Single-cell landscape of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.

Establishment of a staging system for visceral sarcoma.

BACKGROUND: Visceral sarcoma is a rare malignancy with a poor prognosis. However, there is no recommended prognostic staging system for the malignant disease. METHOD: We analyzed the data of patients diagnosed with primary soft tissue sarcoma (STS) of the abdomen and thoracic visceral organs between 2006 and 2017 at our hospital. Prognostic factors (size, tumor grade, and lymph node metastasis) were analyzed in our cohort (n = 203) and the SEER validation cohort (n = 5826). RESULTS: Tumor size, grade, and lymph node metastasis were important prognostic factors for visceral sarcoma in both our and the SEER cohorts. Based on these prognostic factors, we established a new staging system for visceral sarcoma, by which patients could be stratified into clinically meaningful and non-overlapping stages in both our cohort and the SEER validation series. Moreover, the area under the curve (AUC) value of the staging system for 5-year survival was 0.84 (95% CI: 0.78-0.89) in our series and 0.80 (95% CI: 0.79-0.81) in SEER series, respectively. In addition, compared with the widely used FIGO staging system for female genital sarcoma, the visceral sarcoma staging system could more effectively and reliably stratify patients into four different prognostic groups. CONCLUSIONS: The visceral sarcoma staging system is applicable for STS of the abdomen and thoracic visceral organs and is better than the current FIGO staging system for female genital sarcoma and should be incorporated into the AJCC Cancer Staging Manual.

The preoperative value of fine-needle aspiration in adult soft tissue lesions: An analysis of 514 cases at Shanghai Cancer Center.

BACKGROUND: Fine-needle aspiration (FNA) cytology is a rapid, inexpensive, and uncomplicated method. However, its role in the assessment of soft tissue lesions (STL) remains controversial, and its ability to guide surgical treatment remains unclear. This study investigated the positive predictive value (PPV) of FNA for detecting malignancy and its guiding role in the surgical treatment of STL. METHODS: We retrospectively reviewed 514 patients with STL who underwent preoperative FNA and surgical resection between March 2015 and August 2021. Imaging assessments confirmed that radical surgery was possible. The FNA results were compared with the final postoperative histopathology. RESULTS: Of the 514 patients with STL, 496 (mean age, 48.9 years; range, 21-91 years) were eligible for analysis, the male to female ratio was 111:100. According to the 496 FNA results, 90 (18.2%) were positive for malignancy, 84 (16.9%) were suspicious for malignancy, 80 (16.1%) were spindle cell present, and 242 (48.8%) were negative for malignant cells. Compared with postoperative histopathology, FNA correctly detected all 90 malignant lesions and 203 of the 242 benign lesions. A total of 39 false-negative results were obtained. FNA showed an accuracy of 88.3%, sensitivity of 69.8%, specificity of 100%, negative predictive value (NPV) of 83.9%, and PPV of 100%. In the other seven validation cohorts (n = 1157), FNA had a consistently high PPV, with values all more than 93%. CONCLUSION: Our results demonstrate that FNA has a high PPV for detecting malignancy. For patients with resectable lesions and malignant FNA, the core needle biopsy (CNB) step can be omitted with multidisciplinary evaluation, and subsequent radical surgery can be performed.

Oncogenic alterations reveal key strategies for precision oncology in melanoma treatment.

Background: Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid tumors, including melanomas, to identify potential drug targets. However, the association between clinical outcomes and the molecular alterations has not yet been fully clarified. Methods: A total of 108 patients with melanoma were included in this study, 95 of whom had both sequencing data and clinical outcomes were collected. We analyzed the genetic alterations of 108 malignant melanoma patients using the OncoCare panel, which covers 559 genes. Results: A model was also established to predict side effects through a combination analysis of clinical data and somatic variants, yielding an area under the receiver operating characteristic curve (AUROC) score of 0.8. We also identified epidermal growth factor receptor (EGFR) mutation was excellent predictor for progression-free survival (PFS) for patient who received immunotherapy (log-rank P=0.01), while tumor mutation burden (TMB) was found to not be significantly associated with PFS (log-rank P=0.87). Combining clinical features with genetic analysis, we found that patients carrying both DNA POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate. Conclusions: Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.

Genomic Analyses of Metaplastic or Sarcomatoid Carcinomas From Different Organs Revealed Frequent Mutations in KMT2D.

Background: Metaplastic or sarcomatoid carcinomas (MSCs) are rare epithelial malignancies with heterologous histological differentiation that can occur in different organs. The objective of the current study was to identify novel somatically mutated genes in MSCs from different organs. Methods: Whole-exome sequencing was performed in 16 paired MSCs originating from the breast (n = 10), esophagus (n = 3), lung (n = 2), and kidney (n = 1). In addition, we collected data on KMT2D mutations from eight independent cohorts (n = 195) diagnosed with MSCs derived from the breast (n = 83), liver (n = 8), esophagus (n = 15), lung (n = 10), and uterus or ovary (n = 79). The expression of KMT2D and its clinical significance were evaluated in our cohort. Results: The most frequently mutated genes were TP53 (13/16, 81%) and KMT2D (5/16,31%). We identified seven somatic KMT2D mutations in the exploratory cohort (n = 16 tumors), including three nonsense mutations, two frameshift indels, one missense mutation, and one splice site mutation. Interestingly, two patients showed double hits on KMT2D with nonsense mutations and frameshift indels. In the eight validation cohorts (n = 195), the average mutation rates for TP53 and KMT2D were 78% (152/195) and 13% (25/195), respectively. Two or more hits on KMT2D were also present in three validation cohorts. Furthermore, KMT2D mutations were associated with low expression of KMT2D, large tumor size and unfavorable prognosis. Conclusions: These findings provide clues for understanding the genetic basis of MSCs originating from different organs and implicate KMT2D alteration as a frequent pathogenic mutation, allowing provision of appropriate treatment for this rare malignant disease in the future.

Chondroitin polymerizing factor (CHPF) promotes development of malignant melanoma through regulation of CDK1.

Chondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.

Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution.

PURPOSE: Our study aimed to describe the clinical features of undifferentiated pleomorphic sarcoma (UPS) and identify the predictors of poor outcomes. PATIENTS AND METHODS: The clinicopathological variables and treatment strategies of 100 UPS patients who underwent surgical resections at a single institution between November 2004 and July 2016 were reviewed. Kaplan-Meier and Cox regression method were conducted for survival analysis. RESULTS: The median follow-up time was 94 months (range, 1.5-154 months). R0 resection was applied for 72 cases, and the median tumor size was 5.75cm (range, 1-30cm). Tumor grades of 45 patients were intermediate grade (G2), and 54 patients were with advanced stage (stage III/IV). Twenty-seven patients presented with tumors involving important structures, in which the nerve was the most frequently invaded structure (n=12). During the follow-up, 40 patients suffered from postoperative local recurrence, and distant metastasis was observed in 25 patients which mainly metastasized to the lung (n=14). The 5-year OS rate, 5-year LRFS rate, and 5-year MFS rate was 53%, 55%, and 70%, respectively. Multivariate analysis revealed that tumor presentation, tumor size, and important structures involved (p=0.033, p=0.004, and p=0.033, respectively) were independent prognostic factors associated with OS. Meanwhile, age, resection quality and tumor grade were independent prognostic factors for LRFS (p=0.033, p=0.045, and p=0.007, respectively) and tumor depth was significantly associated with MFS (p=0.050) in multivariate analysis. CONCLUSION: Primary treatment of UPS should be conducted by experts in large sarcoma center. Wide surgical margin provides sufficient control of the disease recurrence.

Changes in the tumor immune microenvironment in resected recurrent soft tissue sarcomas.

BACKGROUND: Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). METHODS: We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. RESULTS: We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. CONCLUSIONS: The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Common Nevus and Skin Cutaneous Melanoma: Prognostic Genes Identified by Gene Co-Expression Network Analysis.

Skin cutaneous melanoma (SCM) is a common malignant tumor of the skin and its pathogenesis still needs to be studied. In this work, we constructed a co-expression network and screened for hub genes by weighted gene co-expression network analysis (WGCNA) using the GSE98394 dataset. The relationship between the mRNA expression of hub genes and the prognosis of patients with melanoma was validated by Gene Expression Profiling Interactive Analysis (GEPIA) database. Furthermore, immunohistochemistry in the Human Protein Atlas was used to validate hub genes and grayscale analysis was performed using ImageJ software. It was found that the yellow module was most significantly associated with the difference between common nevus and SCM, and 13 genes whose expression correlation >0.9 were candidate hub genes. The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of SCM. STK26 (P = 0.0024) and KCNT2 (P < 0.0001) were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future.

Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing.

BACKGROUND/AIM: Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm characterized by chromosomal instability. The aim of this study was to identify fusion events involved in UPS. MATERIALS AND METHODS: Transcriptome sequencing was performed to search for new fusion genes in 19 UPS samples, including two paired recurrent (R) and re-recurrent (RR) samples. RESULTS: A total of 66 fusion genes were detected. Among them, 10 novel fusion genes were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing. Retinoblastoma (RB1) fusions (2 cases) were the most recurrent fusion genes. The gene fusions RB1-RNASEH2B, RB1-FGF14-AS1, and E2F6-FKBP4 were correlated with the Rb/E2F pathway. Pseudogenes were involved in the formation of the gene fusions CIC-DUX4L8 and EIF2AK4-ANXA2P2. Importantly, targetable gene fusions (PDGFRA-MACROD2 and NCOR1-MAP2K1) were detected in UPS. CONCLUSION: Screening for the presence of fusion transcripts will provide vital clues to the understanding of genetic alterations and the finding of new targeted therapies for UPS.

Prognostic analysis of surgically treated clear cell sarcoma: an analysis of a rare tumor from a single center.

BACKGROUND: The objective of this retrospective study was to evaluate the prognostic value of various factors in clear cell sarcoma patients after radical surgery. METHODS: Forty-two clear cell sarcoma patients from August 2006 to March 2018 were included in the study. Curves of disease-free survival and overall survival were calculated using the Kaplan-Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. Laboratory test of peripheral blood was recorded before surgery. The optimal cutoff value of systemic inflammatory markers was defined by receiver-operating curve analysis. RESULTS: The 5-year DFS and 5-year OS rate were 22% and 46%, respectively. The median DFS and OS times were 12 and 41.5 months, respectively. In univariate analysis, there was a significant association between shorter DFS and tumor size larger than 5 cm (p = 0.0043), positive surgical margin (p = 0.0233), and the neutrophil-to-lymphocyte ratio (NLR) higher than 2.73 (p = 0.0009). Furthermore, we observed a significant association between shorter OS and tumor size larger than 5 cm (p = 0.0075), positive surgical margin (p = 0.0101), NLR higher than 2.73 (p = 0.0126), the platelet-to-lymphocyte ratio (PLR) higher than 103.89 (p = 0.0147) and the lymphocyte-to-monocyte ratio (LMR) lower than 4.2 (p = 0.0445). A multivariate analysis demonstrated that the surgical margin (p = 0.013) and NLR (p = 0.001) were significantly associated with DFS. Tumor size (p = 0.010) and NLR (p = 0.013) were independent prognostic factors for OS. CONCLUSIONS: This study had the second largest sample around the world and preoperative NLR may be a useful prognostic factor in CCS patients after radical surgery.

Pathogenic and Targetable Genetic Alterations in Resected Recurrent Undifferentiated Pleomorphic Sarcomas Identified by Targeted Next-generation Sequencing.

BACKGROUND/AIM: Undifferentiated pleomorphic sarcomas (UPSs) are difficult to treat, with a high recurrence rate. However, the genetic and molecular characterization of recurrent UPS has not been identified. PATIENTS AND METHODS: In this study, we investigated the pathogenic and targetable genetic alterations in 16 paired locally pre-recurrent and post-recurrent UPS cases by targeted next-generation sequencing (466 genes). RESULTS: Sequence variations were most frequently found in TP53 (66%), ATRX (34%), and RB1 (28%). In addition, for the first time, recurrent IL7R gene amplification (19%) and KMT2C gene mutation (16%) were detected in UPS. Interestingly, genetic alterations varied with tumor relapse. Importantly, targetable driver variants were found in recurrent UPS. Mutated genes were correlated with the cell cycle, PI3K/mTOR and RAS/MAPK signaling pathways. TMB was also found to be increased after tumor recurrence (4.6 vs. 7.5 mutations/MB, p=0.0343). CONCLUSION: Routine use of targeted next-generation sequencing for recurrent UPS can facilitate timely therapeutic decision-making.

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.

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications.

BACKGROUND: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. METHODS: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information's Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As2O3 treatment. RESULTS: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. CONCLUSIONS: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As2O3) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

Expression of PD-L1 in mononuclear cells, multinucleated cells, and foam cells in tenosynovial giant cell tumors.

Tenosynovial giant cell tumor (TGCT) is a rare, proliferative and inflammatory disease with activation of colony stimulating factor 1 (CSF1) expression, and exhibits abnormal proliferation of mononuclear cells, multinucleated cells and foam cells. PD-L1 inhibitors represent a promising strategy in a variety of tumors. However, PD-L1 expression has never been studied in CSF1 activated TGCT. In this study, we determined the expression of programmed cell death ligand 1 (PD-L1) in 40 TGCT cases by immunohistochemistry and evaluated its clinical significance. We found that PD-L1 was positively expressed in 52.5% of all patients, and among them, the mononuclear cells, multinucleated cells, and foam cells with positive PD-L1 expression were observed in 21 (52.5%), 10 (25.0%), and 7 (17.5%) patients, respectively. The mononuclear cells and foam cells exhibited PD-L1 expression on the membrane or in the cytoplasm, and the multinucleated cells showed membranous PD-L1 expression. In addition, the PD-L1-positive mononuclear cells, multinucleated cells, and foam cells co-expressed CD68. Moreover, the patients with positive PD-L1 expression had a larger tumor size than those with negative PD-L1 expression. We further found that the foam cells of human coronary atherosclerosis also exhibited the expression of PD-L1 in two of three patients. These findings provide valuable evidence that PD-L1 is highly positive in CSF1-activated TGCT, and treatment with anti-PD-L1 agents may be a valuable therapeutic option for those diseases with PD-L1 expression on mononuclear cells, multinucleated cells, or foam cells.

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway.

BACKGROUND/AIMS: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. METHODS: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. RESULTS: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. CONCLUSION: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

Reconstruction of extensive thoracic wall defect using the external oblique myocutaneous flap: An analysis on 20 Chinese patients with locally advanced soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas are rare neoplasms that can occur in the thoracic wall, abdominal wall, extremities, and inguinal region. Wide local resection, with precise histological margin control, results in large skin defects that are challenging to close. Various repair procedures, such as vertical rectus abdominis flaps (VRAM), latissimus dorsi flaps, and tensor fascia lata (TFL) flaps are used to cover broad thoracic wall defects. Although the cosmetic reconstruction results of using these flaps are often excellent, each has significant drawbacks. The external oblique musculocutaneous flap is a simple and safe surgical procedure for covering thoracic wall defects. OBJECTIVE: This study aimed to retrospectively assess the safety and technique of using the external oblique musculocutaneous flap to cover large thoracic wall defects after radical excision of locally advanced sarcomas in 20 patients at a single institution. METHOD: From January 2006 to December 2016, 20 Chinese patients with large advanced sarcomas on their trunks received wide local resection, with precise histological negative margins. The external oblique musculocutaneous flap, mobilized from the ipsilateral abdominal wall, was harvested to cover broad thoracic wall defects. RESULTS: Among the 20 sarcoma patients (12 females and 8 males, ranging in age from 25 to 73 years), there were five patients with primary tumors and 15 patients with recurrent tumors. The median tumor diameter was approximately 15.3 cm. After excising the lesion, the median time to cover the defect with the external oblique myocutaneous flap was 66 min. The average blood loss when harvesting the flap was approximately 48 mL. For the 20 patients in our cohort, the external oblique flap achieved closure of defects measuring an average area of 256 cm2 . No other flaps or reconstruction techniques were used to cover the large defects in this study. There were no deaths directly related to the flap reconstruction procedures. CONCLUSION: The external oblique musculocutaneous flap was a safe and reliable method of covering broad thoracic wall defects after radical tumor excision.

Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer.

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC.