Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma.

Glycine N-acyltransferase (GLYAT), known to influence glycine metabolism, has been implicated in the progression of various malignant tumours. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unexplored. Here, GLYAT expression levels in HCC tissues were significantly reduced compared to normal liver tissues. Similarly, GLYAT expression levels in Huh 7, HepG2, PLC and SK-HEP1 were lower than those in LO2. Receiver operating characteristic curve analysis demonstrated that GLYAT exhibited good diagnostic performance for HCC. Kaplan-Meier analyses suggested that decreased GLYAT expression was correlated with poorer progress in HCC. Low GLYAT expression was significantly associated with gender and histologic grade. Multivariate Cox regression analysis identified low GLYAT expression and T stage as independent prognostic factors. Nomograms based on GLYAT mRNA expression and T stage showed good concordance with actual survival rates at 1, 2, 3 and 5 years. Moreover, GLYAT downregulation in the Huh 7 cell line enhanced cell proliferation, invasion and migration abilities, while GLYAT overexpression in the HepG2 cell line inhibited these abilities. HCC patients with low GLYAT expression exhibited a predisposition to immune escape and poor response to immunotherapy. This research revealed that GLYAT holds promise as both a prognostic biomarker and a potential therapeutic target in HCC.

Single-cell and spatial transcriptomics reveal apelin/APJ pathway's role in microvessel formation and tumour progression in hepatocellular carcinoma.

The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (p = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (p < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes.

Spatial transcriptomics profiling of gallbladder adenocarcinoma: a detailed two-case study of progression from precursor lesions to cancer.

BACKGROUND: Most studies on tumour progression from precursor lesion toward gallbladder adenocarcinoma investigate lesions sampled from distinct patients, providing an overarching view of pathogenic cascades. Whether this reflects the tumourigenic process in individual patients remains insufficiently explored. Genomic and epigenomic studies suggest that a subset of gallbladder cancers originate from biliary intraepithelial neoplasia (BilIN) precursor lesions, whereas others form independently from BilINs. Spatial transcriptomic data supporting these conclusions are missing. Moreover, multiple areas with precursor or adenocarcinoma lesions can be detected within the same pathological sample. Yet, knowledge about intra-patient variability of such lesions is lacking. METHODS: To characterise the spatial transcriptomics of gallbladder cancer tumourigenesis in individual patients, we selected two patients with distinct cancer aetiology and whose samples simultaneously displayed multiple areas of normal epithelium, BilINs and adenocarcinoma. Using GeoMx digital spatial profiling, we characterised the whole transcriptome of a high number of regions of interest (ROIs) per sample in the two patients (24 and 32 ROIs respectively), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Human gallbladder organoids and cell line-derived tumours were used to investigate the tumour-promoting role of genes. RESULTS: Spatial transcriptomics revealed that each type of lesion displayed limited intra-patient transcriptomic variability. Our data further suggest that adenocarcinoma derived from high-grade BilIN in one patient and from low-grade BilIN in the other patient, with co-existing high-grade BilIN evolving via a distinct process in the latter case. The two patients displayed distinct sequences of signalling pathway activation during tumour progression, but Semaphorin 4 A (SEMA4A) expression was repressed in both patients. Using human gallbladder-derived organoids and cell line-derived tumours, we provide evidence that repression of SEMA4A promotes pseudostratification of the epithelium and enhances cell migration and survival. CONCLUSION: Gallbladder adenocarcinoma can develop according to patient-specific processes, and limited intra-patient variability of precursor and cancer lesions was noticed. Our data suggest that repression of SEMA4A can promote tumour progression. They also highlight the need to gain gene expression data in addition to histological information to avoid understimating the risk of low-grade preneoplastic lesions.

Unravelling CD24-Siglec-10 pathway: Cancer immunotherapy from basic science to clinical studies.

Cancer immunotherapy has revolutionized the treatment landscape by harnessing the power of the immune system to combat malignancies. Two of the most promising players in this field are cluster of differentiation 24 (CD24) and sialic acid-binding Ig-like lectin 10 (Siglec-10), and both of them play pivotal roles in modulating immune responses. CD24, a cell surface glycoprotein, emerges as a convincing fundamental signal transducer for therapeutic intervention, given its significant implication in the processes related to tumour progression and immunogenic evasion. Additionally, the immunomodulatory functions of Siglec-10, a prominent member within the Siglec family of immune receptors, have recently become a crucial point of interest, particularly in the context of the tumour microenvironment. Hence, the intricate interplay of both CD24 and Siglec-10 assumes a critical role in fostering tumour growth, facilitating metastasis and also orchestrating immune evasion. Recent studies have found multiple evidences supporting the therapeutic potential of targeting CD24 in cancer treatment. Siglec-10, on the other hand, exhibits immunosuppressive properties that contribute to immune tolerance within the tumour microenvironment. Therefore, we delve into the complex mechanisms through which Siglec-10 modulates immune responses and facilitates immune escape in cancer. Siglec-10 also acts as a viable target for cancer immunotherapy and presents novel avenues for the development of therapeutic interventions. Furthermore, we examine the synergy between CD24 and Siglec-10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec-10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics.

The Structure Characteristics and Function of Non B Cell-Derived Immunoglobulin.

According to classical immunology theory, immunoglobulin (Ig) is exclusively produced by differentiated B lymphocytes, which exhibit a typical tetrapeptide chain structure and are predominantly present on the surface of B cells and in bodily fluids. B-Ig is one of the critical effector molecules for humoral immune responses specifically recognising antigens and eliminating them. However, mounting evidence has demonstrated that Ig is widely expressed in non B lineage cells, especially malignant ones (referred to as non B-Ig). Interestingly, non B-Ig mainly resides in the cytoplasm and secretion, but to some extent on the cell surface. Furthermore non B-Ig not only displays a tetrapeptide chain structure but also shows free heavy chains and free light chains (FLCs). Additionally, Ig derived from non B cancer cell typically displays unique glycosylation modifications. Functionally, non B-Ig demonstrated diversity and versatility, showing antibody activity and cellular biological activity, such as promoting cell proliferation and survival, and it is implicated in cancer progression and some immune-related diseases, such as renal diseases.

The Expression of Non B Cell-Derived Immunoglobulins.

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

GBP1 promotes cutaneous squamous cell carcinoma proliferation and invasion through activation of STAT3 by SP1.

Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC.

Research progress on the structure, function, and use of angiogenin in malignant tumours.

Angiogenin (ANG) is a specialised secreted ribonuclease, also known as RNase5, that is widely expressed in vertebrates. ANG dysregulation is closely associated with the development of breast, nasopharyngeal, and lung cancers. In recent years, studies have found that ANG not only induces neovascularisation by activating endothelial cells, but also plays a regulatory role in the plasticity of cancer cells. Cellular plasticity plays pivotal roles in cancer initiation, progression, migration, therapeutic resistance, and relapse. Therefore, it is a promising biomarker for cancer diagnosis, prognostic evaluation, and therapy. This review summarises the current knowledge regarding the roles and clinical applications of ANG in cancer development and progression.

Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

A review concerning the breast cancer-related tumour microenvironment.

Breast cancer (BC) is currently the most common malignant tumour in women and one of the leading causes of their death around the world. New and increasingly personalised diagnostic and therapeutic tools have been introduced over the last few decades, along with significant advances regarding the study and knowledge related to BC. The tumour microenvironment (TME) refers to the tumour cell-associated cellular and molecular environment which can influence conditions affecting tumour development and progression. The TME is composed of immune cells, stromal cells, extracellular matrix (ECM) and signalling molecules secreted by these different cell types. Ever deeper understanding of TME composition changes during tumour development and progression will enable new and more innovative therapeutic strategies to become developed for targeting tumours during specific stages of its evolution. This review summarises the role of BC-related TME components and their influence on tumour progression and the development of resistance to therapy. In addition, an account on the modifications in BC-related TME components associated with therapy is given, and the completed or ongoing clinical trials related to this topic are presented.

Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress.

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc-deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by a variety of cellular stress. Biologically, STC2 induction and secretion promote cell survival but attenuate cell proliferation during nutrient insufficiency, thus switching the priority of cancer cells from proliferation to survival. Loss of STC2 impairs tumour growth by inducing both apoptosis and necrosis in mouse xenografts. Mechanistically, under nutrient insufficient conditions, cells have increased levels of reactive oxygen species (ROS), and lack of STC2 further elevates ROS levels that lead to increased apoptosis. RNA-Seq analyses reveal STC2 induction suppresses the expression of monoamine oxidase B (MAOB), a mitochondrial membrane enzyme that produces ROS. Moreover, a negative correlation between STC2 and MAOB levels is also identified in human tumour samples. Importantly, the administration of recombinant STC2 to the culture media effectively suppresses MAOB expression as well as apoptosis, suggesting STC2 functions in an autocrine/paracrine manner. Taken together, our findings indicate that nutrient insufficiency induces STC2 expression, which in turn governs the adaptation of cancer cells to nutrient insufficiency through the maintenance of redox homeostasis, highlighting the potential of STC2 as a therapeutic target for cancer treatment.

The multifaceted therapeutic value of targeting steroid receptor coactivator-1 in tumorigenesis.

Steroid receptor coactivator-1 (SRC-1, also known as NCOA1) frequently functions as a transcriptional coactivator by directly binding to transcription factors and recruiting to the target gene promoters to promote gene transcription by increasing chromatin accessibility and promoting the formation of transcriptional complexes. In recent decades, various biological and pathological functions of SRC-1 have been reported, especially in the context of tumorigenesis. SRC-1 is a facilitator of the progression of multiple cancers, including breast cancer, prostate cancer, gastrointestinal cancer, neurological cancer, and female genital system cancer. The emerging multiorgan oncogenic role of SRC-1 is still being studied and may not be limited to only steroid hormone-producing tissues. Growing evidence suggests that SRC-1 promotes target gene expression by directly binding to transcription factors, which may constitute a novel coactivation pattern independent of AR or ER. In addition, the antitumour effect of pharmacological inhibition of SRC-1 with agents including various small molecules or naturally active compounds has been reported, but their practical application in clinical cancer therapy is very limited. For this review, we gathered typical evidence on the oncogenic role of SRC-1, highlighted its major collaborators and regulatory genes, and mapped the potential mechanisms by which SRC-1 promotes primary tumour progression.

LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer.

BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.

circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma.

As the most prominent RNA modification, N6-methyladenosine (m6 A) participates in the regulation of tumour initiation and progression. Circular RNAs (circRNAs) also play crucial roles in ubiquitous life processes. Whether circRNAs are required for m6 A regulation in renal cell carcinoma (RCC) remains unclear. Meta-analysis and bioinformatics identified that IGF2BP3 was upregulated in RCC and indicated a worse prognosis. IGF2BP3 significantly promoted RCC progression in vitro and in vivo. Mechanistically, circRARS bound to KH1-KH2 domains of IGF2BP3 to enhance m6 A modification recognition. A 12-nt sequence (GUCUUCCAGCAA) was proven to be the IGF2BP3-binding site of circRARS. Additionally, CAPN15, CD44, HMGA2, TNRC6A and ZMIZ2 were screened to be the target genes regulated by the IGF2BP3/circRARS complex in an m6 A-dependent manner. Stabiliser proteins, including HuR, Matrin3 and pAbPC1, were recruited by circRARS, thereby increasing the mRNA stability of the forementioned five target genes. Consequently, the IGF2BP3/circRARS complex facilitated the lipid accumulation of RCC cells and promoted sunitinib resistance via target genes. circRARS synergised with IGF2BP3 to facilitate m6 A recognition, thereby promoting RCC progression. Thus, IGF2BP3 could be a potential biomarker for RCC diagnosis and prognosis and a therapeutic target.

Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway.

BACKGROUND: The role of Tousled-like kinase 1 (TLK1) in in gastric cancer (GC) remains unclear. AIM: To investigate the expression, biological function, and underlying mechanisms of TLK1 in GC. METHODS: We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence, respectively. We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation, 5-ethynyl-2`-deoxyuridine, and Transwell assays as well as flow cytometry. We applied bioinformatics to elucidate the signaling pathways associated with TLK1. We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice. RESULTS: TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus. TLK1 knockdown significantly decreased colony formation, proliferation, invasion, and migration but increased apoptosis in GC cells. TLK1 overexpression had the opposite effects. Bioinformatics revealed, and subsequent experiments verified, that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression. The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC. CONCLUSION: The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is, therefore, promising as a therapeutic target against this disease.

Role of cancer-associated fibroblasts in the progression, therapeutic resistance and targeted therapy of oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumours with high morbidity and mortality. Although surgery, radiotherapy and chemotherapy are common treatment options available for oesophageal cancer, the 5-year survival rate remains low after treatment. On the one hand, many oesophageal cancers are are discovered at an advanced stage and, on the other hand, treatment resistance is a major obstacle to treating locally advanced ESCC. Cancer-associated fibroblasts (CAFs), the main type of stromal cell in the tumour microenvironment, enhance tumour progression and treatment resistance and have emerged as a major focus of study on targeted therapy of oesophageal cancer.With the aim of providing potential, prospective targets for improving therapeutic efficacy, this review summarises the origin and activation of CAFs and their specific role in regulating tumour progression and treatment resistance in ESCC. We also emphasize the clinical potential and emerging trends of ESCC CAFs-targeted treatments.

Progression of a corticotroph tumour during durable medical therapy with osilodrostat in a patient with persistent Cushing's disease.

Not required for Clinical Vignette.

LOXL2 in Cancer: A Two-Decade Perspective.

Lysyl Oxidase Like 2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises five lysine tyrosylquinone (LTQ)-dependent copper amine oxidases in humans. In 2003, LOXL2 was first identified as a promoter of tumour progression and, over the course of two decades, numerous studies have firmly established its involvement in multiple cancers. Extensive research with large cohorts of human tumour samples has demonstrated that dysregulated LOXL2 expression is strongly associated with poor prognosis in patients. Moreover, investigations have revealed the association of LOXL2 with various targets affecting diverse aspects of tumour progression. Additionally, the discovery of a complex network of signalling factors acting at the transcriptional, post-transcriptional, and post-translational levels has provided insights into the mechanisms underlying the aberrant expression of LOXL2 in tumours. Furthermore, the development of genetically modified mouse models with silenced or overexpressed LOXL2 has enabled in-depth exploration of its in vivo role in various cancer models. Given the significant role of LOXL2 in numerous cancers, extensive efforts are underway to identify specific inhibitors that could potentially improve patient prognosis. In this review, we aim to provide a comprehensive overview of two decades of research on the role of LOXL2 in cancer.

Differentiating tumour progression from pseudoprogression in glioblastoma patients: a monoexponential, biexponential, and stretched-exponential model-based DWI study.

BACKGROUND: To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients. METHODS: Forty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements. RESULTS: The values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88). CONCLUSIONS: Multi-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.

Vasculogenic Mimicry Occurs at Low Levels in Primary and Recurrent Glioblastoma.

Vasculogenic mimicry (VM), the ability of tumour cells to form functional microvasculature without an endothelial lining, may contribute to anti-angiogenic treatment resistance in glioblastoma. We aimed to assess the extent of VM formation in primary and recurrent glioblastomas and to determine whether VM vessels also express prostate-specific membrane antigen (PSMA), a pathological vessel marker. Formalin-fixed paraffin-embedded tissue from 35 matched pairs of primary and recurrent glioblastoma was immunohistochemically labelled for PSMA and CD34 and stained with periodic acid-Schiff (PAS). Vascular structures were categorised as endothelial vessels (CD34+/PAS+) or VM (CD34-/PAS+). Most blood vessels in both primary and recurrent tumours were endothelial vessels, and these significantly decreased in recurrent tumours (p < 0.001). PSMA was expressed by endothelial vessels, and its expression was also decreased in recurrent tumours (p = 0.027). VM was observed in 42.86% of primary tumours and 28.57% of recurrent tumours. VM accounted for only a small proportion of the tumour vasculature and VM density did not differ between primary and recurrent tumours (p = 0.266). The functional contribution of VM and its potential as a treatment target in glioblastoma require further investigation.