Biological Behavior Of Tumor Research Articles

Relation of FDG uptake of breast cancer and the histologic and the biologic characteristics of the tumor

Abstract Background Breast cancer is considered the most common type of cancer and the second leading cause of cancer-related death among women. The prognostic factors including histological type, tumor nuclear grade, tumor size, and preoperative tumor-nodes-metastasis (TNM), hormone receptor and immunohistochemical molecular markers in the specimens, define the prognosis and survival rate. Early diagnosis and accurate follow-up of these patients affect the management. 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) has proved to be an effective and accurate imaging technique for a variety of diagnostic oncology tasks in breast cancer, lymph node staging, staging and restaging of recurrent and metastatic disease, and treatment follow up. Sufficient knowledge of the initial characteristics of breast tumors that may affect 18F-FDG uptake is essential for optimal use and interpretation of 18FFDG PET/CT imaging. Several pioneering studies have investigated the correlation between the affinity to 18F-FDG uptake and some of the histological and biological characteristics such as tumor type, grade, hormonal receptor status and HER2 status. Objective To correlate the relation of 18F-fluoro-2-deoxy-D-gIucose (18F-FDG) positron emission tomography/ computed tomography (PET/CT) uptake in breast cancer to histopathological and biological characteristics. Methods A prospective descriptive study over the course of 6 months from August 2019 till February 2020. It included twenty five patients with pathologically proven breast carcinoma referred to the Radiology department, Ain Shams University Hospitals/ Private centers for a preoperative 18FDG PET/CT scan. Results For the tumors in 25 women, the mean SUVmax was 4.75±2.55. Primary tumor 18FFDG uptake ratio was correlated with patients' age (P = 0.032), tumor size (P = 0.034), histological grade (P=O.OI 8), estrogen and progesterone negativity (P = 0.012), Her2/neu positivity (P = 0.012), high Ki-67 level (>10%) (P = 0.024), axillary lymph node involvement (P = 0.038) and distant metastasis (P = 0.039). High Ki-67 level (Pearson Correlation Coefficient= 0.457; 95% confidence interval; P = 0.037) and tumor size (Pearson Correlation Coefficient =0.458; 95% confidence interval, P = 0.021) were determining factors for high 18F-FDG uptake values. The histological type (P = 0.525) was not significantly correlated with 18F-FDG uptake. Conclusion FDG PET imaging was used to estimate tumor biologic behavior of breast cancer such as histopathologic grading, immunohistochemistry, axillary lymph node status and distant metastasis. SUVmax correlated with several of pathological prognostic factors may have potential for predicting the prognosis of breast cancer. 18F-FDG PET/CT could be a useful tool to pretherapeutically predict biological characteristics and baseline risk of breast cancer Increased 18FFDG uptake on PET/CT was correlated with a high Ki-67 proliferation index and larger tumor size. These results suggest a potential role of 18F-FDG PET/CT in identifying tumor aggressiveness.

High FITM2 expression promotes cell migration ability of hepatocellular carcinoma by regulating the formation of caveolae and indicates poor patient survival.

Hepatocellular carcinoma (HCC) is among the most malignant tumors with high recurrence and low 5-year survival rate. Lipid metabolism is essential in tumor metastasis, although how altered lipid metabolism promotes HCC progression has not been well elucidated. Fat Storage Inducing Transmembrane Protein 2 (FITM2) is a gene involved in lipid homeostasis and cytoskeletal organization; however, its role in regulating tumor biological behavior has not been evaluated. In this study, immunohistochemistry was performed to evaluate the expression of FITM2 in HCC. Univariate and multivariate analysis was performed to identify the prognostic factors. RNA interference wound healing and transwell experiments were performed to analyze the biological role of FITM2. Western blot analysis was performed to investigate the potential downstream signaling. The results revealed that FITM2 was highly expressed in the intratumoral tissues of HCC. Expression of intratumoral FITM2 was associated with microvascular invasion. FITM2 is an independent risk factor of HCC disease-free survival and overall survival. In vitro studies revealed that knockdown of FITM2 significantly inhibited the migration ability of HCC cells. FITM2 promotes HCC cell migration by regulating the expression of caveolin-1 and promoting the formation of caveolae. These results indicate that high intratumoral expression of FITM2 is associated with poor HCC prognosis, which may be applied to develop a new adjuvant therapy.

Metabolic Tumor Microenvironment Characterization of Contrast Enhancing Brain Tumors Using Physiologic MRI.

The tumor microenvironment is a critical regulator of cancer development and progression as well as treatment response and resistance in brain neoplasms. The available techniques for investigation, however, are not well suited for noninvasive in vivo characterization in humans. A total of 120 patients (59 females; 61 males) with newly diagnosed contrast-enhancing brain tumors (64 glioblastoma, 20 brain metastases, 15 primary central nervous system (CNS) lymphomas (PCNSLs), and 21 meningiomas) were examined with a previously established physiological MRI protocol including quantitative blood-oxygen-level-dependent imaging and vascular architecture mapping. Six MRI biomarker maps for oxygen metabolism and neovascularization were fused for classification of five different tumor microenvironments: glycolysis, oxidative phosphorylation (OxPhos), hypoxia with/without neovascularization, and necrosis. Glioblastoma showed the highest metabolic heterogeneity followed by brain metastasis with a glycolysis-to-OxPhos ratio of approximately 2:1 in both tumor entities. In addition, glioblastoma revealed a significant higher percentage of hypoxia (24%) compared to all three other brain tumor entities: brain metastasis (7%; p < 0.001), PCNSL (8%; p = 0.001), and meningioma (8%; p = 0.003). A more aggressive biological brain tumor behavior was associated with a higher percentage of hypoxia and necrosis and a lower percentage of remaining vital tumor tissue and aerobic glycolysis. The proportion of oxidative phosphorylation, however, was rather similar (17–26%) for all four brain tumor entities. Tumor microenvironment (TME) mapping provides insights into neurobiological differences of contrast-enhancing brain tumors and deserves further clinical cancer research attention. Although there is a long roadmap ahead, TME mapping may become useful in order to develop new diagnostic and therapeutic approaches.

CKAP2L, as an Independent Risk Factor, Closely Related to the Prognosis of Glioma.

Recent studies have found that cytoskeleton-associated protein 2 like (CKAP2L), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and CKAP2L expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. CKAP2L expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of CKAP2L was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that CKAP2L can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that CKAP2L may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on CKAP2L were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.

What Mediates Fibrosis in the Tumor Microenvironment of Clear Renal Cell Carcinoma.

Previous studies have demonstrated that direct targeting of interstitial cancer-associated fibroblasts (CAF) and tumor fibrosis alone seemed to be an unpromising treatment option for malignant tumors. Therefore, it is necessary to further explore the mechanism of the influence of collagen and tumor fibrosis on the biological behavior of malignant tumors. The current study aimed to explore the effect of intratumor fibrosis on the prognosis of renal clear cell carcinoma (ccRCC) and its mechanism. With the bioinformatic analysis of The Cancer Genome Atlas (TCGA) database (n = 537), the study showed that high Collagen type I α 1 (COL1A1) mRNA expression indicated the poor prognosis of ccRCC patients compared with low expression ones. We further used the Two-photon-excited fluorescence (TPEF)/second harmonic generation (SHG) microscopy to determine the intratumor fibrosis of 68 patients with surgical resection of ccRCC and confirmed that a high fibrosis level in the tumor was associated with a poor prognosis compared with patients with low expression (Progression-Free Survival: p = 0.030). We further measured the protein chips of 640 cytokines in ccRCC specimens and found that several cytokines, including prolactin (PRL), were associated with the degree of fibrosis in the tumor, as confirmed by the prolactin receptor (PRLR) immunohistochemical method. In addition, the study showed that PRLR expression decreased significantly in the ccRCC compared with adjacent normal tissue (p < 0.05). Our research shows that low expression of PRLR predicted the poor survival of the patient. We used the Cell Counting Kit-8 experiment, the transwell and the plate clone formation assay to evaluate the role of PRL in the 7860 and the ACHN cell lines. We found that PRL promoted ccRCC cell proliferation and migration. JAK-STAT3 activation was found in the high prolactin expression group by mass spectrum analysis. This study delineated the fibrosis-based tumor microenvironment characteristics of ccRCC. PRL/PRLR may be involved in the fibrosis process and are essential prognostic risk factors for ccRCC.

Cell-to-cell contact-mediated regulation of tumor behavior in the tumor microenvironment.

Tumor growth and progression are complex processes mediated by mutual interactions between cancer cells and their surrounding stroma that include diverse cell types and acellular components, which form the tumor microenvironment. In this environment, direct intercellular communications play important roles in the regulation of the biological behaviors of tumors. However, the underlying molecular mechanisms are insufficiently defined. We used an in vitro coculture system to identify genes that were specifically expressed at higher levels in cancer cells associated with stromal cells. Major examples included epithelial membrane protein 1 (EMP1) and stomatin, which positively and negatively regulate tumor progression, respectively. EMP1 promotes tumor cell migration and metastasis via activation of the small GTPase Rac1, while stomatin strongly suppresses cell proliferation and induces apoptosis of cancer cells via inhibition of Akt signaling. Here we highlight important aspects of EMP1, stomatin, and their family members in cancer biology. Furthermore, we consider the molecules that participate in intercellular communications and signaling transduction between cancer cells and stromal cells, which may affect the phenotypes of cancer cells in the tumor microenvironment.

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors.

The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches. Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3 (B7-H3) among the most common cancers of the GIT, including CRC, GC, and EC, whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal. This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms, and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways, such as Janus kinase 2/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB. B7-H3 exerts an important role in progression, metastasis and resistance to anticancer therapy in these tumors. In addition, the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response. Accordingly, it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response, impaired tumor progression, invasion, angiogenesis, and metastasis and decreased resistance to anticancer therapy. Finally, the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis. In this review, we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs.

Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide (VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.

Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice

The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients’ tumors. The evolution of metabolic changes, followed in vivo longitudinally by 1H Magnetic Resonance Spectroscopy (1H MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients’ tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell–cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression in the non-enhancing infiltration zone of glioblastoma.

The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis.

A wealth of evidence supports an association between physical exercise, decreased tumor growth rate, and reduced risk of cancer mortality. In this context, the tumor vascular microenvironment may play a key role in modulating tumor biologic behavior. The present systematic review and meta-analysis aimed to summarize the evidence regarding the effects of physical exercise on tumor vasculature in pre-clinical studies. We performed a computerized research on the PubMed, Scopus, and EBSCO databases to identify pre-clinical studies that evaluated the effect of physical exercise on tumor vascular outcomes. Mean differences were calculated through a random effects model. The present systematic review included 13 studies involving 373 animals. From these, 11 studies evaluated chronic intratumoral vascular adaptations and 2 studies assessed the acute intratumoral vascular adaptations to physical exercise. The chronic intratumoral vascular adaptations resulted in higher tumor microvessel density in 4 studies, increased tumor perfusion in 2 studies, and reduced intratumoral hypoxia in 3 studies. Quantitatively, regular physical exercise induced an increased tumor vascularization of 2.13 [1.07, 3.20] (p<0.0001). The acute intratumoral vascular adaptations included increased vascular conductance and reduced vascular resistance, which improved tumor perfusion and attenuated intratumoral hypoxia. In pre-clinical studies, physical exercise seems to improve tumor vascularization.

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis.

Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.

Emerging applications of radiomics in rectal cancer: State of the art and future perspectives

Rectal cancer (RC) is the third most commonly diagnosed cancer and has a high risk of mortality, although overall survival rates have improved. Preoperative assessments and predictions, including risk stratification, responses to therapy, long-term clinical outcomes, and gene mutation status, are crucial to guide the optimization of personalized treatment strategies. Radiomics is a novel approach that enables the evaluation of the heterogeneity and biological behavior of tumors by quantitative extraction of features from medical imaging. As these extracted features cannot be captured by visual inspection, the field holds significant promise. Recent studies have proved the rapid development of radiomics and validated its diagnostic and predictive efficacy. Nonetheless, existing radiomics research on RC is highly heterogeneous due to challenges in workflow standardization and limitations of objective cohort conditions. Here, we present a summary of existing research based on computed tomography and magnetic resonance imaging. We highlight the most salient issues in the field of radiomics and analyze the most urgent problems that require resolution. Our review provides a cutting-edge view of the use of radiomics to detect and evaluate RC, and will benefit researchers dedicated to using this state-of-the-art technology in the era of precision medicine.

A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.

MicroRNA-203-3p inhibits the proliferation, invasion and migration of pancreatic cancer cells by downregulating fibroblast growth factor 2.

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3′-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.

Prognostic Value Of Vascular Invasion In Breast Tumours In She-Dogs (Pilot Study)

Breast tumours are the most common neoplasm in intact she-dogs. However, breast tumours in she-dogs differ significantly in morphological features and biological behaviour, so the definition of prognostic factors is relevant. A study on tumour cell dissemination in breast tumours in she-dogs by migration of these cells into blood and lymphatic vessels depending on their histological characteristics and disease stage was conducted. The study of the problem was performed on the basis of the clinic of modern veterinary medicine “Best” in Zaporizhzhia. She-dogs with breast neoplasms of different ages and breeds were used as objects in the proven absence of signs of metastatic lesions of other organs and tissues, including lungs, abdominal organs and bones. The presence of cancer cells in the vessels was determined by the tumour clots formed by them, fixed to the endothelium. The study revealed the presence of angioinvasion regardless of the clinical stage of the tumour process. In this case, the dissemination of tumour cells by migration into lymphatic vessels was observed only in the second clinical stage of breast tumours. In patients with stage 1 breast cancer in the vast majority of cases (66.7% of patients) angioinvasion is registered in the micropapillary invasive carcinomas (ICD-O code 8507/2). Tumour cells in blood vessels were verified in simple cribriform carcinoma (ICD-O code 8201/3) in more than 80% of she-dogs with stage 3 breast cancer. In contrast to the above groups, in patients with stage 2 cancer, migration of tumour cells into both blood and lymphatic vessels was found. Most often the signs of angio- and lymphoinvasion were found in invasive carcinoma mixed type (ICD-O code 8562/3), tubulopapillary carcinoma (ICD-O code 8503/3), and tubular carcinoma (ICD-O code 8211/3) ‒ in 34.1% and 36.8%, 19.3% and 26.3%, 17.0% and 10.5% of cases, respectively. The obtained results allow predicting the probability of penetration of tumour cells into blood and lymphatic vessels with a high degree of reliability, which in the future can better predict the biological behaviour of breast tumours

STK10 knockout inhibits cell migration and promotes cell proliferation via modulating the activity of ERM and p38 MAPK in prostate cancer cells.

Prostate cancer (PCa) is one of the most common types of cancer and is a serious threat to men's health due to the high rate of incidence and metastasis. However, the exact underlying pathology of this malignant disease has yet to be fully elucidated. The ezrin-radixin-moesin (ERM) family of proteins are associated with the development and metastasis of various types of cancer. Serine threonine kinase 10 (STK10) is an ERM kinase that is involved in the activation of ERM proteins and serves essential roles in the aggregation and adhesion of lymphocytes. To evaluate the functional roles of STK10 in the pathogenesis of PCa, a STK10-knockout (KO) DU145 PCa cell line was generated using the CRISPR-Cas9 gene editing system, and the effects of STK10 deletion on tumor biological behaviors were further analyzed. The present data suggested that STK10 KO promoted PCa cell proliferation by inhibiting p38 MAPK activation and suppressed migration primarily via the inhibition of p38 MAPK signaling and ERM protein activation. To the best of our knowledge, this is the first study to provide evidence that STK10 plays important roles in the proliferation and migration of PCa cells, which will be useful for further investigation into the pathogenesis of this disease.

Whole Tumor Capsule Is Prognostic of Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer.

Tumor capsule integrity is becoming a relevant issue to predict the biological behavior of human tumors, including thyroid cancer. This work aims to verify whether a whole tumor capsule in the classical variant of papillary thyroid carcinoma (CVPTC) could have as a predictive role of a good outcome as for follicular variant (FVPTC). FVPTC (n = 600) and CVPTC (n = 554) cases were analyzed. We distinguished between encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and noninvasive (En-FVPTC and En-CVPTC) tumors, according to the invasion or integrity of the tumor capsule, respectively. Cases without a tumor capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). The subgroup of each variant was evaluated for BRAF mutations. E-FVPTC was more frequent than E-CVPTC (P < .001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. A total of 177 of 614 (28.8%) cases were BRAFV600E mutated, and 10 of 614 (1.6%) carried BRAF-rare alterations. A significantly higher rate of En-CVPTC (22/49, 44.9%) than En-FVPTC (15/195, 7.7%) (P < .0001) were BRAFV600E mutated. En-CVPTC is less prevalent than En-FVPTC. However, it has good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumor capsule in CVPTC as well. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (ie, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NIFTP) could be envisaged.

Diffuse neurofibroma of the chest and abdominal wall invading the diaphragm leads to diaphragmatic eventration: case report

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant condition with a high rate of new mutation and variable expression. Diffuse neurofibroma of the epidermis invading deeper organs is rare.We report a case of diffuse subcutaneous neurofibroma in the thoracoabdominal wall which had invaded the diaphragm and caused diaphragmatic eventration.Case presentationWe describe a patient with diffuse neurofibroma of the chest and abdomen who was admitted to the hospital due to sudden abdominal pain and a possible diaphragmatic hernia. We performed thoracotomy and found that the neurofibroma had invaded the diaphragm and caused diaphragmatic eventration.ConclusionsThis occurrence has not been reported, and it shows that although neurofibromatosis is a benign disease, it still has the biological behavior of a malignant tumor and may cause a serious impact on and damage to other organs.

Driver Gene Mutations and Risk of Lymph Node Metastasis in Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer (NSCLC) lymph node status is closely related to its diagnosis, treatment, and prognosis. The lymph node status is an important basis for formulating clinical treatment strategies of NSCLC, therefore comprehensive and profound understanding of risk factors for lymph node metastasis is essential. There are many known factors for lymph node metastasis in NSCLC, such as pathological subtypes, tumor size, tumor location. Meanwhile, whether the mutation of the driver gene affects the lymph node metastasis is still lacking enough research. This article aims to elaborate the relationship between NSCLC driver gene mutation and lymph node metastasis, from NSCLC lymph node metastasis-related risk factors, driver genes and lymph node metastasis, metastatic lymph node mutation status analysis and detection these several aspects to summarize the latest research progress in NSCLC driver gene mutation and lymph node metastasis risk. It also fully explained the correlation between driver gene mutations and NSCLC tumor biological behaviors such as lymph node metastasis.

Identification, Validation, and Utilization of Immune Cells in Pancreatic Ductal Adenocarcinoma Based on Marker Genes.

The immune response affects tumor biological behavior and progression. The specific immune characteristics of pancreatic ductal adenocarcinoma (PDAC) can determine the metastatic abilities of cancerous cells and the survival of patients. Therefore, it is important to characterize the specific immune landscape in PDAC tissue samples, and the effect of various types of therapy on that immune composition. Previously, a set of marker genes was identified to assess the immune cell composition in different types of cancer tissue samples. However, gene expression and subtypes of immune cells may vary across different types of cancers. The aim of this study was to provide a method to identify immune cells specifically in PDAC tissue samples. The method is based on defining a specific set of marker genes expressed by various immune cells in PDAC samples. A total of 90 marker genes were selected and tested for immune cell type-specific definition in PDAC; including 43 previously used, and 47 newly selected marker genes. The immune cell-type specificity was checked mathematically by calculating the “pairwise similarity” for all candidate genes using the PDAC RNA-sequenced dataset available at The Cancer Genome Atlas. A set of 55 marker genes that identify 22 different immune cell types for PDAC was created. To validate the method and the set of marker genes, an independent mRNA expression dataset of 24 samples of PDAC patients who received various types of (neo)adjuvant treatments was used. The results showed that by applying our method we were able to identify PDAC specific marker genes to characterize immune cell infiltration in tissue samples. The method we described enabled identifying different subtypes of immune cells that were affected by various types of therapy in PDAC patients. In addition, our method can be easily adapted and applied to identify the specific immune landscape in various types of tissue samples.