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Background Liver cancer (LC) is one of the most fatal cancers throughout the world. More efficient and sensitive gene signatures that could accurately predict survival in LC patients are vitally needed to promote a better individualized and effective treatment. Material/methods 422 LC and adjacent normal tissues with both RNA-Seq and clinical data in TCGA were embedded in our study. Gene set enrichment analysis (GSEA) was applied to identify genes and hallmark gene sets that are more valuable for liver cancer therapy. Cox regression analysis was used to identify genes related to overall survival (OS) and build the prediction model. cBioPortal database was used to examine the alterations of the panel mRNA signature. ROC curves and Kaplan–Meier curves were used to validate the prediction model. Besides, the expression of the genes in the model were validated using quantitative real-time PCR in clinical tissue specimens. Results The panel of DNA repair-related mRNA signature consisted of seven mRNAs: RFC4 (replication factor C subunit 4), ZWINT (ZW10 interacting kinetochore protein), UPF3B (UPF3B regulator of nonsense mediated mRNA decay), NCBP2 (nuclear cap binding protein subunit 2), ADA (adenosine deaminase), SF3A3 (splicing factor 3a subunit 3) and GTF2H1 (general transcription factor IIH subunit 1). On-line analysis of cBioPortal database found that the expression of the panel mRNA has a wide variation ranging from 7 to 10%. All the mRNAs were significantly upregulated in LC tissues compared to normal tissues (P P-value Conclusions Our study demonstrated a mRNA signature including seven mRNA for prognosis prediction of LC. This panel gene signature provides a new criterion for accurate diagnosis and therapeutic target of LC.

The early diagnosis of lung squamous cell carcinoma (LUSC) is difficult, causing an unsatisfactory prognosis. Therefore, the 5-year survival rate of LUSC is poor. This study aimed at screening the potential diagnostic and prognostic markers for LUSC. The data of LUSC gene expression profiles and DNA methylation were obtained from The Cancer Genome Atlas (TCGA) database; the differentially expressed genes (DEGs) and the differentially methylated genes (DMGs) were screened out by an independent t-test and Benjamini/Hochberg methods. Further, the classifiers of the gene expression and DNA methylation markers in LUSC were constructed. After that, diagnostic and prognostic markers in LUSC were analyzed by the protein-protein interaction (PPI) network. The DEGs and the DMGs from TCGA database of LUSC were screened out. After strict filtration, we identified three potential DMGs (POU domain, class 4, transcription factor 2 [POU4F2], EN1, single-minded homolog 1 [SIM1]) for early diagnosis and seven potential DEGs (G-protein coupled receptor 78 [GPR78], PCDHA5, myosin binding protein H [MYBPH], RTL3, KIAA0408, HSD3B2, PCDHA12) for prognosis of LUSC. The tumor-normal tissue classification model and prognosis model were validated in two independent datasets. In addition, the PPI network was constructed, including three DMGs and the five DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) of the seven DEGs. The potential DMGs (POU4F2, EN1, SIM1) and DEGs (GPR78, MYBPH, KIAA0408, HSD3B2, PCDHA12) for the diagnosis and prognosis of LUSC identified in this article are expected to be further applied in clinical practice of the treatment of LUSC.

Neurologic immune-related adverse events (nirAEs) are uncommon but potentially lethal complications of immune checkpoint inhibitor (ICI) treatment. However, the incidence, radiographic features and prognostic significance of brain magnetic resonance imaging (MRI) changes after ICI treatment remain largely unknown. Consecutive patients with advanced non-small cell lung cancer (NSCLC) at three participating institutions receiving anti-PD-1/PD-L1 therapy from June 2017 to September 2020 were screened, and those who received brain MRI within 6 weeks before ICI initiation and at least one follow-up brain MRI after ICI treatment were included. Serial brain MRI images were independently reviewed by two experienced radiologists. With a median follow-up of 13.2 months, 27 (20.0%) of the 135 enrolled patients developed certain kind of brain MRI aberration. The 1-, 2- and 3-year cumulative incidence of brain MRI aberration was 17.1%, 36.3% and 52.2%, respectively. Brain MRI aberration indicative of stroke, mimicking typical white matter lesions and presenting as T2-hyperintensity suggestive of CNS vasculitis or encephalitis, was documented in 11, 9 and 4 patients, respectively. Patients with brain MRI aberration had higher clinical benefit rate (p = 0.030), longer progression-free survival (p = 0.015) and a tendency of improved overall survival (p = 0.054). Brain MRI aberrations developed after ICI treatment are not uncommon, and their manifestations vary a lot. Patients developing brain MRI aberrations tended to have better prognosis, which needed to be further investigated.

Background Chemoresistance is the major cause of neoadjuvant treatment failure in breast cancer patients. Despite recent progress, the mechanism underlying chemoresistance remains to be further defined. Methods Expression of G protein-coupled receptor 120 (GPR120) was analyzed by immunohistochemistry in the biopsies of primary breast cancer who subsequently underwent preoperative neoadjuvant chemotherapy. In vitro and in vivo loss- and gain-of -function studies were performed to reveal the effects and related mechanism of GPR120 signaling pathway in the chemoresistance of breast cancer cells. Findings We identified that GPR120, a receptor for long-chain fatty acids, was important for the acquisition of chemoresistance in breast cancer cells. We showed that GPR120 expression was positively associated with clinical response to neoadjuvant chemotherapy in patients. In breast cancer cells, GPR120 enhanced the de novo synthesis of fatty acids that served as GPR120 ligands to activate GPR120 signaling via a feedback mechanism. Upregulated GPR120 signaling rendered cells resistant to epirubicin-induced cell death by upregulating ABC transporters expression and thus decreasing the intracellular accumulation of epirubicin. Akt/NF-κB pathway was responsible for the GPR120-mediated expression of ABC transporters leading to modulation of the concentration of chemotherapeutic drugs in cells. The functional importance of GPR120 in chemoresistance was further validated using epirubicin-treated tumor xenografts, in which we showed that blockade of GPR120 signaling with AH7614 or GPR120-siRNA significantly compromised chemoresistance. Interpretation Our results highlight that GPR120 might be a promising therapeutic target for breast cancer chemoresistance. Fund National Natural Science Foundation of China, Ministry of Science and Technology of China, Program of Science and Technology Commission of Shanghai Municipality.

Myocyte enhancer factor 2D (MEF2D) is involved in many aspects of cancer progression, including cell proliferation, invasion, and migration. However, little is known about the role of MEF2D in tumor angiogenesis. Using clinical specimens, colorectal cancer (CRC) cell lines and a mouse model in the present study, we found that MEF2D expression was positively correlated with CD31-positive microvascular density in CRC tissues. MEF2D promoted tumor angiogenesis in vitro and in vivo and induced the expression of proangiogenic cytokines in CRC cells. MEF2D was found to be a downstream effector of hypoxia-inducible factor (HIF)-1α in the induction of tumor angiogenesis. HIF-1α transactivates MEF2D expression by binding to the MEF2D gene promoter. These results demonstrate that the HIF-1α/MEF2D axis can serve as a therapeutic target for the treatment of CRC.

Background Evidence suggests that fatty acid receptor FFAR4 plays a tumor-promoting role in adipose tissue-adjacent malignancies, but its clinical relevance remains unexplored. Here, we investigated the clinical significance and underlying mechanisms of FFAR4 in hormone receptor-positive breast cancer (HRPBC). Methods FFAR4 expression was assessed by immunohistochemistry in an exploration cohort of 307 breast cancer cases collected from two independent institutes. Two public breast cancer microarray datasets served as validation cohorts. Gas chromatography-mass spectrometry was employed to identify FFAR4 ligands in normal and cancerous breast tissues. Survival analyses were performed in all cohorts and designated molecular subgroups. Mechanistic studies were performed in vitro in hormone receptor-positive breast cancer cell lines MCF-7 and T-47D. Results Aberrant FFAR4 expression and endogenous FFAR4 ligands were identified in breast cancer tissues, five FFAR4 ligands showed significantly elevated proportions in cancerous versus normal tissues. In the exploration cohort, FFAR4 was demonstrated as an independent prognostic factor for recurrences (HR: 2.183, 95% CI: 1.360–3.504, P = 0.001) and breast cancer-specific deaths (HR: 2.102, 95% CI: 1.173–3.766, P = 0.013) in HRPBC cases. In contrast, FFAR4 expression was not associated with prognosis in hormone receptor-negative cases. In the validation cohorts, FFAR4 mRNA levels were also observed to be associated with disease recurrence in estrogen receptor-positive cases, but not so in estrogen receptor-negative cases. FFAR4 activation by endogenous ligands and a synthetic ligand TUG891 significantly dampened tamoxifen’s efficacy on HRPBC cells, whereas FFAR4 knockdown or antagonist AH7614 abrogated this effect. Furthermore, FFAR4-induced tamoxifen resistance was dependent on ERK and AKT pathways in HRPBC. Conclusions Our results establish a novel role of FFAR4 and its ligands in the complicated interactions between tissue lipid profile and cancer biology. FFAR4 signaling confers tamoxifen resistance in HRPBC cell line and FFAR4 expression can serve as a prognostic biomarker for tamoxifen-treated HRPBC patients. FFAR4 may serve as a potential target for anti-breast cancer therapies, especially in endocrine resistant cases. Electronic supplementary material The online version of this article (10.1186/s13046-019-1040-3) contains supplementary material, which is available to authorized users.

Background Mediastinal follicular dendritic cell sarcoma (FDCS) is extremely rare. Due to potential under-recognization of this disease, it happens to be misdiagnosed, especially on core needle biopsy. We report 3 cases of mediastinal FDCS and provide a literature review to improve better understanding of the tumor and to reduce misdiagnosis. Methods Three cases of mediastinal FDCS in our clinic practice were studied, including their core needle biopsy and resected specimens, and those cases reported previously in English literature were retrieved and analyzed. Results The core needle biopsy of case 1 showed a tumor reminiscent of classical Hodgkin’s lymphoma (CHL), while the resected mass was finally diagnosed with FDCS combined with hyaline-vascular Castleman’s disease. Both the biopsy and resected tissue of case 2 were constitutive of the clear epithelioid cells with marked atypia. In both cases, definitive diagnoses were not made on core needle biopsy. In case 3, there were some areas morphologically similar to CHL, and some areas contained ovoid to spindle-shaped tumor cells with fascicular pattern. The analysis of 43 cases of mediastinal FDCS showed the age of patients were from 16 to 76 years old, the male to female ratio was 1.5:1, the maximal tumor diameters were 3–17 cm. 18 cases were underwent preoperative biopsy, whereas 15 (83.3%) of which were misdiagnosed initially, often as lymphoma. 32 patients had available follow-up data, the rates of recurrence, metastasis, and mortality were 12.5, 18.8 and 28.1%, respectively. Current limited data suggested no statistical differences between adverse prognosis and gender, age, tumor size, necrosis, or different therapeutics, respectively. Conclusions Mediastinal FDCS is a rare malignancy that has yet not been fully understood and been often misdiagnosed, particularly when making a diagnosis on core needle biopsy. Increased awareness of this enigmatic tumor is crucial to avoid diagnostic pitfalls.

Purpose: To investigate the expression of hypoxia-inducible factor prolyl hydroxylase 3 (HIFPH3) in non-small cell lung cancer (NSCLC) and explore the correlation of HIFPH3 expression with lymph node metastasis and microvessel density (MVD). Materials and Methods: A total of 73 cases of NSCLC specimens, 24 cases of paracancerous tissues, and 20 normal pulmonary tissues were collected for HIFPH3 and CD31 immunohistochmical (IHC) study. Microvessel density (MVD) of the NSCLC tissues was also determined based on the expression of CD31. Results: The expression of HIFPH3 in carcinoma tissue was statistically higher than para-cancerous and normal pulmonary tissues (χ 2 =48.806, p

To investigate the distribution patterns and proliferative activity of lymphatic vessels in colorectal carcinomas (CRC) and their relationship with tumor metastasis and disease prognosis.The microlymphatic density (MLD) and microvascular density in tumoral and non-tumoral areas of 96 cases of CRC were evaluated by immunohistochemistry, using monoclonal antibodies for podoplanin and CD34 respectively. The Ki-67 expression of the lymphatic and blood vessels was detected by double-labeling immunohistochemistry. The relationship between MLD and clinicopathologic features and prognosis was analyzed.The lymph vessels at central and superficia1 portions of CRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at the tumor borders had large and open lumina. The MLD at tumor borders (51.2 +/- 25.5) was significantly higher than that in normal colorectal mucosa (29.4 +/- 9.0) and other portions of CRC (P0.01). The Ki-67 labeling index of the lymphatic lining cells at tumor borders (0.23 +/- 0.17) was significantly higher than that in other portions of CRC (P0.05). The MLD significantly correlated with lymphatic involvement by tumor cells, regional lymph node metastasis and distant metastasis (P0.01). The 5-year survival rate was also significantly lower in patients with high MLD (P0.05).Neolymphatic vessels are commonly seen in CRC, especially at tumor borders. High MLD at tumor borders is associated with metastasis. The detection of MLD at tumor borders may thus be useful in predicting lymph node metastasis and prognosis in patients with CPC.

Expression of survivin, an apoptosis suppressor gene, in colorectal cancer(CRC), and its relationship with pathologic factors, cell apoptosis, and angiogenesis are unclear. This study aimed to investigate the effect of survivin on cell apoptosis, and its relation with angiogenesis, and to further explore the effects of survivin on development and prognosis of CRC.Protein expression of survivin, and vascular endothelial growth factor (VEGF) in 91 specimens of CRC was detected by immunohistochemistry, apoptosis index (AI) of tumor cells was detected by TUNEL method.Positive rate of survivin in CRC with distant metastasis was 56.0% (14/25), significantly higher than that in CRC without metastasis (48.5%, 32/66) (P0.05); and that in 5-year survival patients(42.9%,30/70) was lower than that in patients died within 5 years (76.2%,16/21) (P0.01). The average survival time of patients with positive expression of survivin was 91.3 months, and that of patients with negative expression of survivin was 116.4 months; 5-year survival rate of the former (65.2%, 30/46) was significantly lower than that of the latter (88.9%, 40/45) (P0.01). The average AI of patients with positive expression of survivin was lower than that of patients with negative expression of survivin [(0.74+/-0.19)% vs. (1.07+/-0.24)%, P0.01]; the expression of survivin significantly correlated with that of VEGF (pearson: 0.721).Survivin may promote metastasis, and affect prognosis of CRC through inhibiting cell apoptosis, and regulating angiogenesis of CRC.