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Boxplot showing relative PHGR1 mRNA levels in primary colon tumors, normal lymph nodes (LNs), and HES-positive (HES+) and-negative (HES−) SLNs. The horizontal line shows the threshold used to characterize the SLNs as positive or negative for the marker.
Source publication
Background:
Regional lymph node (LN) metastasis is a strong and well-established prognostic factor in colon cancer, and recent data suggest a prognostic value of detecting micrometastases and isolated tumor cells in regional LNs. The aim of the study was to investigate the clinical relevance of detecting sentinel lymph node (SLN) metastases in col...
Contexts in source publication
Context 1
... LNs from patients with benign colon disease were used as a reference group. Figure 2 shows the results in comparison to previously reported levels of PHGR1 mRNA in primary tumors from the same patients [14]. Compared to normal LNs, the PHGR1 mRNA levels were significantly higher in both HES-positive and HES-negative SLNs (Pb.001 for both). ...
Context 2
... stratification of pN0 patients by MSI status did not reveal any significant prognostic differences among the resulting subgroups (results not shown). PHGR1 mRNA levels were downregulated in a subset of primary tumors (Figure 2), possibly reducing its potential for the detection of neoplastic cells from these tumors [25]. Interestingly, there was a tendency towards lower primary tumor PHGR1 mRNA levels in the seven patients with SLNs negative for PHGR1 mRNA despite known nodal disease. ...
Context 3
... LNs from patients with benign colon disease were used as a reference group. Figure 2 shows the results in comparison to previously reported levels of PHGR1 mRNA in primary tumors from the same patients [14]. Compared to normal LNs, the PHGR1 mRNA levels were significantly higher in both HES-positive and HES-negative SLNs (Pb.001 for both). ...
Context 4
... stratification of pN0 patients by MSI status did not reveal any significant prognostic differences among the resulting subgroups (results not shown). PHGR1 mRNA levels were downregulated in a subset of primary tumors (Figure 2), possibly reducing its potential for the detection of neoplastic cells from these tumors [25]. Interestingly, there was a tendency towards lower primary tumor PHGR1 mRNA levels in the seven patients with SLNs negative for PHGR1 mRNA despite known nodal disease. ...
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Citations
... 42 For lymphatic cells, upregulation of PHGR1 and TFF3 was observed, which is essential for the invasion and metastasis of colorectal cancer. 43,44 Notably, high expression of NOTCH4 and HSPG2 in tip cells were associated with poor prognosis of MCA patients ( Figure 6G). Additionally, expression information of EndMT-related genes, including transcription factors (TWIST1 and ZEB1), mesenchymal biomarker genes (CD44, S100A4, COL1A1, and COL1A2), and vascular endothelial growth factors (VEGFA, VEGFB, and VEGFC), was detected for the three subtypes. ...
Background
Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in‐depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies.
Methods
We integrated single‐cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three‐dimensional bioprinting technique, canonical ex vivo co‐culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME.
Results
This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7⁺/THBS1⁺ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte‐mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A⁺ macrophages that exhibit M2‐phenotype were enriched in the tumoral niche and high expression of MS4A4A⁺ was associated with poor prognosis in the cohort data. The ligand‐receptor‐based intercellular communication analysis revealed the tight interaction of MUC1⁺ malignant cells and ZEB1⁺ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications.
Conclusions
Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA.
Key points
Tumour microenvironment profiling of MCA is developed.
MUC1⁺ tumour cells interplay with FGF7⁺/THBS1⁺ myofibroblasts to promote MCA development.
MS4A4A⁺ macrophages exhibit M2 phenotype in MCA.
ZEB1⁺ endotheliocytes engage in EndMT process in MCA.
... It was also effective in the evaluation of patients with CRC undergoing immunotherapy. Examination of the 10-gene signature molecular model's gene functions in existing literature indicated that high expression of SLC2A3 [29], MMP11 [30], SCARA3 [31], GPC1 [32], OLFM2 [33], L1CAM [34], CRABP2 [35] is linked to adverse cancer progression, and elevated expression of PHGR1 [36], TFF1 [37], and CLCA1 [38] is associated with a good prognosis of tumors. ...
Colorectal cancer represents a significant health threat, yet a standardized method for early clinical assessment and prognosis remains elusive. This study sought to address this gap by using the Seurat package to analyze a single-cell sequencing dataset (GSE178318) of colorectal cancer, thereby identifying distinctive marker genes characterizing various cell subpopulations. Through CIBERSORT analysis of colorectal cancer data within The Cancer Genome Atlas (TCGA) database, significant differences existed in both cell subpopulations and prognostic values. Employing WGCNA, we pinpointed modules exhibiting strong correlations with these subpopulations, subsequently utilizing the survival package coxph to isolate genes within these modules. Further stratification of TCGA dataset based on these selected genes brought to light notable variations between subtypes. The prognostic relevance of these differentially expressed genes was rigorously assessed through survival analysis, with LASSO regression employed for modeling prognostic factors. Our resulting model, anchored by a 10-gene signature originating from these differentially expressed genes and LASSO regression, proved adept at accurately predicting clinical prognoses, even when tested against external datasets. Specifically, natural killer cells from the C7 subpopulation were found to bear significant associations with colorectal cancer survival and prognosis, as observed within the TCGA database. These findings underscore the promise of an integrated 10-gene signature prognostic risk assessment model, harmonizing single-cell sequencing insights with TCGA data, for effectively estimating the risk associated with colorectal cancer.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12672-023-00789-x.
The concept of sentinel node (SN) is an important aspect of surgical oncology that has revolutionized the treatment of solid tumors. The concept of sentinel node mapping suggests that lymphatic basin involvement starts from the sentinel nodes, and if sentinel nodes are pathologically clear from tumor cells, the other lymph nodes of the basin are clear either. In the current chapter, general aspects of sentinel node mapping have been discussed, including various mapping materials and radiopharmaceuticals; injection site, time, dose, and volume; imaging (lymphoscintigraphy); and gamma-probe-related issues. Special considerations for sentinel node mapping in breast cancer, melanoma, and uterine cervix, endometrial, vulvar, penile, colorectal, and head and neck cancers were also discussed.
