Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker

Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer.Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The “survival” and “GSVA” package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model.Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared.Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer

The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and the Wnt/β-catenin pathway, as well as the dynamics of exosome and cellular metabolism. Finally, we discuss the implications of the highly plastic nature and epigenetic susceptibility of CD151 expression, function, and signaling for clinical diagnosis and therapeutic intervention for human cancer

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients.</p> <p>Methods</p> <p>2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed.</p> <p>Results</p> <p>Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found.</p> <p>Conclusion</p> <p>Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.</p

MiR–20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells

Additional file 3: Figure S2. The protein level of PARP and caspase3 detected by western in NCM, 5PM, NCA, 5PA, si-NC and si-Rab27B transfected CNE-2 and CNE-1 cells respectively

Analyses of hypoxia-related risk factors and clinical relevance in breast cancer

IntroductionHypoxia plays an important role in the heterogeneity, relapse, metastasis, and drug resistance of breast cancer. In this study, we explored the hypoxia-related biological signatures in different subtypes of breast cancer and identified the key prognostic factors by bioinformatics methods.MethodsBased on The Cancer Genome Atlas (TCGA) Breast Cancer datasets, we divided the samples into immune-activated/suppressed populations by single-sample gene set enrichment analysis (ssGSEA) and then used hierarchical clustering to further identify hypoxic/non-hypoxic populations from the immune-suppressed samples. A hypoxia related risk model of breast cancer was constructed.ResultsNuclear factor interleukin-3 regulated (NFIL3), serpin family E member 1 (SERPINE1), FOS, biglycan (BGN), epidermal growth factor receptor (EGFR), and sushi-repeat-containing protein, X-linked (SRPX) were identified as key hypoxia-related genes. Margin status, American Joint Committee on Cancer (AJCC) stage, hypoxia status, estrogen receptor/progesterone receptor (ER/PR) status, NFIL3, SERPINE1, EGFR, and risk score were identified as independent prognostic indicators for breast cancer patients. The 3- and 5-year survival curves of the model and immunohistochemical staining on the breast cancer microarray verified the statistical significance and feasibility of our model. Among the different molecular types of breast cancer, ER/PR+ and HER2+ patients might have higher hypoxia-related risk scores. ER/PR-negative samples demonstrated more activated immune-related pathways and better response to most anticancer agents.DiscussionOur study revealed a novel risk model and potential feasible prognostic factors for breast cancer and might provide new perspectives for individual breast cancer treatment

An autophagic gene‐based signature to predict the survival of patients with low‐grade gliomas

Abstract Background Since autophagy remains an important topic of investigation, the RNA‐sequence profiles of autophagy‐related genes (ARGs) can provide insights into predicting low‐grade gliomas (LGG) prognosis. Methods The RNA‐seq profiles of autophagic genes and prognosis data of LGG were integrated from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model were carried out to identify the differentially expressed prognostic autophagy‐related genes. Then, the autophagic‐gene signature was formed and verified in TCGA test set and external CGGA cohorts. Time‐dependent receiver operating characteristic (ROC) was examined to test the accuracy of this signature feature. A nomogram was conducted to meet the needs of clinicians. Sankey diagrams were performed to visualize the relationship between the multigene signatures and clinic‐pathological features. Results Twenty‐four ARGs were finally identified most relevant to LGG prognosis. According to the specific prediction index formula, the patients were classified into low‐risk or high‐risk groups. Prognostic accuracy was proved by time‐dependent ROC analysis, with AUC 0.9, 0.93, and 0.876 at the survival time of 2‐, 3‐, and 5‐year, respectively, which was superior to the AUC of the isocitrate dehydrogenase (IDH) mutation. The result was confirmed while validated in the TCGA test set and external validation CGGA cohort. A nomogram was constructed to meet individual needs. With a visualization approach, Sankey diagrams show the relationship of the histological type, IDH status, and predict index. In TCGA and CGGA cohorts, both low‐risk groups displayed better survival rate in LGG while histological type and IDH status did not show consistency results. Conclusions 24‐ARGs may play crucial roles in the progression of LGG, and LGG patients were effectively divided into low‐risk and high‐risk groups according to prognostic prediction. Overall, our study will provide novel strategies for clinical applications

Trastuzumab-induced thrombocytopenia after eight cycles of trastuzumab treatment

Trastuzumab, a humanized monoclonal antibody derived from recombinant DNA, is used in patients with breast cancer with HER2 gene amplification. The survival benefit from trastuzumab has been well established in patients with early and metastatic breast cancer who had over expression of HER2. We reported a case of severe thrombocytopenia after eight cycles of trastuzumab treatment for breast cancer. Before the 9th trastuzumab treatment, the patient’s platelet decreased to 48 × 109/L. Recombinant human thrombopoietin was used, and the platelet level increased to normal level. Before the 10th treatment, the platelet count of the patient was 99 × 109/L. However, during the 10th and 11th trastuzumab treatment, the platelet count decreased to 5 × 109/L in 24 h. After treatment with TPO and corticosteroids, the platelet levels increased to the normal level in 7 days. Trastuzumab-induced thrombocytopenia is rare but still occurred even after 8 cycles of trastuzumab treatment