Overexpression of heat shock protein 47 is associated with increased proliferation and metastasis in gastric cancer.

Here, we investigated that the heat shock protein 47 (HSP47) plays a crucial role in the progression of gastric cancer (GC). We analyzed HSP47 gene expression in GC cell lines and patient tissues. The HSP47 mRNA and protein expression levels were significantly higher in GC cell lines and tumor tissues compared to normal gastric mucosa. Using siRNA to silence the expression of HSP47 in GC cells resulted in a significant reduction in their proliferation, wound healing, migration, and invasion capacities. Additionally, we also showed that the mRNA expression of matrix metallopeptidase-7 (MMP-7), a metastasis-promoting gene, was significantly reduced in HSP47 siRNA-transfected GC cells. We confirmed that the HSP47 promoter region was methylated in the SNU-216 GC cell line expressing low levels of HSP47 and in most non-cancerous gastric tissues. It means that the expression of HSP47 is regulated by epigenetic regulatory mechanisms. These findings suggest that targeting HSP47, potentially through its promoter methylation, could be a useful new therapeutic strategy for treating GC.

vSPACE: Exploring Virtual Spatial Representation of Articular Chondrocytes at the Single-Cell Level.

Single cell RNA sequencing technology has been dramatically changing how gene expression studies are performed. However, its use has been limited to identifying subtypes of cells by comparing cells' gene expression levels in an unbiased manner to produce a 2D plot (e.g., UMAP/tSNE). We developed a new method of placing cells in 2D space. This system, called vSPACE, shows a virtual spatial representation of scRNAseq data obtained from human articular cartilage by emulating the concept of spatial transcriptomics technology, but virtually. This virtual 2D plot presentation of human articular cartage cells generates several zonal distribution patterns, in one or multiple genes at a time, reveling patterns that scientists can appreciate as imputed spatial distribution patterns along the zonal axis. The discovered patterns are explainable and remarkably consistent across all six healthy doners despite their respectively different clinical variables (age and sex), suggesting the confidence of the discovered patterns.

Solar-driven surface-heating membrane distillation using Ti3C2Tx MXene-coated spacers.

The emergence of two-dimensional (2D) MXenes as efficient light-to-heat conversion materials offers significant potential for solar-based desalination, particularly in photothermal interfacial evaporation, enabling cost-effective solar-powered membrane distillation (MD). This study investigates solar-powered MD afforded by a photothermally functionalized spacer, which is built by spray-coating Ti3C2Tx MXene sheets on metallic spacers. 2D Ti3C2Tx MXene gives an ultrahigh photothermal conversion efficiency; thereby, by Ti3C2Tx MXene-coated metallic spacer, this rationally designed spacer allows for a localized photothermal conversion and interfacial feed heating effect on the membrane surface, especially for MD operation. As a feed spacer and a photothermal element, Ti3C2Tx MXene-coated metallic spacer exhibited stable enhanced water flux of up to 0.36 kg·m-2h-1 under one sun illumination for a feed salinity of 35 g·L-1, corresponding energy conversion efficiency of 28.3 %. Overall, the developed photothermal Ti3C2Tx MXene-coated spacers displayed great potential in enhancing the performance, scalability, and feasibility of solar-driven MD process, paving the way for further development of photothermal elements that can be implemented in solar MD applications.

Electrothermal interfacial evaporation through carbon-nanostructured composite membranes.

High energy demand required in membrane distillation (MD) process to heat feed water and maintain the necessary temperature gradient across the membrane presents a challenge to widespread adoption of MD. In response to this challenge, surface heating membrane distillation (SHMD) has emerged as a promising solution. SHMD can employ solar or electrical energy to directly heat the membrane and feed, eliminating the need for an external heat source to heat feed water. In this study, we explore electrothermally-driven interfacial evaporation using a multi-walled carbon nanotube (MWCNT)-based composite membrane and further envision its utilization for high-efficient SHMD. Upon application of voltage, the resistance of the MWCNT leads to the conversion of electrical energy into heat, which is then uniformly transferred to feeds. The MWCNT-based composite membrane exhibited an evaporative water flux of up to 2.34 kg m-2h-1 with an associated energy efficiency of 61% and demonstrated outstanding localized surface heating performance. The employed membranes exhibited no significant variations in either resistance or surface temperature, regardless of the direction of the applied electric field. Energy parameters from the electrothermal membranes showed quantitative agreement with values reported for various electrothermal MD systems, suggesting the potential of the composite membranes in energy-efficient and cost-effective localized heating MD applications.

CGCom: a framework for inferring Cell-cell Communication based on Graph Neural Network.

Cell-cell communication is crucial in maintaining cellular homeostasis, cell survival and various regulatory relationships among interacting cells. Thanks to recent advances of spatial transcriptomics technologies, we can now explore if and how cells' proximal information available from spatial transcriptomics datasets can be used to infer cell-cell communication. Here we present a cell-cell communication inference framework, called CGCom, which uses a graph neural network (GNN) to learn communication patterns among interacting cells by combining single-cell spatial transcriptomic datasets with publicly available ligand-receptor information and the molecular regulatory information down-stream of the ligand-receptor signaling. To evaluate the performance of CGCom, we applied it to mouse embryo seqFISH datasets. Our results demonstrate that CGCom can not only accurately infer cell communication between individual cell pairs but also generalize its learning to predict communication between different cell types. We compared the performance of CGCom with two existing methods, CellChat and CellPhoneDB, and our comparative study revealed both common and unique communication patterns from the three approaches. Commonly found communication patterns include three sets of ligand-receptor communication relationships, one between surface ectoderm cells and spinal cord cells, one between gut tube cells and endothelium, and one between neural crest and endothelium, all of which have already been reported in the literature thus offering credibility of all three methods. However, we hypothesize that CGCom is superior in reducing false positives thanks to its use of cell proximal information and its learning between specific cell pairs rather than between cell types. CGCom is a GNN-based solution that can take advantage of spatially resolved single-cell transcriptomic data in predicting cell-cell communication with a higher accuracy.

Photothermal Surface Heating Membrane Distillation Using 3D-Printed Ti3C2Tx MXene-Based Nanocomposite Spacers.

To address the growing global need for freshwater, it has become essential to use nonpotable saline water. Solar membrane distillation is a potential desalination method that does not need conventional electricity and may cut water production costs. In this study, we develop a photothermal surface heating membrane distillation using a new class of photothermal spacers constructed with Ti3C2Tx MXene-based nanocomposites. In contrast to traditional membrane distillation, which utilizes energy-intensive bulk feed heating, solar-powered surface heating membrane distillation removes the external thermal energy input requirements, hence reducing operating costs significantly. In particular, three-dimensional (3D)-printing technology was used to fabricate the functional spacer, which allowed the design and materials to be fine-tuned per the needs of the process. Under solar illumination, the printed spacer can exhibit a localized photothermal conversion-driven heating effect near the surface of distillation membranes, which generates vapor pressure strong enough to operate distillation across membranes. Importantly, a two-dimensional Ti3C2Tx MXene with outstanding photothermal conversion efficiency and stability in hypersaline ionic solutions was incorporated into the 3D-printed spacers as the crucial nanofiller for imparting a local heating effect of feed. The fabricated nanocomposite spacers showed superior photothermal heating response under sunlight with an average permeate flux and energy conversion efficiency of 0.49 kg·m-2·h-1 and 30.6%, respectively. An enhancement in both photothermal efficiency and permeate flux was noticed as the amount of MXene nanosheets increased in the 3D-printed spacers. This study demonstrates the feasibility of using 3D-printed photothermal spacers for high-performance and sustainable surface heating membrane distillation, providing a promising avenue for further improvement with other photothermal nanofillers or spacer modifications.

Multi-Sensor Data Fusion with a Reconfigurable Module and Its Application to Unmanned Storage Boxes.

We present a multi-sensor data fusion model based on a reconfigurable module (RM) with three fusion layers. In the data layer, raw data are refined with respect to the sensor characteristics and then converted into logical values. In the feature layer, a fusion tree is configured, and the values of the intermediate nodes are calculated by applying predefined logical operations, which are adjustable. In the decision layer, a final decision is made by computing the value of the root according to predetermined equations. In this way, with given threshold values or sensor characteristics for data refinement and logic expressions for feature extraction and decision making, we reconstruct an RM that performs multi-sensor fusion and is adaptable for a dedicated application. We attempted to verify its feasibility by applying the proposed RM to an actual application. Considering the spread of the COVID-19 pandemic, an unmanned storage box was selected as our application target. Four types of sensors were used to determine the state of the door and the status of the existence of an item inside it. We implemented a prototype system that monitored the unmanned storage boxes by configuring the RM according to the proposed method. It was confirmed that a system built with only low-cost sensors can identify the states more reliably through multi-sensor data fusion.

Porous Ti3C2Tx MXene Membranes for Highly Efficient Salinity Gradient Energy Harvesting.

Extracting osmotic energy through nanoporous membranes is an efficient way to harvest renewable and sustainable energy using the salinity gradient between seawater and river water. Despite recent advances of nanopore-based membranes, which have revitalized the prospect of blue energy, their energy conversion is hampered by nanomembrane issues such as high internal resistance or low selectivity. Herein, we report a lamellar-structured membrane made of nanoporous Ti3C2Tx MXene sheets, exhibiting simultaneous enhancement in permeability and ion selectivity beyond their inherent trade-off. The perforated nanopores formed by facile H2SO4 oxidation of the sheets act as a network of cation channels that interconnects interplanar nanocapillaries throughout the lamellar membrane. The constructed internal nanopores lower the energy barrier for cation passage, thereby boosting the preferential ion diffusion across the membrane. A maximum output power density of the nanoporous Ti3C2Tx MXene membranes reaches up to 17.5 W·m-2 under a 100-fold KCl gradient at neutral pH and room temperature, which is as high as by 38% compared to that of the pristine membrane. The membrane design strategy employing the nanoporous two-dimensional sheets provides a promising approach for ion exchange, osmotic energy extraction, and other nanofluidic applications.

Predicting the targets of IRF8 and NFATc1 during osteoclast differentiation using the machine learning method framework cTAP.

BACKGROUND: Interferon regulatory factor-8 (IRF8) and nuclear factor-activated T cells c1 (NFATc1) are two transcription factors that have an important role in osteoclast differentiation. Thanks to ChIP-seq technology, scientists can now estimate potential genome-wide target genes of IRF8 and NFATc1. However, finding target genes that are consistently up-regulated or down-regulated across different studies is hard because it requires analysis of a large number of high-throughput expression studies from a comparable context. METHOD: We have developed a machine learning based method, called, Cohort-based TF target prediction system (cTAP) to overcome this problem. This method assumes that the pathway involving the transcription factors of interest is featured with multiple "functional groups" of marker genes pertaining to the concerned biological process. It uses two notions, Gene-Present Sufficiently (GP) and Gene-Absent Insufficiently (GA), in addition to log2 fold changes of differentially expressed genes for the prediction. Target prediction is made by applying multiple machine-learning models, which learn the patterns of GP and GA from log2 fold changes and four types of Z scores from the normalized cohort's gene expression data. The learned patterns are then associated with the putative transcription factor targets to identify genes that consistently exhibit Up/Down gene regulation patterns within the cohort. We applied this method to 11 publicly available GEO data sets related to osteoclastgenesis. RESULT: Our experiment identified a small number of Up/Down IRF8 and NFATc1 target genes as relevant to osteoclast differentiation. The machine learning models using GP and GA produced NFATc1 and IRF8 target genes different than simply using a log2 fold change alone. Our literature survey revealed that all predicted target genes have known roles in bone remodeling, specifically related to the immune system and osteoclast formation and functions, suggesting confidence and validity in our method. CONCLUSION: cTAP was motivated by recognizing that biologists tend to use Z score values present in data sets for the analysis. However, using cTAP effectively presupposes assembling a sizable cohort of gene expression data sets within a comparable context. As public gene expression data repositories grow, the need to use cohort-based analysis method like cTAP will become increasingly important.

rPAC: Route based pathway analysis for cohorts of gene expression data sets.

Pathway analysis is a popular method aiming to derive biological interpretation from high-throughput gene expression studies. However, existing methods focus mostly on identifying which pathway or pathways could have been perturbed, given differential gene expression patterns. In this paper, we present a novel pathway analysis framework, namely rPAC, which decomposes each signaling pathway route into two parts, the upstream portion of a transcription factor (TF) block and the downstream portion from the TF block and generates a pathway route perturbation analysis scheme examining disturbance scores assigned to both parts together. This rPAC scoring is further applied to a cohort of gene expression data sets which produces two summary metrics, "Proportion of Significance" (PS) and "Average Route Score" (ARS), as quantitative measures discerning perturbed pathway routes within and/or between cohorts. To demonstrate rPAC's scoring competency, we first used a large amount of simulated data and compared the method's performance against those by conventional methods in terms of power curve. Next, we performed a case study involving three epithelial cancer data sets from The Cancer Genome Atlas (TCGA). The rPAC method revealed specific pathway routes as potential cancer type signatures. A deeper pathway analysis of sub-groups (i.e., age groups in COAD or cancer sub-types in BRCA) resulted in pathway routes that are known to be associated with the sub-groups. In addition, multiple previously uncharacterized pathways routes were identified, potentially suggesting that rPAC is better in deciphering etiology of a disease than conventional methods particularly in isolating routes and sections of perturbed pathways in a finer granularity.

Muscle Fatigue Sensor Based on Ti3 C2 Tx MXene Hydrogel.

MXene-based hydrogels have received significant attention due to several promising properties that distinguish them from conventional hydrogels. In this study, it is shown that both strain and pH level can be exploited to tune the electronic and ionic transport in MXene-based hydrogel (M-hydrogel), which consists of MXene (Ti3 C2 Tx )-polyacrylic acid/polyvinyl alcohol hydrogel. In particular, the strain applied to the M-hydrogel changes MXene sheet orientation which leads to modulation of ionic transport within the M-hydrogel, due to strain-induced orientation of the surface charge-guided ionic pathway. Simultaneously, the reorientation of MXene sheets under the axial strain increases the electronic resistance of the M-hydrogel due to the loss of the percolative network of conductive MXene sheets during the stretching process. The iontronic characteristics of the M-hydrogel can thus be tuned by strain and pH, which allows using the M-hydrogel as a muscle fatigue sensor during exercise. A fully functional M-hydrogel is developed for real-time measurement of muscle fatigue during exercise and coupled it to a smartphone to provide a portable or wearable digital readout. This concept can be extended to other fields that require accurate analysis of constantly changing physical and chemical conditions, such as physiological changes in the human body.

Designing a next generation solar crystallizer for real seawater brine treatment with zero liquid discharge.

Proper disposal of industrial brine has been a critical environmental challenge. Zero liquid discharge (ZLD) brine treatment holds great promise to the brine disposal, but its application is limited by the intensive energy consumption of its crystallization process. Here we propose a new strategy that employs an advanced solar crystallizer coupled with a salt crystallization inhibitor to eliminate highly concentrated waste brine. The rationally designed solar crystallizer exhibited a high water evaporation rate of 2.42 kg m-2 h-1 under one sun illumination when treating real concentrated seawater reverse osmosis (SWRO) brine (21.6 wt%). The solar crystallizer array showed an even higher water evaporation rate of 48.0 kg m-2 per day in the outdoor field test, suggesting a great potential for practical application. The solar crystallizer design and the salt crystallization inhibition strategy proposed and confirmed in this work provide a low-cost and sustainable solution for industrial brine disposal with ZLD.

Skeletal screening IMPC/KOMP using µCT and computer automated cryohistology: Application to the Efna4 KO mouse line.

The IMPC/KOMP program provides the opportunity to screen mice harboring well defined gene-inactivation mutations in a uniform genetic background. The program performs a global tissue phenotyping survey that includes skeletal x-rays and bone density measurements. Because of the relative insensitivity of the two screening tests for detecting variance in bone architecture, we initiated a secondary screen based on µCT and a cryohistolomorphological workflow that was performed on the femur and vertebral compartments on 220 randomly selected knockouts (KOs) and 36 control bone samples over a 2 1/2 year collection period provided by one of the production/phenotyping centers. The performance of the screening protocol was designed to balance throughput and cost versus sensitivity and informativeness such that the output would be of value to the skeletal biology community. Here we report the reliability of this screening protocol to establish criteria for control skeletal variance at the architectural, dynamic and cellular histomorphometric level. Unexpected properties of the control population include unusually high variance in BV/TV in male femurs and greater bone formation and bone turnover rates in the female femur and vertebral trabeculae bone compartments. However, the manner for maintaining bone formation differed between these two bone sites. The vertebral compartment relies on maintaining a greater number of bone forming surfaces while the femoral compartment utilized more matrix production per cell. The comparison of the architectural properties obtained by µCT and histomorphology revealed significant differences in values for BV/TV, Tb.Th and Tb.N which is attributable to sampling density of the two methods. However, as a screening tool, expressing the ratio of KO to the control line as obtained by either method was remarkably similar. It identified KOs with significant variance which led to a more detailed histological analysis. Our findings are exemplified by the Efna4 KO, in which a high BV/TV was identified by µCT and confirmed by histomorphometry in the femur but not in the vertebral compartment. Dynamic labeling showed a marked increase in BFR which was attributable to increased labeling surfaces. Cellular analysis confirmed partitioning of osteoblast to labeling surfaces and a marked decrease in osteoclastic activity on both labeling and quiescent surfaces. This pattern of increased bone modeling would not be expected based on prior studies of the Ephrin-Ephrin receptor signaling pathways between osteoblasts and osteoclasts. Overall, our findings underscore why unbiased screening is needed because it can reveal unknown or unanticipated genes that impact skeletal variation.

Cryptotanshinone chemosensitivity potentiation by TW-37 in human oral cancer cell lines by targeting STAT3-Mcl-1 signaling.

BACKGROUND: Despite being one of the leading cancer types in the world, the diagnosis of oral cancer and its suitable therapeutic options remain limited. This study aims to investigate the single and chemosensitizing effects of TW-37, a BH3 mimetic in oral cancer, on human oral cancer cell lines. METHODS: We assessed the single and chemosensitizing effects of TW-37 in vitro using trypan blue exclusion assay, Western blotting, DAPI staining, Annexin V-FITC/PI double staining, and quantitative real-time PCR. Mcl-1 overexpression models were established by transforming vector and transient transfection was performed to test for apoptosis. RESULTS: TW-37 enhanced the cytotoxicity of human oral cancer cell lines by inducing caspase-dependent apoptosis, which correlates with the reduction of the myeloid cell leukemia-1 (Mcl-1) expression via transcriptional and post-translational regulation. The ectopic expression of Mcl-1 partially attenuated the apoptosis-inducing capacity of TW-37 in human oral cancer cell lines. Besides, TW-37 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and nuclear translocation in human oral cancer cell lines at the early time points. Furthermore, TW-37 potentiated chemosusceptibility of cryptotanshinone in human oral cancer cell lines by suppressing STAT3-Mcl-1 signaling compared with either TW-37 or cryptotanshinone alone, resulting in potent apoptosis. CONCLUSIONS: This study not only unravels the single and chemosensitizing effects of TW-37 for treatment of human oral cancer but also highlights the likelihood of TW-37 as a good therapeutic strategy to enhance the prognosis of patients with oral cancer in the future.

Photothermoelectric Response of Ti3C2Tx MXene Confined Ion Channels.

With recent growing interest in biomimetic smart nanochannels, a biological sensory transduction in response to external stimuli has been of particular interest in the development of biomimetic nanofluidic systems. Here we demonstrate the MXene-based subnanometer ion channels that convert external temperature changes to electric signals via preferential diffusion of cations under a thermal gradient. In particular, coupled with a photothermal conversion feature of MXenes, an array of the nanoconfined Ti3C2Tx ion channels can capture trans-nanochannel diffusion potentials under a light-driven axial temperature gradient. The nonisothermal open-circuit potential across channels is enhanced with increasing cationic permselectivity of confined channels, associated with the ionic concentration or pH of permeant fluids. The photothermoelectric ionic response (evaluated from the ionic Seebeck coefficient) reached up to 1 mV·K-1, which is comparable to biological thermosensory channels, and demonstrated stability and reproducibility in the absence and presence of an ionic concentration gradient. With advantages of physicochemical tunability and easy fabrication process, the lamellar ion conductors may be an important nanofluidic thermosensation platform possibly for biomimetic sensory systems.

Simultaneous production of fresh water and electricity via multistage solar photovoltaic membrane distillation.

The energy shortage and clean water scarcity are two key challenges for global sustainable development. Near half of the total global water withdrawals is consumed by power generation plants while water desalination consumes lots of electricity. Here, we demonstrate a photovoltaics-membrane distillation (PV-MD) device that can stably produce clean water (>1.64 kg·m-2·h-1) from seawater while simultaneously having uncompromised electricity generation performance (>11%) under one Sun irradiation. Its high clean water production rate is realized by constructing multi stage membrane distillation (MSMD) device at the backside of the solar cell to recycle the latent heat of water vapor condensation in each distillation stage. This composite device can significantly reduce capital investment costs by sharing the same land and the same mounting system and thus represents a potential possibility to transform an electricity power plant from otherwise a water consumer to a fresh water producer.

Astaxanthin attenuates the increase in mitochondrial respiration during the activation of hepatic stellate cells.

Upon liver injury, quiescent hepatic stellate cells (qHSCs) transdifferentiate to myofibroblast-like activated HSCs (aHSCs), which are primarily responsible for the accumulation of extracellular matrix proteins during the development of liver fibrosis. Therefore, aHSCs may exhibit different energy metabolism from that of qHSCs to meet their high energy demand. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, prevents the activation of HSCs. The objective of this study was to determine if ASTX can exert its antifibrogenic effect by attenuating any changes in energy metabolism during HSC activation. To characterize the energy metabolism of qHSCs and aHSCs, mouse primary HSCs were cultured on uncoated plastic dishes for 7 days for spontaneous activation in the presence or absence of 25 µM ASTX. qHSCs (1 day after isolation) and aHSCs treated with or without ASTX for 7 days were used to determine parameters related to mitochondrial respiration using a Seahorse XFe24 Extracellular Flux analyzer. aHSCs had significantly higher basal respiration, maximal respiration, ATP production, spare respiratory capacity and proton leak than those of qHSCs. However, ASTX prevented most of the changes occurring during HSC activation and improved mitochondrial cristae structure with decreased cristae junction width, lumen width and the area in primary mouse aHSCs. Furthermore, qHSCs isolated from ASTX-fed mice had lower mitochondrial respiration and glycolysis than control qHSCs. Our findings suggest that ASTX may exert its antifibrogenic effect by attenuating the changes in energy metabolism during HSC activation.

Two-Dimensional Ti3C2Tx MXene Membranes as Nanofluidic Osmotic Power Generators.

Salinity-gradient is emerging as one of the promising renewable energy sources but its energy conversion is severely limited by unsatisfactory performance of available semipermeable membranes. Recently, nanoconfined channels, as osmotic conduits, have shown superior energy conversion performance to conventional technologies. Here, ion selective nanochannels in lamellar Ti3C2Tx MXene membranes are reported for efficient osmotic power harvesting. These subnanometer channels in the Ti3C2Tx membranes enable cation-selective passage, assisted with tailored surface terminal groups, under salinity gradient. A record-high output power density of 21 W·m-2 at room temperature with an energy conversion efficiency of up to 40.6% is achieved by controlled surface charges at a 1000-fold salinity gradient. In addition, due to thermal regulation of surface charges and ionic mobility, the MXene membrane produces a large thermal enhancement at 331 K, yielding a power density of up to 54 W·m-2. The MXene lamellar structure, coupled with its scalability and chemical tunability, may be an important platform for high-performance osmotic power generators.

BioTarget: A Computational Framework Identifying Cancer Type Specific Transcriptional Targets of Immune Response Pathways.

Transcriptome data can provide information on signaling pathways active in cancers, but new computational tools are needed to more accurately quantify pathway activity and identify tissue-specific pathway features. We developed a computational method called "BioTarget" that incorporates ChIP-seq data into cellular pathway analysis. This tool relates the expression of transcription factor TF target genes (based on ChIP-seq data) with the status of upstream signaling components for an accurate quantification of pathway activity. This analysis also reveals TF targets expressed in specific contexts/tissues. We applied BioTarget to assess the activity of TBX21 and GATA3 pathways in cancers. TBX21 and GATA3 are TF regulators that control the differentiation of T cells into Th1 and Th2 helper cells that mediate cell-based and humoral immune responses, respectively. Since tumor immune responses can impact cancer progression, the significance of our pathway scores should be revealed by effective patient stratification. We found that low Th1/Th2 activity ratios were associated with a significantly poorer survival of stomach and breast cancer patients, whereas an unbalanced Th1/Th2 response was correlated with poorer survival of colon cancer patients. Lung adenocarcinoma and lung squamous cell carcinoma patients had the lowest survival rates when both Th1 and Th2 responses were high. Our method also identified context-specific target genes for TBX21 and GATA3. Applying the BioTarget tool to BCL6, a TF associated with germinal center lymphocytes, we observed that patients with an active BCL6 pathway had significantly improved survival for breast, colon, and stomach cancer. Our findings support the effectiveness of the BioTarget tool for transcriptome analysis and point to interesting associations between some immune-response pathways and cancer progression.