Identification and Comprehensive Prognostic Analysis of a Novel Chemokine-Related lncRNA Signature and Immune Landscape in Gastric Cancer

Gastric cancer (GC) is a malignant tumor with poor survival outcomes. Immunotherapy can improve the prognosis of many cancers, including GC. However, in clinical practice, not all cancer patients are sensitive to immunotherapy. Therefore, it is essential to identify effective biomarkers for predicting the prognosis and immunotherapy sensitivity of GC. In recent years, chemokines have been widely reported to regulate the tumor microenvironment, especially the immune landscape. However, whether chemokine-related lncRNAs are associated with the prognosis and immune landscape of GC remains unclear. In this study, we first constructed a novel chemokine-related lncRNA risk model to predict the prognosis and immune landscape of GC patients. By using various algorithms, we identified 10 chemokine-related lncRNAs to construct the risk model. Then, we determined the prognostic efficiency and accuracy of the risk model. The effectiveness and accuracy of the risk model were further validated in the testing set and the entire set. In addition, our risk model exerted a crucial role in predicting the infiltration of immune cells, immune checkpoint genes expression, immunotherapy scores and tumor mutation burden of GC patients. In conclusion, our risk model has preferable prognostic performance and may provide crucial clues to formulate immunotherapy strategies for GC.

Ki-67 and breast cancer prognosis: does it matter if Ki-67 level is examined using preoperative biopsy or postoperative specimen?

Purpose This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen). Methods A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%. Results Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination. Conclusion Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing.

TWIST1 expression is associated with high-risk neuroblastoma and promotes primary and metastatic tumor growth

The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression with poor survival and metastasis in primary NB, while TWIST2 correlates with good prognosis. Secondly, suppression of TWIST1 by CRISPR/Cas9 results in a reduction of tumor growth and metastasis colonization in immunocompromised mice. Moreover, TWIST1 knockout tumors display a less aggressive cellular morphology and a reduced disruption of the extracellular matrix (ECM) reticulin network. Additionally, we identify a TWIST1-mediated transcriptional program associated with dismal outcome in NB and involved in the control of pathways mainly linked to the signaling, migration, adhesion, the organization of the ECM, and the tumor cells versus tumor stroma crosstalk. Taken together, our findings confirm TWIST1 as promising therapeutic target in NB.

A Case of Clinically Amyopathic Dermatomyositis that was Refractory to Intensive Immunosuppressive Therapy including Tofacitinib, but Successfully Treated with Plasma Exchange Therapy

ABSTRACT Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: 1) cytokines that were not suppressed by TOF played an important role in RP-ILD; 2) TOF was administered later than previously reported; and 3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.

Survival Outcomes of Patients With Mediastinal Germ Cell Tumors: Experience of a Cancer Center in South America

PurposeMediastinal germ cell tumors (GCT) are rare neoplasms associated with poor survival prognosis. Due to their low incidence, limited information is available about this disease in South America. The objective of this study is to report the clinical characteristics and outcomes of patients with mediastinal GCT in a cancer center in Colombia.Materials and MethodsWe conducted a retrospective analysis of patients with mediastinal GCT treated at the National Cancer Institute at Bogota (Colombia) between 2008 and 2020. Survival curves were presented using the Kaplan–Meier method. Chi-square and Cox proportional hazard model tests were used for data analysis.ResultsSixty-one patients were included in the study. Of them, 60 were male and 51 (83.6%) of whom had non-seminomatous germ cell tumors (NSGCT). Twenty-nine patients (47.5%) presented with superior vena cava syndrome, and 18 (29.5%) patients had extrapulmonary metastatic involvement. The three-year overall survival (OS) of NSGCT patients was 26%. The 3-year OS of NSGCT patients who underwent surgical resection of residual mediastinal mass after chemotherapy was 59%. Non-surgical management after first-line chemotherapy was associated with a worse survival prognosis in NSGCT patients (p = 0.002). Ten patients with mediastinal seminomatous germ cell tumors (SCGT) achieved a 3-year OS of 100%.ConclusionMediastinal NSGCT had poor outcomes. Surgery of the residual mass after first-line chemotherapy seems to improve the outcome of NSGCT patients. Advanced disease at presentation may reflect inadequate access to reference cancer centers in Colombia and potentially explain poor survival outcomes in this cohort. On the other hand, mediastinal SCGT is a biologically different disease; most patients will achieve disease remission and long-term survival with first-line chemotherapy.

ZC3H15 promotes glioblastoma progression through regulating EGFR stability

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved protein involved in several cellular processes, which was responsible for tumorigenesis and may be a promising marker in myeloid leukemia (AML) and hepatocellular carcinoma (HCC). However, little is known about the biological significance and molecular mechanisms of ZC3H15 in GBM. In this study, we revealed that ZC3H15 was overexpressed in GBM and high ZC3H15 expression was associated with poor survival of patients with GBM. We found that ZC3H15 promoted the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. We also revealed that ZC3H15 reduced EGFR ubiquitination, which was responsible for EGFR protein stabilization. In addition, we demonstrated that ZC3H15 inhibited the transcription of CBL, which was an E3 ubiquitin ligase for EGFR proteasomal degradation. And silencing of CBL could partly abrogate the inhibitory effects on cell proliferation, migration, and invasion of GBM cells induced by ZC3H15 knockdown. Thus, our research revealed the important roles of ZC3H15 in GBM development and provided a brand-new insight for improving the treatment of GBMs.

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients

Background: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. Method: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. Results: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26–0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. Conclusion: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.

High Expression of H2BC12 Predicts Poor Survival Outcome of Low-Grade Gliomas: A Study Based on TCGA Data

Purpose Low-grade gliomas (LGG) have highly variable clinical behaviors, with a high incidence of disease progression as 70% within ten years. Regardless of treatment combining surgery and radiotherapy or chemotherapy, LGG is still associated with adverse survival outcomes. Therefore, our study was performed to satisfy the increasing demand of novel sensitive biomarkers and therapeutic targets in treatment and diagnosis of LGG. Methods The TCGA data set was used to examine the relationship between H2BC12 expression and clinical pathologic characteristics. The significance of H2BC12 expression in prognosis was also investigated. In addition, H2BC12 expression-related pathways were enriched by gene set enrichment analysis (GSEA). Association analysis of H2BC12 gene expression and immune infiltration was performed by single sample gene set enrichment analysis (ssGSEA). Results Significantly up-regulated expression of H2BC12 mRNA was found in LGG tissue when compared to normal tissue and was proven to be diagnostic (have diagnostic significance) for LGG. In the meantime, high H2BC12 levels were associated with WHO grade, IDH status, 1p/19q codeletion, primary therapy outcome and histological type of LGG, and additionally, prognostic for adverse survival outcomes. In the multivariate analysis, high H2BC12 levels were identified to be an independent predictor for poor survival outcomes of LGG patients. Pathways in cancer, signaling by Wnt or PI3K-AKT signaling pathway, DNA repair, cellular senescence and DNA double strand break repair were differentially activated in the phenotype that positively associated with H2BC12. Conclusion H2BC12 is a promising biomarker for the diagnosis and prognosis of LGG.