSCLC tumor samples from patients enrolled in two large randomized clinical trials to investigate the safety and activity of atezolizumab, a humanized IgG1 mAb targeting PD-L1, versus docetaxel in patients with advanced NSCLC. We complemented these transcriptomic results at the protein level by using multiplex immunofluorescence techniques and at the functional level by in vitro experiments. The study found that the IDO1 pathway in NSCLC is driven by the immune system rather than tumor cells. The combination of IDO1 with anti-PD-1 PD-L1 may be beneficial only in patients with inflammatory tumors, particularly those with TLS.
Tumor sections from six patients were analyzed using a whole transcription** panel on the NanoString Geomx platform.
Esophageal cancer
multi‐omics analyses reveal spatial heterogeneity in primary and metastatic oesophageal squamous cell carcinoma
doi:10.1002/ctm2.1493.
if：
panel：geomx dsp + ncounter | protein (human) -human immune cell profiling panel
Summary:Biopsy of primary esophageal squamous cell carcinoma (ESCC) can guide the diagnosis and**. However, intratumoral spatial heterogeneity can affect the information obtained from biopsy and the response. Here, we aim to elucidate the spatial intratumoral heterogeneity of ESCC and matched lymph node metastases (LNMETs). Here, whole-exome sequencing, whole-transcriptome sequencing, and DSP were used to evaluate the superficial (PTSUP), deep (PTDEEP), and LNMETS subregions of primary tumors in patients with locally advanced resectable ESCC. To validate the results, immunohistochemistry and single-cell transcriptome dataset analysis were also performed. This study comprehensively characterizes spatial heterogeneity in ESCC, and the findings highlight the clinical significance of unbiased molecular classification based on multi-omics data and its potential to improve the understanding and management of ESCC.
DSP analysis was performed from specimens collected at the time of resection in 21 patients (PTSUP, PTDEEP, and matched LNMETs). The panel of choice is a panel of human immune cell atlases, including immune checkpoints, proteins that label different immune cell types (T cells, B cells, macrophages, DC, and NK cells), and other immunomodulatory proteins.
Brain cancer
glioblastoma pseudoprogression and true progression reveal spatially variable transcriptional differences
doi:10.1186/s40478-023-01587-w
if:
panel：geomx dsp + ngs; ncounter | wta (human); ncounter - pan-cancer 360 panel
Summary:During follow-up of patients with glioblastoma, radiographic monitoring after resection to identify areas of new or progressive enhancement is critical. However, pseudoprogressions associated with ** have similar imaging features but require different clinical progressions. Although pathologic diagnosis is the gold standard for distinguishing between true and pseudoprogression, it is due to the lack of objective clinical criteria and confounding histologic findings. We demonstrated that the level of cancer immune cell activity correlated with heterogeneous clinical outcomes in patients using the RNAseq library of glioblastoma samples. In addition, RNA expression analysis of 48 clinical samples resected by the second neurosurgical procedure showed that the pseudoprogression gene expression pathway was dominated by immune activation, while the progression was dominated by cell cycle activity. Spatially derived data further highlight the polarization of myeloid cell populations, which may emphasize the tumor-origin nature of the new lesion. These findings not only help to further clarify the potential targets of pathologists and better aid in stratification of advanced and pseudo-progressive phases, but also highlight the evolution of changes in the tumor immune microenvironment that promote tumors**.
The study used fluorescent staining for region of interest (ROIS) selection and covered the digital pathology IHC for H&E, CD163, OLIG2, Ki67, and P53, selecting regions of interest according to the following histological definitions: normal histology [predominance of normal neuronal histology at H&E], normal surveillance microglia for CD163, normal post-axonal oligodendrocyte growth for OLIG2]; ultracellular histology [predominantly abnormal cellular structures with evidence of active proliferation of OLIG2, Ki67, and p53]; Histology of inflammation [predominantly CD163 leads to increased macrophage microglial infiltration].
Pancreatic cancer
molecular analysis of xpo1 inhibitor and gemcitabine–nab‐paclitaxel combination in kpc pancreatic cancer mouse model
doi:10.1002/ctm2.1513
if：
journal：clin transl med.
panel：geomx dsp + ngs | wta (mouse); protein (mouse) -pan‐tumour panel
Summary: Most patients with pancreatic ductal adenocarcinoma (PDAC) experience disease progression while receiving gemcitabine and nanoparticle albumin-bound paclitaxel (GEMPAC)**, so this disease requires a more effective** strategy. Previously, we have demonstrated that XPO1 is a potent ** target for pancreatic cancer, and Selinexor, a selective inhibitor of nuclear export, can synergistically enhance the efficacy of GEMPAC in pancreatic cancer and has good activity in phase I studies. Here, we utilized DSP and monoRNA sequencing to investigate the pairing of the SEL-GEMPAC combination with LSL-KRASG12D+; lsl-trp53r172h/+;Effects of a mouse model of PDX1-Cre (KPC). The results show that SEL-GEMPAC** interferes with PDAC-supporting signaling networks in a mouse model of KPC.
to control group and treated LSL-KRASG12D+; lsl-trp53r172h/+;PDX1-Cre (KPC) mouse tumors were analyzed for DSP.
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