Structure-aware deep model for MHC-II peptide binding affinity prediction.

The prediction of major histocompatibility complex (MHC)-peptide binding affinity is an important branch in immune bioinformatics, especially helpful in accelerating the design of disease vaccines and immunity therapy. Although deep learning-based solutions have yielded promising results on MHC-II molecules in recent years, these methods ignored structure knowledge from each peptide when employing the deep neural network models. Each peptide sequence has its specific combination order, so it is worth considering adding the structural information of the peptide sequence to the deep model training. In this work, we use positional encoding to represent the structural information of peptide sequences and validly combine the positional encoding with existing models by different strategies. Experiments on three datasets show that the introduction of position-coding information can further improve the performance built upon the existing model. The idea of introducing positional encoding to this field can provide important reference significance for the optimization of the deep network structure in the future.

A novel model for predicting postoperative liver metastasis in R0 resected pancreatic neuroendocrine tumors: integrating computational pathology and deep learning-radiomics.

BACKGROUND: Postoperative liver metastasis significantly impacts the prognosis of pancreatic neuroendocrine tumor (panNET) patients after R0 resection. Combining computational pathology and deep learning radiomics can enhance the detection of postoperative liver metastasis in panNET patients. METHODS: Clinical data, pathology slides, and radiographic images were collected from 163 panNET patients post-R0 resection at Fudan University Shanghai Cancer Center (FUSCC) and FUSCC Pathology Consultation Center. Digital image analysis and deep learning identified liver metastasis-related features in Ki67-stained whole slide images (WSIs) and enhanced CT scans to create a nomogram. The model's performance was validated in both internal and external test cohorts. RESULTS: Multivariate logistic regression identified nerve infiltration as an independent risk factor for liver metastasis (p < 0.05). The Pathomics score, which was based on a hotspot and the heterogeneous distribution of Ki67 staining, showed improved predictive accuracy for liver metastasis (AUC = 0.799). The deep learning-radiomics (DLR) score achieved an AUC of 0.875. The integrated nomogram, which combines clinical, pathological, and imaging features, demonstrated outstanding performance, with an AUC of 0.985 in the training cohort and 0.961 in the validation cohort. High-risk group had a median recurrence-free survival of 28.5 months compared to 34.7 months for the low-risk group, showing significant correlation with prognosis (p < 0.05). CONCLUSION: A new predictive model that integrates computational pathologic scores and deep learning-radiomics can better predict postoperative liver metastasis in panNET patients, aiding clinicians in developing personalized treatments.

Prostate cancer-associated transcript 6 (PCAT6) promotes epithelial-mesenchymal transition and stemness and worsens prognosis in patients with colorectal cancer.

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

Transcriptomic characterization and construction of M2 macrophage-related prognostic and immunotherapeutic signature in ovarian metastasis of gastric cancer.

BACKGROUND: Ovarian metastasis (OM) poses a major threat to the outcome of gastric cancer (GC) patients. Recently, immunotherapy emerged as a novel promising therapeutic strategy to treat late-stage GC, whereas its efficacy is influenced by tumor immune microenvironment (TIME). M2 macrophage, a key subset within TIME, plays dual immunosuppressive and pro-tumorigenic roles in cancer progression and is recognized as a potential therapeutic target. However, molecular mechanisms underlying OM remain elusive and the TIME-related prognostic and immunotherapeutic index for these patients is yet to establish. METHODS: Differential expressed genes (DEGs) between paired normal mucosa, primary GC and OM of patients from Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 6) were identified by transcriptome sequencing, followed by the functional annotation of enriched hallmark pathways of DEGs between them. CIBERSORT was used to profile the relative expression level of 22 immune cell subsets in normal tissues, primary and metastatic tumors, followed by weighted gene coexpression network analysis (WGCNA) uncovering immune cell-correlated gene sets. The intersected genes between DEGs and M2 macrophage-related genes were processed by least absolute shrinkage and selection operator (LASSO) regression analysis to construct a predictive signature, M2GO, which was further validated by training set and test set of The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD), GSE62254 and GSE84437 cohorts. GC patients were divided into M2GO-high and -low subgroup according to the optimal cutoff value of the M2GO score. Furthermore, the clinical, molecular and immune features between M2GO-high and -low subgroups were analyzed. Clinical cohorts of immunotherapy were used to validate the predictive value of M2GO in regard to immunotherapy effectiveness. RESULTS: Transcriptomic sequencing and follow-up analyses of triple-matched normal tissues, primary and ovarian metastatic tumors identified distinctive sets of DEGs and enriched immune-, cancer- and metastasis-related pathways between them. Of note, M2 macrophage, a major immunosuppressive and pro-tumorigenic component within TIME, was significantly up-regulated in OMs. WGCNA and LASSO regression were applied to establish a novel OM- and M2 macrophage-related predictive signature, M2GO, based on M2 macrophage-related prognostic genes including GJA1, MAGED1 and SERPINE1. M2GO served as an independent prognostic factor of GC patients. Comprehensive molecular and immune characterization of M2GO-based subgroups uncovered their distinctive features in terms of enriched functional pathways, tumor mutation burden, key immune checkpoints, major regulators of natural immune cGAS-STING pathway, infiltrated subsets of immune cells and tumor immune exclusion/dysfunction (TIDE) score. Notably, the M2GO score was significantly lower in responsive group than non-responsive group (P < 0.05) in clinical cohort of metastatic GC patients undergoing immunotherapy. CONCLUSION: Transcriptomic characterization of paired normal mucosae, primary and ovarian metastatic tumors revealed their unique molecular and immune features. Follow-up analyses established a novel OM- and M2 macrophage-related signature, M2GO, which served as a promising prognostic and immunotherapeutic biomarker to distinguish the clinical outcome, molecular and immune features of GC patients and predict their differential responses to immunotherapy.

Comprehensive analysis of immune subtypes reveals the prognostic value of cytotoxicity and FAP+ fibroblasts in stomach adenocarcinoma.

BACKGROUND: The heterogeneity limits the effective application of immune checkpoint inhibitors for patients with stomach adenocarcinoma (STAD). Precise immunotyping can help select people who may benefit from immunotherapy and guide postoperative management by describing the characteristics of tumor microenvironment. METHODS: Gene expression profiles and clinical information of patients were collected from ACRG and TCGA-STAD datasets. The immune subtypes (ISs) were identified by consensus clustering analysis. The tumor immune microenvironments (TIME) of each IS were characterized using a series of immunogenomics methods and further confirmed by multiplex immunohistochemistry (mIHC) staining in clinical samples. Two online datasets and one in-house dataset were utilized to construct and validate a prognostic immune-related gene (IRG) signature. RESULTS: STAD patients were stratified into five reproducible ISs. IS1 (immune deserve subtype) had low immune infiltration and the highest degree of HER2 gene mutation. With abundant CD8+ T cells infiltration and activated cytotoxicity reaction, patients in the IS2 (immune-activated subtype) had the best overall survival (OS). IS3 and IS4 subtypes were both in the reactive stroma state and indicated the worst prognosis. However, IS3 (immune-inhibited subtype) was characterized by enrichment of FAP+ fibroblasts and upregulated TGF-ß signaling pathway, while IS4 (activated stroma subtype) was characterized by enrichment of ACTA2+ fibroblasts. In addition, mIHC staining confirmed that TGF-ß upregulated FAP+ fibroblasts were independent risk factor of OS. IS5 (chronic inflammation subtype) displayed moderate immune cells infiltration and had a relatively good survival. Lastly, we developed a nine-IRG signature model with a robust performance on overall survival prognostication. CONCLUSIONS: The immunotyping is indicative for characterize the TIME heterogeneity and the prediction of tumor prognosis for STADs, which may provide valuable stratification for the design of future immunotherapy.

Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPKα/SLC7A11/GPX4 axis in colorectal cancer.

The present study aims to investigate the mechanism of the nature compound gambogenic acid (GNA) on the apoptosis and ferroptosis in colorectal cancer (CRC). The effect of GNA on the proliferation of CRC cell lines were detected by MTT and clonogenic assay. The xenograft tumor model was established, and the inhibition effect of GNA were evaluated by observing the tumor growth. The endoplasmic reticulum (ER) of HCT116 was observed by using the ER tracker. The TargrtScan database was used to predict the miRNA binding sites. The level of miRNA with GNA treatment was explored by real-time quantitative PCR. The effect of ferroptosis were evaluated by detect the expression of reactive oxygen species (ROS), intracellular ferrous iron (Fe2+ ), malondialdehyde (MDA), glutathione (GSH), subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase (GPX)4, transferrin, and ferritin by Western blot. GNA isolated from gamboge can inhibit the growth and proliferation of CRC cell lines in a concentration-dependent manner. GNA activated ER stress by upregulating miR-1291, and miR-1291 targeted the forkhead box protein A2 (FOXA2). GNA also induced ROS production and mediated the Fenton reaction by activating transferrin to increase Fe2+ , thus inducing ferroptosis. In addition, GNA could induce ferroptosis through the depletion of GSH and GPX4. Furthermore, GNA treatment regulated iron metabolism by activating AMPKα/SLC7A11/GPX4 signaling. In conclusion, GNA activated ER stress via miR-1291 and induced ferroptosis in CRC cells and might be a new inducer of ferroptosis, which can expand the efficacy of chemotherapy drugs.

Calcipotriol abrogates cancer-associated fibroblast-derived IL-8-mediated oxaliplatin resistance in gastric cancer cells via blocking PI3K/Akt signaling.

Activation of vitamin D receptor (VDR) in cancer-associated fibroblasts (CAFs) has been implicated in hesitating tumor progression and chemoresistance of several human malignancies. Yet, the role of VDR in CAF-induced chemotherapy resistance of gastric cancer (GC) cells remains elusive. In this study we first conducted immunohistochemistry analysis on tissue microarrays including 88 pairs of GC and normal mucosa samples, and provided clinical evidence that VDR was mainly expressed in gastric mucous cells but almost invisible in CAFs, and VDR expression was negatively correlated with malignant clinical phenotype and advanced stages, low VDR expression confers to poor overall survival rate of patients with GC. In a co-culture system of primary CAFs and cancer cells, we showed that treatment of HGC-27 and AGS GC cells with VDR ligand calcipotriol (Cal, 500 nM) significantly inhibited CAF-induced oxaliplatin resistance. By using RNA-sequencing and Human Cytokine Antibody Array, we demonstrated that IL-8 secretion from CAFs induced oxaliplatin resistance via activating the PI3K/AKT pathway in GC, whereas Cal treatment greatly attenuated the tumor-supportive effect of CAF-derived IL-8 on GC cells. Taken together, this study verifies the specific localization of VDR in GC tissues and demonstrates that activation of VDR abrogates CAF-derived IL-8-mediated oxaliplatin resistance in GC via blocking PI3K/Akt signaling, suggesting vitamin D supplementation as a potential strategy of enhancing the anti-tumor effect of chemotherapy in GC.

The immune subtypes and landscape of sarcomas.

BACKGROUND: Considering the molecular heterogeneity of sarcomas and their immunologically quiet character, immunotherapy (e.g., immune checkpoint inhibitors) plays a viable role in only a subset of these tumors. This study aimed to determine the immune subtypes (IMSs) of sarcomas for selecting suitable patients from an extremely heterogeneous population. RESULTS: By performing consensus clustering analysis of the gene expression profiles of 538 patients with sarcomas in online databases, we stratified sarcomas into three IMSs characterized by different immune cell features, tumor mutational burdens (TMBs), gene mutations, and clinical outcomes. IMS1 showed an immune "hot" and immunosuppressive phenotype, the highest frequencies of CSMD3 mutation but the lowest frequencies of HMCN1 and LAMA2 mutations; these patients had the worst progression-free survival (PFS). IMS2 was defined by a high TMB and more gene mutations, but had the lowest frequency of MND1 mutations. IMS3 displayed the highest MDN1 expression level and an immune "cold" phenotype, these patients had the worst PFS. Each subtype was associated with different expression levels of immunogenic cell death modulators and immune checkpoints. Moreover, we applied graph learning-based dimensionality reduction to the immune landscape and identified significant intra-cluster heterogeneity within each IMS. Finally, we developed and validated an immune gene signature with good prognostic performance. CONCLUSIONS: Our results provide a conceptual framework for understanding the immunological heterogeneity of sarcomas. The identification of immune-related subtypes may facilitate optimal selection of sarcoma patients who will respond to appropriate therapeutic strategies.

Multiplexed immunofluorescence analysis of CAF-markers, EZH2 and FOXM1 in gastric tissue: associations with clinicopathological parameters and clinical outcomes.

BACKGROUND: The aim of this study is to explore the expression and clinical relevance of CAF-associated markers, EZH2 and FOXM1 in gastric samples. METHODS: Protein expression were detected and evaluated by multi-plex immunofluorescence (mIF) in 93 cases of gastric cancer (GC) and 31 cases of gastric intraepithelial neoplasia (GIN). The correlation among their expression, and the relationship of them with clinicopathological parameters and prognosis in GC were then analyzed. RESULTS: FAP was specific expressed in the CAFs of GC samples, and thus be utilized as a CAF-associated marker in our subsequently analysis. The immunostaining of EZH2, FOXM1 and FAP were significantly upregulated in patients with GC tissues than in those normal gastric mucosa or GIN tissues. The average fluorescence intensity of FAP was slightly positively correlated with EZH2 in GC, GIN and normal samples, whereas the percentage of FAP positive cells has no correlation with that of EZH2. Both the percentage of positive cells and the average fluorescence intensity of FOXM1 were positively correlated with that of FAP and EZH2 in GC, GIN and normal samples, except for FOXM1 and EZH2 expression in normal tissue samples. No significant association was observed between FAP expression and any clinicopathological parameters, whereas the positive frequency of EZH2 and FOXM1 were correlated with tumor location significantly and tumor invasion depth, respectively. In addition, there was strong positive correlations between FAP protein expression and overall survival (OS) and disease-free survival (DFS), and EZH2 expression was positively associated with OS in patients with GC. Furthermore, EZH2 and FAP protein expression was an independent prognostic factor for OS and DFS, respectively. CONCLUSIONS: These results suggest that both EZH2 and FOXM1 expression was positively associated with CAFs abundance in GC. They may be potential cellular target for therapeutic intervention, especially in patients with a large number of CAFs.

Molecular signatures of tumor progression in pancreatic adenocarcinoma identified by energy metabolism characteristics.

BACKGROUND: In this study, we performed a molecular evaluation of primary pancreatic adenocarcinoma (PAAD) based on the comprehensive analysis of energy metabolism-related gene (EMRG) expression profiles. METHODS: Molecular subtypes were identified by nonnegative matrix clustering of 565 EMRGs. An overall survival (OS) predictive gene signature was developed and internally and externally validated based on three online PAAD datasets. Hub genes were identified in molecular subtypes by weighted gene correlation network analysis (WGCNA) coexpression algorithm analysis and considered as prognostic genes. LASSO cox regression was conducted to establish a robust prognostic gene model, a four-gene signature, which performed better in survival prediction than four previously reported models. In addition, a novel nomogram constructed by combining clinical features and the 4-gene signature showed high-confidence clinical utility. According to gene set enrichment analysis (GSEA), gene sets related to the high-risk group participate in the neuroactive ligand receptor interaction pathway. CONCLUSIONS: In summary, EMRG-based molecular subtypes and prognostic gene models may provide a novel research direction for patient stratification and trials of targeted therapies.

Stanniocalcin-2 promotes cell EMT and glycolysis via activating ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma.

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.

DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation.

Long noncoding RNAs (lncRNAs) are involved in a variety of cancers, but the role of LncRNA DUBR in lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, remains unclear. In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD. Analysis of mRNA expression in The Cancer Genome Atlas (TCGA) LUAD database and in-house LUAD cohort (n = 94) showed that DUBR was significantly downregulated in LUAD, and was associated with poor prognosis. In LUAD cell lines (H1975, A549), overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells. We demonstrated that c-Myc could bind to the promoter of DUBR, and transcriptionally suppressed its expression. Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells, whereas knockdown of DUBR partially rescued c-Myc-knockdown suppressed cell migration and invasion. Furthermore, DUBR overexpression significantly increased the expression of a downstream protein of DUBR, zinc finger, and BTB domain containing 11 (ZBTB11), in H1975 and A549 cells; knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion; knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells. Finally, we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells. In short, we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation, which provides new insights into the regulatory mechanism of DUBR.

Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating ß-catenin/SIX1 signaling pathway in gastric cancer.

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the ß-catenin expression level through the AKT1/GSK3ß signaling pathway. Meanwhile, the binding sites of ß-catenin were identified in the promoter region of SIX1 and it was also demonstrated that ß-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/ß-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.

Identification of lipid metabolism-related genes as prognostic indicators in papillary thyroid cancer.

Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancers. In this study, we investigated the prognostic value of lipid metabolism-related genes in papillary thyroid cancer (PTC). The recurrence predictive gene signature was developed and internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO, and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry of tissue microarray using in-house cohorts, which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram, and decision curve analyses were used to assess the performance of the gene signature. We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a four-gene signature recurrence risk model. The expression profiles of the four genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibit notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicate the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. Single-sample gene set enrichment analysis showed that high-risk cases exhibit changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signaling pathways. Our results indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients.

Primary appendiceal mucinous neoplasm: Gynecological manifestations, management, and prognosis.

OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristics, management, and survival of patients with appendiceal mucinous neoplasm misdiagnosed as ovarian tumor and initially treated by a gynecological oncologists. METHODS: We retrospectively reviewed data for 71 patients identified from January 1, 2006 to September 31, 2018 with a final pathological diagnosis of appendiceal mucinous neoplasm. All patients were diagnosed as having ovarian tumor preoperatively and initially treated at Department of Gynecological Oncology. RESULTS: The median patients' age was 61 years, and the median peritoneal cancer index (PCI) was 16, with a complete cytoreduction score (CCR0/1) achieved in 46.47% of patients. Two patients received hyperthermic intraperitoneal chemotherapy (HIPEC). Estimated 5-year and 10-year survival was 76.7% and 53.4%, respectively. PCI and lactate dehydrogenase (LDH) levels were identified as independent predictors of poor overall survival. CONCLUSIONS: Because of the high rate of ovarian metastases and the difficulty diagnosing appendiceal mucinous neoplasm preoperatively, this condition should be highlighted in gynecological oncology. Because initial surgical intervention is often performed by gynecological oncologists, updating the management guidelines for appendiceal mucinous tumor is needed because the rates of CCR0/1 resection and HIPEC are much lower in patients who are misdiagnosed.

Prognostic and Predictive Value of Blood Tumor Mutational Burden in Patients With Lung Cancer Treated With Docetaxel.

BACKGROUND: Biomarkers for chemotherapy efficacy in non-small cell lung cancer (NSCLC) are lacking. This retrospective study assesses the association between blood-based tumor mutational burden (bTMB) and clinical benefit of chemotherapy. METHODS: Clinical and targeted next-generation sequencing data from the OAK trial (training set; n=318) and POPLAR trial (validation set; n=106) in the docetaxel arm were analyzed. The cutoff value of bTMB for outcome prediction was determined based on a time-dependent receiver operating characteristic curve in the training set, and propensity score matching (PSM) was conducted. The primary outcome was overall survival (OS). Durable clinical benefit (DCB) was defined as OS lasting >12 months. Interaction between treatment and bTMB was assessed in the combined set. RESULTS: A lower bTMB was observed in patients with DCB compared with no durable benefit, and in those with a partial response and stable disease compared with progressive disease. The optimized cutoff value of bTMB for predicting OS was 7 single-nucleotide variants per megabase. In the training set, a low bTMB was significantly associated with longer OS and progression-free survival (PFS). The prognostic value of bTMB was confirmed in the validation set and PSM set. The interaction between bTMB and treatment was significant for PFS (interaction P=.043) in the combined set. Mutations in KEAP1 were associated with high bTMB and a lack of benefit from chemotherapy. CONCLUSIONS: Low bTMB is associated with a survival advantage in patients with NSCLC treated with docetaxel, suggesting the prognostic and predictive potential of bTMB for determining chemotherapy efficacy.

DEPDC1B knockdown inhibits the development of malignant melanoma through suppressing cell proliferation and inducing cell apoptosis.

Malignant melanoma (MM) remains the leading cause of skin cancer related death, which has very poor prognosis because of locoregional recurrence and distant metastasis. DEPDC1B (DEP domain-containing protein 1B), has been proved to be associated with some types of malignant tumors. However, the role of DEPDC1B in MM is still unknown. In this study, the expression levels of DEPDC1B in MM tissues were detected by IHC. DEPDC1B knockdown cell lines were constructed, evaluated by Western blot and qRT-PCR, and also used for construction of mice xenograft models. Cell proliferation and apoptosis were investigated by MTT, colony formation assay and flow cytometry, respectively. The results indicated significantly up-regulated expression of DEPDC1B in tumor tissues. Moreover, knockdown of DEPDC1B could inhibit cell proliferation while inducing cell apoptosis. The in vivo study demonstrated the significant suppression of tumor growth by knockdown of DEPDC1B. Finally, the results of antibody array proved the up-regulation of pro-apoptotic proteins and the down-regulation of anti-apoptotic proteins by DEPDC1B knockdown. Therefore, it could be concluded that DEPDC1B was involved in the development and progression of MM, which may act as promotor for MM and could be a potential therapeutic target.

Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity.

BACKGROUND AND AIM: Amphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. This study characterized the clinicopathologic and survival analysis of this tumor, further compared the genetic diversities among amphicrine carcinoma and other tumors. MATERIALS AND METHODS: The clinicopathologic characteristics and survival outcomes of amphicrine carcinoma in this study were analyzed. The pan-cancer transcriptome assay was utilized to compare the genetic expression profile of this entity with that of conventional adenocarcinoma or neuroendocrine tumors. RESULTS: Ten cases (all in male patients) were identified in the stomach or intestine, with a median patient age of 62 years. There were characteristic patterns in the tumors: tubular, fusion or single-file growth of goblet- or signet ring-like cells. Four tumors were classified as low-grade and 6 as high-grade according to the histologic architecture. All cases were positive for neuroendocrine markers (synaptophysin and chromogranin A) and showed intracellular mucin in the amphicrine components. Four cases exhibited mRNA expression patterns showing transcriptional homogeneity with conventional adenocarcinomas and genetic diversity from neuroendocrine tumors. During the follow-up period, 3 patients died of disease, all of whom had high-grade tumors. Patients with high-grade amphicrine carcinoma had worse outcomes than those with low-grade tumors. CONCLUSIONS: This study confirms the morphological, immunostaining and transcriptome alterations in amphicrine carcinoma distinct from those in conventional adenocarcinomas and neuroendocrine tumors, but additional studies are warranted to determine the biological behavior and therapeutic response.

Magnetic Resonance Imaging Features of Breast Encapsulated Papillary Carcinoma.

OBJECTIVE: This study aimed to describe the magnetic resonance imaging (MRI) features of pure breast encapsulated papillary carcinoma (EPC). MATERIALS AND METHODS: Ten patients with histopathologically confirmed breast pure EPC were reviewed. Two radiologists evaluated lesion MRI characteristics. RESULTS: The EPC presented oval or round mass with circumscribed margin on MRI. In addition, 4 cases exhibited a cystic-solid mixed mass with mural nodules, and 4 cases exhibited a liquid level that indicated the possibility of hemorrhage. CONCLUSIONS: A well-defined cystic-solid mixed mass with mural nodules, or a circumscribed mass exhibiting the possibility of hemorrhage, may suggest the diagnosis of EPC.

PTTG3P promotes gastric tumour cell proliferation and invasion and is an indicator of poor prognosis.

Pseudogenes play a crucial role in cancer progression. However, the role of pituitary tumour-transforming 3, pseudogene (PTTG3P) in gastric cancer (GC) remains unknown. Here, we showed that PTTG3P expression was abnormally up-regulated in GC tissues compared with that in normal tissues both in our 198 cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database. High PTTG3P expression was correlated with increased tumour size and enhanced tumour invasiveness and served as an independent negative prognostic predictor. Moreover, up-regulation of PTTG3P in GC cells stimulated cell proliferation, migration and invasion both in vitro in cell experiments and in vivo in nude mouse models, and the pseudogene functioned independently of its parent genes. Overall, these results reveal that PTTG3P is a novel prognostic biomarker with independent oncogenic functions in GC.