Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma: A report of 3 cases and literature review. / Epstein-Barrç— æ¯’ç›¸å ³æ·‹å·´ä¸Šçš®ç˜¤æ ·è‚å† èƒ†ç®¡ç™Œ3ä¾‹å¹¶æ–‡çŒ®å¤ä¹ ï¼ˆè‹±æ–‡ï¼‰.

Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.

Integrative analysis identifies molecular features of fibroblast and the significance of fibrosis on neoadjuvant chemotherapy response in breast cancer.

BACKGROUND: The molecular features of fibroblasts and the role of fibrosis in neoadjuvant chemotherapy (NAC) response and breast cancer (BRCA) prognosis remain unclear. Therefore, this study aimed to investigate the impact of interstitial fibrosis on the response and prognosis of patients with BRCA undergoing NAC treatment. MATERIALS AND METHODS: The molecular characteristics of pathologic complete response (pCR) and non-pCR (npCR) in patients with BRCA were analyzed using multiomics analysis. A clinical cohort was collected to investigate the predictive value of fibrosis in patients with BRCA. RESULTS: Fibrosis-related signaling pathways were significantly upregulated in patients with npCR. npCR may be associated with distinct and highly active fibroblast subtypes. Patients with high fibrosis had lower pCR rates. The fibrosis-dependent nomogram for pCR showed efficient predictive ability [training set: area under the curve [AUC]=0.871, validation set: AUC=0.792]. Patients with low fibrosis had a significantly better prognosis than those with high fibrosis, and those with a high fibrotic focus index had significantly shorter overall and recurrence-free survival. Therefore, fibrosis can be used to predict pCR. Our findings provide a basis for decision-making in the treatment of BRCA. CONCLUSIONS: npCR is associated with a distinct and highly active fibroblast subtype. Furthermore, patients with high fibrosis have lower pCR rates and shorter long-term survival. Therefore, fibrosis can predict pCR. A nomogram that includes fibrosis can provide a basis for decision-making in the treatment of BRCA.

Mitochondria-related chemoradiotherapy resistance genes-based machine learning model associated with immune cell infiltration on the prognosis of esophageal cancer and its value in pan-cancer.

Esophageal cancer, known for its high incidence and low five-year survival rate, poses significant treatment challenges. A key aspect of this challenge is the close link between mitochondria and resistance to chemoradiotherapy (CRT). Currently, there is a scarcity of biomarkers for predicting CRT response and prognosis in esophageal cancer. Our study addresses this gap by developing a prognostic model that incorporates mitochondria-related CRT resistance (MRCRTR) genes, including CTSL, TBL1X, CLN8, MMP1, PDPN, and MRPL37. Survival analysis using Kaplan-Meier curves reveals that patients with high MRCRTR scores have lower survival rates than those with low scores. Utilizing a nomogram, we successfully predict the one-, two-, and three-year overall survival rates for esophageal cancer patients. Cox regression analysis confirms the MRCRTR score as an independent prognostic factor. Furthermore, our single-cell and correlation analyses suggested that MRCRTR genes might influence CRT resistance by modulating the immune microenvironment and impacting angiogenesis. Our pan-cancer analysis also indicates the potential applicability of MRCRTR scores to head and neck squamous cell carcinoma. The validation of these findings, conducted with samples from Xiang-ya Hospital, aligns closely with our bioinformatics results. Our study not only explores the role of MRCRTR genes in predicting the prognosis of esophageal cancer but also enhances the understanding of the interplay between CRT, mitochondria, and patient outcomes.

STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.

BACKGROUND: Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted. METHODS: In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC. RESULTS: Analysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients (p < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells. CONCLUSIONS: STK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.

Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.

Emerging roles of ferroptosis-related miRNAs in tumor metastasis.

Ferroptosis, a novel mode of cell death dependent on iron and reactive oxygen species, has been extensively explored during malignant tumors metastasis. Ferroptosis can interact with multiple components of the tumor microenvironment to regulate metastasis. These interactions generally include the following aspects: (1) Epithelial-mesenchymal transformation, which can help cancer cells increase their sensitivity to ferroptosis while they have multiple mechanisms to fight against it; (2) Disorder of iron metabolism in cancer stem cells which maintains their stem characteristics; (3) Polarization of M0 macrophages to M2. (4) The paradoxical effects of iron metabolism and CD8 + T cells induced by ferroptosis (5) Regulation of angiogenesis. In addition, ferroptosis can be regulated by miRNAs through the reprogramming of various intracellular metabolism processes, including the regulation of the glutathione- glutathione peroxidase 4 pathway, glutamic acid/cystine transport, iron metabolism, lipid metabolism, and oxidative stress. Therefore, there are many potential interactions between ferroptosis-related miRNAs and tumor metastasis, including interaction with cancer cells and immune cells, regulating cytokines, and angiogenesis. This review focuses on the role of ferroptosis-related miRNA in tumor metastasis, aiming to help readers understand their relationship and provide a new perspective on the potential treatment strategies of malignant tumors.

Crosstalk between N6-methyladenosine (m6A) modification and noncoding RNA in tumor microenvironment.

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes, and it participates in the regulation of pathophysiological processes in various diseases, including malignant tumors, by regulating the expression and function of both coding and non-coding RNAs (ncRNAs). More and more studies demonstrated that m6A modification regulates the production, stability, and degradation of ncRNAs and that ncRNAs also regulate the expression of m6A-related proteins. Tumor microenvironment (TME) refers to the internal and external environment of tumor cells, which is composed of numerous tumor stromal cells, immune cells, immune factors, and inflammatory factors that are closely related to tumors occurrence and development. Recent studies have suggested that crosstalk between m6A modifications and ncRNAs plays an important role in the biological regulation of TME. In this review, we summarized and analyzed the effects of m6A modification-associated ncRNAs on TME from various perspectives, including tumor proliferation, angiogenesis, invasion and metastasis, and immune escape. Herein, we showed that m6A-related ncRNAs can not only be expected to become detection markers of tumor tissue samples, but can also be wrapped into exosomes and secreted into body fluids, thus exhibiting potential as markers for liquid biopsy. This review provides a deeper understanding of the relationship between m6A-related ncRNAs and TME, which is of great significance to the development of a new strategy for precise tumor therapy.

Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma.

Background: The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC. Methods: We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape. Results: The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues. Conclusion: SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

Successful management of a rare radius schwannoma mimicking malignant bone tumors: A case report and literature review.

Background: Schwannomas are benign tumors originating from Schwann cells, frequently occurring in the spinal cord and peripheral nerves. Intraosseous schwannomas, a rare subset, account for approximately 0.2% of schwannomas. Intraosseous schwannomas commonly impinge the mandible, followed by the sacrum and the spine. By far, only three cases of radius intraosseous schwannomas have been reported in PubMed. The tumor was treated differently in all three cases, resulting in different outcomes. Case presentation: A 29-year-old male construction engineer who complained of a painless mass on the radial aspect of the right forearm was diagnosed with an intraosseous schwannoma of the radius based on radiography, three-dimensional computed tomography reconstruction, magnetic resonance imaging, pathological examination, and immunohistochemistry. A different surgical approach was employed to reconstruct the radial graft defect using bone microrepair techniques, resulting in more reliable bone healing and early functional recovery. Meanwhile, no clinical and radiographic findings suggestive of recurrence were observed at the 12-month follow-up. Conclusion: Vascularized bone flap transplantation combined with three-dimensional imaging reconstruction planning might yield better results for repairing small segmental bone defects of the radius caused by intraosseous schwannomas.

Clinical features and imaging manifestations for intravascular large B-cell lymphoma. / è¡€ç®¡å† å¤§B细胞淋巴瘤的临床特点及影像学表现.

OBJECTIVES: Intravascular large B-cell lymphomas are a rare group of extranodal non-Hodgkin's lymphomas with no apparent specificity of symptoms and often a poor prognosis. This study aims to investigate the clinical features and imaging manifestations of intravascular large B-cell lymphoma, to improve the awareness of clinicians and imaging physicians and to reduce the underdiagnosis and misdiagnosis of this disease. METHODS: Five patients with pathologically confirmed intravascular large B-cell lymphoma diagnosed between December 2011 and February 2022 at Xiangya Hospital of Central South University were retrospectively analyzed for clinical features and imaging manifestations. RESULTS: The age range for the 5 patients in this paper was 44-72 years at an average of (55.4±11.2) years, 2 were male and 3 were female. There were 4 patients with fever, 3 patients with cough, 3 patients with fatigue, and 2 patients with neurological symptoms. The primary sites of lesions were bilateral adrenal glands (2 cases), liver (1 case), central nervous system (1 case), lung (1 case). Imaging of the corresponding site was performed in 5 cases. When the primary site is the adrenal gland, it appears as bilateral adrenal masses or bilateral adrenal thickening with clear contours. When the primary site is the liver, it appears as a hypodense lesion in the right lobe of the liver with "vascular floating sign". When the primary site is the central nervous system, it appears as multiple tumor-like lesions in the frontal-parietal-occipital lobe, right temporal lobe and bilateral cerebellar hemispheres with multiple hemorrhages within the lesions. When the primary site is the lung, it appears as multiple ground glass shadows and solid changes in both lungs with localized lobular septal thickening. The final pathological diagnosis was intravascular large B-cell lymphoma in all 5 patients, one of whom had a good prognosis after chemotherapy, 2 of whom died within 3 days of discharge, and two of whom were lost to follow-up. CONCLUSIONS: Intravascular large B-cell lymphoma can involve multiple tissues and organs, and its prognosis is often poor, and its imaging manifestations possess certain specificity. When this disease is highly suspected, a biopsy of the corresponding organ should be performed as soon as possible to clarify the diagnosis.

Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma.

Background: The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood. Methods: In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape. Results: The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers. Conclusions: GSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

Lipid nanoparticle-based mRNA vaccines in cancers: Current advances and future prospects.

Messenger RNA (mRNA) vaccines constitute an emerging therapeutic method with the advantages of high safety and efficiency as well as easy synthesis; thus, they have been widely used in various human diseases, especially in malignant cancers. However, the mRNA vaccine technology has some limitations, such as instability and low transitive efficiency in vivo, which greatly restrict its application. The development of nanotechnology in the biomedical field offers new strategies and prospects for the early diagnosis and treatment of human cancers. Recent studies have demonstrated that Lipid nanoparticle (LNP)-based mRNA vaccines can address the poor preservation and targeted inaccuracy of mRNA vaccines. As an emerging cancer therapy, mRNA vaccines potentially have broad future applications. Unlike other treatments, cancer mRNA vaccines provide specific, safe, and tolerable treatments. Preclinical studies have used personalized vaccines to demonstrate the anti-tumor effect of mRNA vaccines in the treatment of various solid tumors, including colorectal and lung cancer, using these in a new era of therapeutic cancer vaccines. In this review, we have summarized the latest applications and progress of LNP-based mRNA vaccines in cancers, and discussed the prospects and limitations of these fields, thereby providing novel strategies for the targeted therapy of cancers.

Case Report: Intravascular Large B-Cell Lymphoma: A Clinicopathologic Study of Four Cases With Review of Additional 331 Cases in the Literature.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and highly malignant non-Hodgkin B-cell lymphoma with uncommon clinical presentation and poor prognosis. The diagnostic pitfall of IVLBCL is mainly due to the fact that subtle histological changes could be easily overlooked, in addition to its rare occurrence, non-specific and variable clinical presentations, and the absence of significant mass lesions. The purpose of this study is to further explore the clinicopathologic and molecular features of IVLBCL to ensure an accurate diagnosis of this entity. Here, we retrospectively present the data of the four new cases and the literature cases. The age ranged from 23 to 92, with a medium age of 67 and a male-to-female ratio of 1:1. The clinical manifestations are extremely variable, including fever, night sweats, weight loss, anemia, thrombocytopenia, unexplained hypoxemia, impaired consciousness, and skin lesions, as well as the extremely low levels of serum albumin, high levels of serum lactate dehydrogenase (LDH), soluble interleukin-2 receptor (sIL2R), and ferritin. Morphologically, 99.9% of cases showed a selective growth pattern with large, atypical lymphocytes within the lumen of small blood vessels. In addition, vast majority of cases were positive for CD20, CD79a, PAX5, MUM1, and BCL6, and a subset of cases expressed BCL2 and CD5, whereas CD3 and CD10 were typically negative. Ki-67 proliferative index ranged from 20% to 100%. To sum up, we have conducted comprehensive case reports, to the best of our knowledge, this is the largest reported cohort of IVLBCL cases. Comprehensive assessments and more IVLBCL cases are required for early diagnosis and prompt treatment.

Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis.

Single-cell sequencing (SCS) is an emerging high-throughput technology that can be used to study the genomics, transcriptomics, and epigenetics at a single cell level. SCS is widely used in the diagnosis and treatment of various diseases, including cancer. Over the years, SCS has gradually become an effective clinical tool for the exploration of tumor metastasis mechanisms and the development of treatment strategies. Currently, SCS can be used not only to analyze metastasis-related malignant biological characteristics, such as tumor heterogeneity, drug resistance, and microenvironment, but also to construct metastasis-related cell maps for predicting and monitoring the dynamics of metastasis. SCS is also used to identify therapeutic targets related to metastasis as it provides insights into the distribution of tumor cell subsets and gene expression differences between primary and metastatic tumors. Additionally, SCS techniques in combination with artificial intelligence (AI) are used in liquid biopsy to identify circulating tumor cells (CTCs), thereby providing a novel strategy for treating tumor metastasis. In this review, we summarize the potential applications of SCS in the field of tumor metastasis and discuss the prospects and limitations of SCS to provide a theoretical basis for finding therapeutic targets and mechanisms of metastasis.

Emerging Role of Cancer-Associated Fibroblasts-Derived Exosomes in Tumorigenesis.

Cancer-associated fibroblasts (CAFs) are the most important component of the stromal cell population in the tumor microenvironment and play an irreplaceable role in oncogenesis and cancer progression. Exosomes, a class of small extracellular vesicles, can transfer biological information (e.g., proteins, nucleic acids, and metabolites as messengers) from secreting cells to target recipient cells, thereby affecting the progression of human diseases, including cancers. Recent studies revealed that CAF-derived exosomes play a crucial part in tumorigenesis, tumor cell proliferation, metastasis, drug resistance, and the immune response. Moreover, aberrant expression of CAF-derived exosomal noncoding RNAs and proteins strongly correlates with clinical pathological characterizations of cancer patients. Gaining deeper insight into the participation of CAF-derived exosomes in tumorigenesis may lead to novel diagnostic biomarkers and therapeutic targets in human cancers.