Introduction to Tumor Cluster

What is/are Tumor Cluster?

Tumor Cluster - Purpose To determine the potential findings associated with vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma (HCC), with particular emphasis on texture analysis based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. ^[1] • Radiomics models are useful for predicting vessels encapsulating tumor clusters (VETC) and patient prognosis preoperatively. ^[2] However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. ^[3] The term ‘‘vessels that encapsulate tumor cluster (VETC)’’ was first proposed in 2015 by Fang et al. ^[4] In IDH-wildtype glioblastomas (n = 2,072), we identified distinct tumor clusters based on immune cell proportion and demonstrated an association with oncogenic alterations such as EGFR amplification and CDKN2A/B homozygous deletion. ^[5] Vessels that encapsulate tumor clusters (VETC) is a novel described vascular pattern different from microvascular invasion (MVI) for patients with hepatocellular carcinoma (HCC). ^[6] Unsupervised hallmark pathway clustering demonstrated an immune-related tumor cluster containing the immune content score. ^[7] OBJECTIVES To investigate the noninvasive prediction of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) based on qualitative and quantitative imaging features of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. ^[8] Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology tumor clusters associated with immune signaling, development, and cellular signaling pathways. ^[9] Our tumor clusters were related to grade, survival status. ^[10] Results: Novel markers for the prediction of satellite nodules and a tumor clusters specific marker genes signature model(6 genes) for HCC prognosis was constructed, respectively. ^[11] Understanding integrated mechanosensing features within tumor cluster and smooth muscle and potential triggers within adjacent adipose tissue, such as the unique damage-associated molecular pattern protein (DAMP), eNAMPT (extracellular nicotinamide phosphoribosyltransferase), or visfatin, offers an opportunity to prevent the first steps of invasion and metastasis through the structured muscle. ^[12] Stratification based on SUVmax, PD‐L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. ^[13] There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). ^[14] High tumor budding was also associated with poor prognostic histological features, including poorly differentiated tumor clusters and infiltrative tumor borders. ^[15] Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. ^[16] Additionally, endothelial‐like cells were observed at the periphery of the tumor clusters; fibrin was evident in the clusters. ^[17] Results Glycolytic expression distinguished a tumor cluster enriched for wild-type IDH and poorer overall survival (P <. ^[18] Tumor clustering was determined by averaging local clustering of regions overlapping with the tumor, and vice versa for non-tumor regions. ^[19] Objective: To investigate the molecular mechanism of nest metastasis in blood vessels encapsulated by tumor clusters (VETC) positive hepatocellular carcinoma (HCC). ^[20] RESULTS Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumor clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, p<0. ^[21] While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters. ^[22] We demonstrated that both EB and IB induced closer cell-cell contacts within the tumor cluster, but cancer cell viability was reduced only in the presence of IB. ^[23] Background Macrotrabecular-massive (MTM) subtype and vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. ^[24] Methods The degree of tumor clustering segmented from T1 weighted images is measured to every other tumor by a function of lesion similarity to each other via the Hausdorff distance. ^[25] The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early‐stage hepatocellular carcinoma (HCC) remains unclear. ^[26] Wheat germ agglutinin staining clearly identified tumor clusters within the surrounding stroma, and tumor cells with elongated morphology. ^[27] We have shown that VETC (vessels encapsulating tumor clusters) mediates invasion-independent metastasis, whereas VETC- HCCs metastasize in an invasion-dependent manner. ^[28] Conclusions Analysis of cytokines in the aqueous humor shows distinct differences between aqueous humor samples and allocates these samples into three different prognostic tumor clusters. ^[29] Emerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. ^[30] The predictive value of TILs assessed using the ITWG system was superior to the assessment of intraepithelial lymphocyte performed prospectively using a standard system requiring ≥5 lymphocytes per high-powered field in direct contact with tumor cells or between tumor clusters. ^[31] As a result, we found 4 tumor clusters that overcome the heterogeneity in mutation profiles, and reveal predominant pathways in each group. ^[32] Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells in vivo. ^[33] We demonstrate a new diagnostic method, the Photodynamic Infrared Spectroscoppy (PDIS), which is able to detect circulating tumor clusters and circulating tumor cells in the circulatory system. ^[34] Targeting smaller populations of circulating tumor clusters (CTC) with tumor-initiating and colonization potentials at distant sites in circulation remains a challenge as clusters possess both epithelial and mesenchymal characteristics. ^[35] According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. ^[36] Tumor budding is defined as the presence of single tumor cells or small tumor clusters (less than five cells) that ‘bud’ from the invasive front of the main tumor. ^[37] In this paper, we introduce manifold regularization into low-rank representation model and present a novel method named Mixed-norm Laplacian regularized Low-Rank Representation (MLLRR) to identify the differentially expressed genes for tumor clustering based on gene expression data. ^[38] In earlier research works, various tumor clustering schemes were presented based on the single clustering systems and implemented successfully to a variety of biomolecular data for cancer class detection. ^[39] Using a seed point the center of the tumor cluster is defined. ^[40] The successful differentiation of tumor cell clusters from non-tumor clusters provides the basis for the identification of tumor clusters in hydrothorax. ^[41] Various morphological patterns of metastasis were assessed in 440 positive LNs and then classified into 4 groups: common type, direct type (continuously invaded by the main tumor), scatter type (multiple tumor clusters among the normal LN tissues), and isolated tumor cell (ITC). ^[42] We analyzed the two main clusters of patients with clinical parameters, and found that the tumor clusters were statistically and significantly associated with primary tumor stage (P  Conclusions The radiomic features from medical images could be helpful in deciphering T-stages, metastasis and benign of RCC and may have potential as imaging biomarker for prediction of RCC overall survival. ^[43] We investigated the clinical significance of a vascular growth pattern of hepatocellular carcinoma (HCC), the vessels that encapsulate tumor clusters (VETC), previously linked to HCC metastatic dissemination. ^[44] Our work provides evidence that CD8+ T cells can cross typical fibrotic barriers and thus their infiltration into tumor clusters is governed by other mechanisms possibly involving a local repellent. ^[45] Geometrical anisotropy, supramolecular nanoarchitecture, and multiplex functionalities exemplified by various techniques incites the development of integrated multi–modal drug delivery systems for circulating tumor clusters (CTC). ^[46] Tumor clusters >0. ^[47] The increased metastatic capability of small circulating tumor clusters/spheroids may be explained by their role as putative precursors of tumorospheres eventually trapped in capillaries. ^[48] RESULTS Unsupervised hierarchical clustering of hallmark pathways demonstrated an immune-related tumor cluster. ^[49] CD44 homophilic interactions and subsequent CD44-PAK2 interactions mediate tumor cluster aggregation. ^[50]

Encapsulating Tumor Cluster

Purpose To determine the potential findings associated with vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma (HCC), with particular emphasis on texture analysis based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. ^[1] • Radiomics models are useful for predicting vessels encapsulating tumor clusters (VETC) and patient prognosis preoperatively. ^[2] OBJECTIVES To investigate the noninvasive prediction of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) based on qualitative and quantitative imaging features of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. ^[3] Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. ^[4] RESULTS Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumor clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, p<0. ^[5] Background Macrotrabecular-massive (MTM) subtype and vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. ^[6] The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early‐stage hepatocellular carcinoma (HCC) remains unclear. ^[7] We have shown that VETC (vessels encapsulating tumor clusters) mediates invasion-independent metastasis, whereas VETC- HCCs metastasize in an invasion-dependent manner. ^[8]

Encapsulate Tumor Cluster

The term ‘‘vessels that encapsulate tumor cluster (VETC)’’ was first proposed in 2015 by Fang et al. ^[1] Vessels that encapsulate tumor clusters (VETC) is a novel described vascular pattern different from microvascular invasion (MVI) for patients with hepatocellular carcinoma (HCC). ^[2] Stratification based on SUVmax, PD‐L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. ^[3] There is limited published information about prognostic value of vessels that encapsulate tumor cluster (VETC) based on their involvement with immune cells in hepatocellular carcinoma (HCC). ^[4] We investigated the clinical significance of a vascular growth pattern of hepatocellular carcinoma (HCC), the vessels that encapsulate tumor clusters (VETC), previously linked to HCC metastatic dissemination. ^[5]

Circulating Tumor Cluster

We demonstrate a new diagnostic method, the Photodynamic Infrared Spectroscoppy (PDIS), which is able to detect circulating tumor clusters and circulating tumor cells in the circulatory system. ^[1] Targeting smaller populations of circulating tumor clusters (CTC) with tumor-initiating and colonization potentials at distant sites in circulation remains a challenge as clusters possess both epithelial and mesenchymal characteristics. ^[2] Geometrical anisotropy, supramolecular nanoarchitecture, and multiplex functionalities exemplified by various techniques incites the development of integrated multi–modal drug delivery systems for circulating tumor clusters (CTC). ^[3] The increased metastatic capability of small circulating tumor clusters/spheroids may be explained by their role as putative precursors of tumorospheres eventually trapped in capillaries. ^[4]

Related Tumor Cluster

Unsupervised hallmark pathway clustering demonstrated an immune-related tumor cluster containing the immune content score. ^[1] RESULTS Unsupervised hierarchical clustering of hallmark pathways demonstrated an immune-related tumor cluster. ^[2]