Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

A Cost-Effective Model for Predicting Recurrent Gastric Cancer Using Clinical Features.

This study used artificial intelligence techniques to identify clinical cancer biomarkers for recurrent gastric cancer survivors. From a hospital-based cancer registry database in Taiwan, the datasets of the incidence of recurrence and clinical risk features were included in 2476 gastric cancer survivors. We benchmarked Random Forest using MLP, C4.5, AdaBoost, and Bagging algorithms on metrics and leveraged the synthetic minority oversampling technique (SMOTE) for imbalanced dataset issues, cost-sensitive learning for risk assessment, and SHapley Additive exPlanations (SHAPs) for feature importance analysis in this study. Our proposed Random Forest outperformed the other models with an accuracy of 87.9%, a recall rate of 90.5%, an accuracy rate of 86%, and an F1 of 88.2% on the recurrent category by a 10-fold cross-validation in a balanced dataset. We identified clinical features of recurrent gastric cancer, which are the top five features, stage, number of regional lymph node involvement, Helicobacter pylori, BMI (body mass index), and gender; these features significantly affect the prediction model's output and are worth paying attention to in the following causal effect analysis. Using an artificial intelligence model, the risk factors for recurrent gastric cancer could be identified and cost-effectively ranked according to their feature importance. In addition, they should be crucial clinical features to provide physicians with the knowledge to screen high-risk patients in gastric cancer survivors as well.

A Customized Energy Management System for Distributed PV, Energy Storage Units, and Charging Stations on Kinmen Island of Taiwan.

Kinmen, the famous Cold War island also known as Quemoy, is a typical island with isolated power grids. It considers the promotion of renewable energy and electric charging vehicles to be two essential strategies to achieve the goal of a low-carbon island and smart grid. With this motivation in mind, the main objective of this study is to design and deploy an energy management system for hundreds of current PV sites distributed on the island, energy storage systems, and charging stations on the island. In addition, the real-time acquisition of the data for power generation, power storage, and power consumption systems will be used for future demand and response analysis. Moreover, the accumulated dataset will also be utilized for the forecast or prediction of renewable energy generated by the PV systems or power consumed by the battery units or charging stations. The results of this study are promising since a practical, robust, and workable system and database are developed and implemented with a variety of Internet of Things (IoT), data transmission technologies, and the hybrid of on-premises and cloud servers. Users of the proposed system can remotely access the visualized data through the user-friendly web-based and Line bot interfaces seamlessly.

Perturbation Analysis of a Prognostic DDX3X-Mediated Gene Expression Signature Identifies the Antimetastatic Potential of Chaetocin in Hepatocellular Carcinoma.

ATP-dependent RNA helicase DDX3X, also known as DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 3, X-Linked (DDX3X), is critical for RNA metabolism, and emerging evidence implicates ATP-dependent RNA helicase DDX3X's participation in various cellular processes to modulate cancer progression. In this study, the clinical significance of DDX3X was addressed, and DDX3X was identified as a biomarker for poor prognosis. An exploration of transcriptomic data from 373 liver cancer patients from The Cancer Genome Atlas (TCGA) using Ingenuity Pathway Analysis (IPA) suggested an association between DDX3X expression and cancer metastasis. Lentiviral-based silencing of DDX3X in a hepatocellular carcinoma (HCC) cell line resulted in the suppression of cell migration and invasion. The molecular mechanism regarding ATP-dependent RNA helicase DDX3X in liver cancer progression had been addressed in many studies. I focused on the biological application of the DDX3X-mediated gene expression signature in cancer therapeutics. An investigation of the DDX3X-correlated expression signature via the L1000 platform of Connectivity Map (BROAD Institute) first identified a histone methyltransferase inhibitor, chaetocin, as a novel compound for alleviating metastasis in HCC. In this study, the prognostic value of DDX3X and the antimetastatic property of chaetocin are presented to shed light on the development of anti-liver cancer strategies.

RUNX2 and Cancer.

Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer have attracted attention and led RUNX2 to be considered a biomarker for cancer. Many discoveries have illustrated the indirect and direct biological functions of RUNX2 in orchestrating cancer stemness, cancer metastasis, angiogenesis, proliferation, and chemoresistance to anticancer compounds, warranting further exploration of the associated mechanisms to support the development of a novel therapeutic strategy. In this review, we focus mainly on critical and recent research developments, including RUNX2's oncogenic activities, by summarizing and integrating the findings on somatic mutations of RUNX2, transcriptomic studies, clinical information, and discoveries about how the RUNX2-induced signaling pathway modulates malignant progression in cancer. We also comprehensively discuss RUNX2 RNA expression in a pancancer panel and in specific normal cell types at the single-cell level to indicate the potential cell types and sites for tumorigenesis. We expect this review to shed light on the recent mechanistical findings and modulatory role of RUNX2 in cancer progression and provide biological information that can guide new research in this field.

Deep Learning Algorithms with LIME and Similarity Distance Analysis on COVID-19 Chest X-ray Dataset.

In the last few years, many types of research have been conducted on the most harmful pandemic, COVID-19. Machine learning approaches have been applied to investigate chest X-rays of COVID-19 patients in many respects. This study focuses on the deep learning algorithm from the standpoint of feature space and similarity analysis. Firstly, we utilized Local Interpretable Model-agnostic Explanations (LIME) to justify the necessity of the region of interest (ROI) process and further prepared ROI via U-Net segmentation that masked out non-lung areas of images to prevent the classifier from being distracted by irrelevant features. The experimental results were promising, with detection performance reaching an overall accuracy of 95.5%, a sensitivity of 98.4%, a precision of 94.7%, and an F1 score of 96.5% on the COVID-19 category. Secondly, we applied similarity analysis to identify outliers and further provided an objective confidence reference specific to the similarity distance to centers or boundaries of clusters while inferring. Finally, the experimental results suggested putting more effort into enhancing the low-accuracy subspace locally, which is identified by the similarity distance to the centers. The experimental results were promising, and based on those perspectives, our approach could be more flexible to deploy dedicated classifiers specific to different subspaces instead of one rigid end-to-end black box model for all feature space.

Updated Functional Roles of NAMPT in Carcinogenesis and Therapeutic Niches.

Nicotinamide phosphoribosyltransferase (NAMPT) is notable for its regulatory roles in tumor development and progression. Emerging evidence regarding NAMPT somatic mutations in cancer patients, NAMPT expressional signatures in normal tissues and cancers, and the prognostic significance of NAMPT in many cancer types has attracted attention, and NAMPT is considered a potential biomarker of cancer. Recent discoveries have demonstrated the indirect association and direct biological functions of NAMPT in modulating cancer metastasis, proliferation, angiogenesis, cancer stemness, and chemoresistance to anticancer drugs. These findings warrant further investigation of the underlying mechanisms to provide knowledge for developing novel cancer therapeutics. In this review article, we explore recent research developments involving the oncogenic activities of NAMPT by summarizing current knowledge regarding NAMPT somatic mutations, clinical trials, transcriptome data, and clinical information and discoveries related to the NAMPT-induced signaling pathway in modulating hallmarks of cancer. Furthermore, the comprehensive representation of NAMPT RNA expression in a pancancer panel as well as in specific normal cell types at single-cell level are demonstrated. The results suggest potential sites and cell types that could facilitate NAMPT-related tumorigenesis. With this review, we aim to shed light on the regulatory roles of NAMPT in tumor development and progression, and provide information to guide future research directions in this field.

RUNX1 and cancer.

Runt-related transcription factor 1 (RUNX1) is frequently involved in the progression of acute leukemia. However, emerging and discoverable RUNX1 somatic mutations, RUNX1 expressional signatures in normal tissues and cancers, and RUNX1's clinical significance in many cancer types have attracted attention for considering RUNX1 as a biomarker for cancer. Recent discoveries have demonstrated the indirect and direct biological functions of RUNX1 in modulating cancer metastasis, proliferation, angiogenesis, cancer stemness and chemoresistance to anticancer drugs, warranting the further investigations of the underlying mechanisms to provide knowledge for developing a novel therapeutic approach. In this review article, we focused mainly on recent research developments involving oncogenic activities of RUNX1 by summarizing and integrating RUNX1 somatic mutations, clinical trials, transcriptome data, clinical information and the discoveries related to the RUNX1-induced signaling pathway in modulating malignant phenotypes. Furthermore, a comprehensive demonstration of RUNX1 RNA expression in a pancancer panel and specific normal cell types at single-cell level were presented, and the results suggest potential sites and cell types of RUNX1-related tumorigenesis. With this review, we aim to shed light on the understanding of the regulatory role of RUNX1 in cancer progression, and provide information for guiding potential research directions in this field.

Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma.

Mutational profiling of patients' tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (p = 0.0005) and overall survival (p = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (p = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy.

Leptin Is Associated with Poor Clinical Outcomes and Promotes Clear Cell Renal Cell Carcinoma Progression.

Emerging evidence has shown the oncogenic roles of leptin in modulating cancer progression in addition to its original roles. Analyses of transcriptomic data and patients' clinical information have revealed leptin's prognostic significance in renal cell carcinoma (RCC). However, its biological effects on RCC progression have not yet been explored. Clinical and transcriptomic data of a RCC cohort of 603 patients were retrieved from The Cancer Genome Atlas (TCGA) and analyzed to reveal the correlation of leptin with clinical outcomes and the hierarchical clustering of gene signatures based on leptin levels. In addition, cox univariate and multivariate regression analyses, cell migration upon leptin treatment, identification of putative leptin-regulated canonical pathways via ingenuity pathway analysis (IPA), and the investigation of induction of Wnt5a, ROR2, and Jun N-terminal Kinases (JNK) phosphorylation activation were performed. We first observed a correlation of high leptin levels and poor outcomes in RCC patients. Knowledge-based analysis by IPA indicated the induction of cancer cell migration by leptin, which was manifested via direct leptin treatment in the RCC cell lines. In RCC patients with high leptin levels, the planar cell polarity (PCP)/JNK signaling pathway was shown to be activated, and genes in the axis, including CTHRC1, FZD2, FZD10, ROR2, WNT2, WNT4, WNT10B, WNT5A, WNT5B, and WNT7B, were upregulated. All of these genes were associated with unfavorable clinical outcomes. WNT5A and ROR2 are pivotal upstream regulators of PCP/JNK signaling, and their correlations with leptin expression levels were displayed by a Pearson correlation analysis. The inhibition of signal transduction by SP600125 reversed leptin-mediated cell migration properties in RCC cell lines. The results indicate the prognostic impact of leptin on RCC patients and uncover its ability to promote cell migration via PCP/JNK signaling.

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments.

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

Functional Roles of SPINK1 in Cancers.

Serine Peptidase Inhibitor Kazal Type 1 (SPINK1) is a secreted protein known as a protease inhibitor of trypsin in the pancreas. However, emerging evidence shows its function in promoting cancer progression in various types of cancer. SPINK1 modulated tumor malignancies and induced the activation of the downstream signaling of epidermal growth factor receptor (EGFR) in cancer cells, due to the structural similarity with epidermal growth factor (EGF). The discoverable SPINK1 somatic mutations, expressional signatures, and prognostic significances in various types of cancer have attracted attention as a cancer biomarker in clinical applications. Emerging findings further clarify the direct and indirect biological effects of SPINK1 in regulating cancer proliferation, metastasis, drug resistance, transdifferentiation, and cancer stemness, warranting the exploration of the SPINK1-mediated molecular mechanism to identify a therapeutic strategy. In this review article, we first integrate the transcriptomic data of different types of cancer with clinical information and recent findings of SPINK1-mediated malignant phenotypes. In addition, a comprehensive summary of SPINK1 expression in a pan-cancer panel and individual cell types of specific organs at the single-cell level is presented to indicate the potential sites of tumorigenesis, which has not yet been reported. This review aims to shed light on the roles of SPINK1 in cancer and provide guidance and potential directions for scientists in this field.

Expression of heme oxygenase-1 in type II pneumocytes protects against heatstroke-induced lung damage.

Heatstroke (HS) is an acute clinical disease characterized by abnormal hyperthermia and multi-organ dysfunction. Heme oxygenase (HO)-1, also called heat shock protein (HSP)32, is induced by hyperthermia and also plays protective roles in many lung disease models. Based on this phenomenon, we investigated the protective role of endogenous HO-1 in heat-induced lung damage in rats. Male Sprague-Dawley (SD) rats were separated into three groups: (a) normothermic sham, (b) HS, and (c) SnPP (inhibitor of HO-1) pretreatment rats. In the HS group, rats were killed at various time points (1, 3, 6, and 12 h after heat exposure) in order to analyze messenger ribonucleic acid (mRNA) and protein levels. Lung sections were examined for tissue damage and localization of HO-1 using immunofluorescence double labeling. We found that HS induced lung pathology (congested and thickened lung septa). The level of HO-1 mRNA was increased at 1 h, and the protein level peaked at 6 h after heat exposure. Pretreatment with SnPP (tin-protoporphyrin IX, 30 mg/kg, intraperitoneal injection for 1 h before heat exposure) aggravated the lung damage. Furthermore, we demonstrated HO-1 expression in lung type II pneumocytes. Our results suggest that endogenous HO-1 is protective against HS-induced lung damage. Induction of HO-1 may be a potential therapeutic strategy for treating heat-related diseases.

Ultrasensitive and specific two-photon fluorescence detection of hypochlorous acid by a lysosome-targeting fluorescent probe for cell imaging.

Hypochlorous acid (HOCl) is involved in numerous cellular processes, such as pathogen response, immune regulation, and anti-inflammation. Consequently, the development of HOCl detection at the cellular level has been an important issue in investigating the dynamic distributions of HOCl. Herein, a fluorescent probe, Lyso-NA, containing a HOCl-reactive aminophenol group and a lysosomal-targeting morpholine group, has been effectively designed for detecting lysosomal HOCl. The reaction of Lyso-NA with HOCl induces the oxidation of aminophenol and accompanied by a 136-fold fluorescence enhancement. The detection limit is found at 13 nM. The fluorescence enhancement is accomplished through the suppression of twisted intramolecular charge transfer (TICT). With morpholine, the probe Lyso-NA shows the great lysosomal targetable ability for imaging endogenous lysosomal HOCl in living cells and tissues by two-photon microscopy, providing an opportunity to monitor HOCl in the lysosomes for understanding its biological functions.

DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression.

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, DDX3X's role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to DDX3X. The results suggest that DDX3X is epigenetically repressed in tumor tissue and that lower DDX3X is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by DDX3X. Furthermore, SPINK1 and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with DDX3X in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low DDX3X. Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3Xlow/SPINK1high/metallothioneinhigh axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low DDX3X expression levels.

Gefitinib modulates stress fibers and tubular-like structure formation and attenuates angiogenesis in an in vivo chicken model of chorioallantoic membrane angiogenesis.

Gefitinib is an ATP-competitive inhibitor of receptor tyrosine kinases known to repress the progression of various types of cancers. Emerging evidence has shown that this molecule modulates endothelial cells to inhibit angiogenesis. However, the biological effects of gefitinib have not been comprehensively investigated in endothelial cells. In this study, gefitinib-mediated regulation of cell proliferation, migration, cell attachment, cytoskeletal actin filament reorganization, tubular-like structure formation and angiogenesis in vivo was examined along with the corresponding mechanisms. G1-phase cell cycle arrest was detected and led to a decrease in 3H-labeled thymidine incorporation under sublethal doses of gefitinib. Endothelial cell migration was blocked in both wound-healing and transwell assays. In addition, gefitinib simultaneously inhibited collagen- and fibronectin-dependent cell attachment. Importantly, we first observed that the gefitinib-induced phenotypes might be partially due to the abnormal retrograde flow of actin filaments. The results of this study revealed the antivasculogenic effects of gefitinib at sublethal doses and indicated that the treatment of cancer patients with this drug might impair angiogenesis in the tumor microenvironment to reduce the cancer metastasis rate in addition to the direct therapeutic benefits of repressing epidermal growth factor receptor signaling in cancer cells.

The role of visfatin in cancer proliferation, angiogenesis, metastasis, drug resistance and clinical prognosis.

Visfatin, also known as nicotinamide phosphoribosyltransferase or pre-B-cell colony-enhancing factor (PBEF), is an adipocytokine secreted by adipocytes, macrophages and inflamed endothelial tissue. Related reports have indicated a positive correlation between the visfatin level and obesity and cancer risk. In addition to its original function, visfatin is multifunctional and plays critical roles in the promotion of several processes relevant to cancer progression including cancer cell proliferation, angiogenesis, metastasis and drug resistance. The relative expression of visfatin and the potential visfatin receptor on a pan-cancer scale was determined based on the transcriptome analysis data in The Cancer Genome Atlas. We further show the clinical association of its signaling axis with the survival of cancer patients, which reveals its prognostic power for specific cancer types. This review illustrates visfatin's biological functions related to cancer progression and demonstrates its clinical significance in predicting outcomes of cancer patients.

Ghrelin Upregulates Oncogenic Aurora A to Promote Renal Cell Carcinoma Invasion.

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin's role in cancer progression. We previously characterized ghrelin's prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin's activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis.

DDX3X Multifunctionally Modulates Tumor Progression and Serves as a Prognostic Indicator to Predict Cancer Outcomes.

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-Linked (DDX3X), also known as DDX3, is one of the most widely studied and evolutionarily conserved members of the DEAD-box RNA helicase subfamily, and has been reported to participate in several cytosolic steps of mRNA metabolism. DDX3X facilitates the translation of specific targets via its helicase activity and regulates factors of the translation initiation complex. Emerging evidence illustrates the biological activities of DDX3X beyond its originally identified functions. The nonconventional regulatory effects include acting as a signaling adaptor molecule independent of enzymatic RNA remodeling, and DDX3X exhibits abnormal expression in cancers. DDX3X interacts with specific components to perform both oncogenic and tumor-suppressive roles in modulating tumor proliferation, migration, invasion, drug resistance, and cancer stemness in many types of cancers, indicating the need to unravel the associated molecular mechanisms. In this review article, we summarized and integrated current findings relevant to DDX3X in cancer research fields, cytokines and compounds modulating DDX3X's functions, and the released transcriptomic information and cancer patient clinical data from public databases. We found evidence for DDX3X having multiple impacts on cancer progression, and evaluated DDX3X expression levels in a pancancer panel and its associations with patient survival in each cancer-type cohort.

Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression.

Leptin is a peptide hormone that has been characterized as the ligand of leptin receptor (LEPR). The observation of leptin secretion and leptin receptor expression beyond the normal tissues suggests the potentially critical roles other than its physiological function. In addition to the original function in controlling appetite and energy expenditure, leptin-mediated signaling axis through leptin receptor is multifunctional which plays role in the regulation toward broad types of cancer. Emerging evidences has indicated leptin's function in promoting several processes which are relevant to cancer progression including cell proliferation, metastasis, angiogenesis and drug resistance. We relatively display leptin and leptin receptor expression levels in pan-cancer panel based on the transcriptome analysis via dataset The Cancer Genome Atlas (TCGA), and show the clinical association of the axis in predicting cancer prognosis. The results indicate the pathological impacts of this axis on many types of cancer. This review mainly focuses on leptin-mediated effects and its downstream signaling related to the progression of cancers, and displays the clinical significance of this axis including the impact on cancer patient survival.