Syndrome Cell Adhesion Molecule Research Articles

Cognitive behavioral phenotyping of DSCAM heterozygosity as a model for autism spectrum disorder.

Autism spectrum disorder represents a growing patient population. Loss of one copy of the DSCAM gene provides a promising mouse model that reproduces autistic-like behaviors for research and therapeutic testing.

Cytoplasmic tail of transmembrane Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes of Chinese mitten crab (Eriocheir sinensis)

In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.

The role of Down syndrome cell adhesion molecule in Down syndrome.

Down syndrome (DS) is caused by the presence of an extra copy of the entire or a portion of human chromosome 21 (HSA21). This genomic alteration leads to elevated expression of numerous HSA21 genes, resulting in a variety of health issues in individuals with DS. Among the genes located in the DS "critical region" of HSA21, Down syndrome cell adhesion molecule (DSCAM) plays an important role in neuronal development. There is a growing body of evidence underscoring DSCAM's involvement in various DS-related disorders. This review aims to provide a concise overview ofthe established functions of DSCAM, with a particular focus on its implications in DS. We delve into the roles that DSCAM plays in DS-associated diseases. In the concluding section ofthis review, we explore prospective avenues for future research to further unravel DSCAM's role in DS and opportunities for therapeutic treatments.

Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation

In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission.

Memory consolidation in honey bees is enhanced by down-regulation of Down syndrome cell adhesion molecule and changes its alternative splicing.

Down syndrome cell adhesion molecule (Dscam) gene encodes a cell adhesion molecule required for neuronal wiring. A remarkable feature of arthropod Dscam is massive alternative splicing generating thousands of different isoforms from three variable clusters of alternative exons. Dscam expression and diversity arising from alternative splicing have been studied during development, but whether they exert functions in adult brains has not been determined. Here, using honey bees, we find that Dscam expression is critically linked to memory retention as reducing expression by RNAi enhances memory after reward learning in adult worker honey bees. Moreover, alternative splicing of Dscam is altered in all three variable clusters after learning. Since identical Dscam isoforms engage in homophilic interactions, these results suggest a mechanism to alter inclusion of variable exons during memory consolidation to modify neuronal connections for memory retention.

The rod synapse in aging wildtype and Dscaml1 mutant mice.

The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the rod circuit contribute to blinding diseases including retinitis pigmentosa and congenital stationary night blindness (CSNB). Down Syndrome cell adhesion molecule like 1 (Dscaml1) is expressed by rods, rod bipolar cells (RBCs), and sub-populations of amacrine cells, and has been linked to a middle age onset of CSNB in humans. However, how Dscaml1 contributes to this visual deficit remains unexplored. Here, we probed Dscaml1's role in the maintenance of the rod-to-RBC synapse using a loss of function mouse model. We used immunohistochemistry to investigate the anatomical formation and maintenance of the rod-to-RBC synapse in the young, adult, and aging retina. We generated 3D reconstructions, using serial electron micrographs, of rod spherules and RBCs to measure the number of invaginating neurites, RBC dendritic tip number, and RBC mitochondrial morphology. We find that while rod-to-RBC synapses form and are maintained, similar to wildtype, that there is an increase in the number of invaginating neurites in rod spherules, a reduction in RBC dendritic tips, and reduced mitochondrial volume and complexity in the Dscaml1 mutant retina compared to controls. We also observed precocious sprouting of RBC dendrites into the outer nuclear layer (ONL) of the Dscaml1 mutant retina compared to controls. These results contribute to our knowledge of Dscaml1's role in rod circuit development and maintenance and give additional insight into possible genetic therapy targets for blinding diseases and disorders like CSNB.

The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes.

Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21). Although several HSA21 genes have been found to be responsible for aspects of DS, whether and how HSA21 genes interact with each other is poorly understood. DS patients and animal models present with a number of neurological changes, including aberrant connectivity and neuronal morphology. Previous studies have indicated that amyloid precursor protein (APP) and Down syndrome cell adhesion molecule (DSCAM) regulate neuronal morphology and contribute to neuronal aberrations in DS. Here, we report the functional interaction between the Drosophila homologs of these two genes, Amyloid precursor protein-like (Appl) and Dscam (Dscam1). We show that Appl requires Dscam to promote axon terminal growth in sensory neurons. Moreover, Appl increases Dscam protein expression post-transcriptionally. We further demonstrate that regulation of Dscam by Appl does not require the Appl intracellular domain or second extracellular domain. This study presents an example of functional interactions between HSA21 genes, providing insights into the pathogenesis of neuronal aberrations in DS.

Immune functions of the Dscam extracellular variable region in Chinese mitten crab.

In arthropods, there is only a single copy of Down Syndrome Cell Adhesion Molecule (Dscam) in the genome, but it can exist as numerous splice variants. There are three hypervariable exons in the extracellular domain and one hypervariable exon in the transmembrane domain. In Chinese mitten crab (Eriocheir sinensis), exons 4, 6 and 14 can produce 25, 34 and 18 alternative splice variants, respectively. In this study, through Illumina sequencing, we identified additional splice variants for exons 6 and 14, hence there may be>50,000 Dscam protein variants. Sequencing of exons 4, 6 and 14 showed that alternative splicing was altered after bacterial stimulation. Therefore, we expressed and purified the extracellular variable region of Dscam (EsDscam-Ig1-Ig7). Exons 4.3, 6.46 and 14.18, three variable exons of the recombinant protein, were randomly selected. The functions of EsDscam-Ig1-Ig7 in immune defences of E. sinensis were subsequently explored. EsDscam-Ig1-Ig7 was discovered to bind to both Gram-positive Staphylococcus aureus and Gram-negative Vibrio parahaemolyticus, but it did not exhibit antibacterial activity. By promoting hemocyte phagocytosis and bacterial removal, EsDscam-Ig1-Ig7 can also shield the host from bacterial infection. The findings highlight the immunological activities of Dscam alternative splicing and reveal the potential for many more Dscam isoforms than were previously predicted in E. sinensis.

Changes in working memory induced by lipopolysaccharide administration in mice are associated with metabotropic glutamate receptors 5 and contrast with changes induced by cyclooxygenase-2: Involvement of postsynaptic density protein 95 and down syndrome cell adhesion molecule

The strength and quality of the signal propagated by the glutamate synapse (Glu) depend, among other things, on the structure of the postsynaptic part and the quality of adhesion between the interacting components of the synapse. Postsynaptic density protein 95 (PSD95), mammalian target of rapamycin (mTOR), and Down syndrome cell adhesion molecule (DSCAM) are components of the proper functioning of an excitatory synapse. PSD95 is a member of the membrane-associated guanylate kinases protein family, mainly located at the postsynaptic density of the excitatory synapse. PSD95, via direct interaction, regulates the clustering and functionality of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors at a synapse. Here, the effects of treatment with an antagonist of mGluR5 (MTEP) and NS398 (cyclooxygenase-2, COX-2 inhibitor) on PSD95, mTOR, and DSCAM in the hippocampus (HC) of C57B1/6 J mice using Western blots in the context of learning were examined. Moreover, the sensitivity of selected proteins to lipopolysaccharide (LPS) was monitored. MTEP injected for seven days induced upregulation of PSD95 in HC of mice. The observed effect was regulated by a COX-2 inhibitor and concurrently by LPS. Accompanying alterations in DSCAM protein were found, suggesting changes in adhesion strength after modulation of glutamatergic (Glu) synapse via tested compounds.

DSCAM gene triplication causes excessive GABAergic synapses in the neocortex in Down syndrome mouse models.

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders.

Cis mutagenesis in vivo reveals extensive noncanonical functions of Dscam1 isoforms in neuronal wiring.

Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) encodes tens of thousands of cell recognition molecules via alternative splicing, which are required for neural function. A canonical self-avoidance model seems to provide a central mechanistic basis for Dscam1 functions in neuronal wiring. Here, we reveal extensive noncanonical functions of Dscam1 isoforms in neuronal wiring. We generated a series of allelic cis mutations in Dscam1, encoding a normal number of isoforms, but with an altered isoform composition. Despite normal dendritic self-avoidance and self-/nonself-discrimination in dendritic arborization (da) neurons, which is consistent with the canonical self-avoidance model, these mutants exhibited strikingly distinct spectra of phenotypic defects in the three types of neurons: up to ∼60% defects in mushroom bodies, a significant increase in branching and growth in da neurons, and mild axonal branching defects in mechanosensory neurons. Remarkably, the altered isoform composition resulted in increased dendrite growth yet inhibited axon growth. Moreover, reducing Dscam1 dosage exacerbated axonal defects in mushroom bodies and mechanosensory neurons but reverted dendritic branching and growth defects in da neurons. This splicing-tuned regulation strategy suggests that axon and dendrite growth in diverse neurons cell-autonomously require Dscam1 isoform composition. These findings provide important insights into the functions of Dscam1 isoforms in neuronal wiring.

Cherax quadricarinatus Resistant to Chequa iflavirus: A Pilot Study.

High mortalities of redclaw crayfish (Cherax quadricarinatus) were reported from northern Queensland farms, mainly attributed to two viruses, Chequa iflavirus and Athtab bunyavirus. From a research population of redclaw crayfish with these pre-existing viral infections, five individuals were found uninfected by Chequa iflavirus but infected with Athtab bunyavirus. A pilot study was designed to examine if progeny crayfish from this cohort were resistant to infections by Chequa iflavirus. Two experiments measured changes in viral load with RT-qPCR. Seven donors, four negative controls and six crayfish injected with a purified virus or saline were used. In Experiment 1, the purified viral inoculum was injected into the crayfish, and they were bled 14 days post-injection (dpi). In Experiment 2, haemolymph containing the viruses was injected into the same crayfish and they were bled at 24 hpi, 48 hpi, 7 dpi and 14 dpi. In Exp. 1, the crayfish cleared Chequa iflavirus infections within 14 dpi, while in Exp. 2, it was within 24 hpi. One mortality was observed, but that crayfish had cleared the virus before dying. The number of copies of Athtab bunyavirus and the weights of the crayfish did not differ significantly (p > 0.05) between the control and injected crayfish. Histology of crayfish all showed that the haemolymph vessels were clear of granulomas, suggesting no bacterial involvement. There was no melanisation in the gill tissue of control crayfish, but it was prominent in virus-injected crayfish. Neither group had haemocytic infiltration of the muscle fibres. Anti-viral immune mechanisms of RNA interference and Cherax quadricarinatus Down Syndrome Cell Adhesion Molecule (DSCAM) are hypothesised to be involved in viral clearance. We conclude that these crayfish were resistant to Chequa iflavirus infections and could be commercially exploited by aquaculturists as a nuclear breeding stock if numbers are increased over time.

Extracellular vesicle signatures and protein citrullination are modified in shore crabs (Carcinus maenas) infected with Hematodinium sp

ABSTRACT Epizootiologists recurrently encounter symbionts and pathobionts in the haemolymph (blood equivalent) of shellfish. One such group is the dinoflagellate genus Hematodinium, which contains several species that cause debilitating disease in decapod crustaceans. The shore crab Carcinus maenas acts as a mobile reservoir of microparasites, including Hematodinium sp., thereby posing a risk to other co-located commercially important species, e.g. velvet crabs (Necora puber). Despite the widespread prevalence and documented seasonality of Hematodinium infection dynamics, there is a knowledge gap regarding host-pathogen antibiosis, namely, how Hematodinium avoids the host’s immune defences. Herein, we interrogated the haemolymph of Hematodinium-positive and Hematodinium-negative crabs for extracellular vesicle (EV) profiles (a proxy for cellular communication), alongside proteomic signatures for post-translational citrullination/deimination performed by arginine deiminases, which can infer a pathologic state. Circulating EV numbers in parasitized crab haemolymph were reduced significantly, accompanied by smaller EV modal size profiles (albeit non-significantly) when compared to Hematodinium-negative controls. Differences were observed for citrullinated/deiminated target proteins in the haemolymph between the parasitized and control crabs, with fewer hits identified overall in the former. Three deiminated proteins specific to parasitized crab haemolymph were actin, Down syndrome cell adhesion molecule (DSCAM), and nitric oxide synthase – factors that contribute to innate immunity. We report, for the first time, Hematodinium sp. could interfere with EV biogenesis, and that protein deimination is a putative mechanism of immune-modulation in crustacean-Hematodinium interactions.

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function.

The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in zebrafish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1-linked neuropsychiatric disorders.

Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer

BackgroundA preoperative-progesterone intervention increases disease-free survival in patients with breast cancer, with an unknown underlying mechanism. We elucidated the role of non-coding RNAs in response to progesterone in human breast cancer.MethodsWhole transcriptome sequencing dataset of 30 breast primary tumors (10 tumors exposed to hydroxyprogesterone and 20 tumors as control) were re-analyzed to identify differentially expressed non-coding RNAs followed by real-time PCR analyses to validate the expression of candidates. Functional analyses were performed by genetic knockdown, biochemical, and cell-based assays.ResultsWe identified a significant downregulation in the expression of a long non-coding RNA, Down syndrome cell adhesion molecule antisense DSCAM-AS1, in response to progesterone treatment in breast cancer. The progesterone-induced expression of DSCAM-AS1 could be effectively blocked by the knockdown of progesterone receptor (PR) or treatment of cells with mifepristone (PR-antagonist). We further show that knockdown of DSCAM-AS1 mimics the effect of progesterone in impeding cell migration and invasion in PR-positive breast cancer cells, while its overexpression shows an opposite effect. Additionally, DSCAM-AS1 sponges the activity of miR-130a that regulates the expression of ESR1 by binding to its 3’-UTR to mediate the effect of progesterone in breast cancer cells. Consistent with our findings, TCGA analysis suggests that high levels of miR-130a correlate with a tendency toward better overall survival in patients with breast cancer.ConclusionThis study presents a mechanism involving the DSCAM-AS1/miR-130a/ESR1 genomic axis through which progesterone impedes breast cancer cell invasion and migration. The findings highlight the utility of progesterone treatment in impeding metastasis and improving survival outcomes in patients with breast cancer.

Alternatively spliced exon 33 in Dscam controls antibacterial responses through regulating cellular endocytosis and regulation of actin cytoskeleton gene expression in the hemocytes of the Chinese mitten crab (Eriocheir sinensis)

It has been widely established that Down syndrome cell adhesion molecule (Dscam) regulates arthropod cellular endocytosis. However, the signal transduction pathways and molecular mechanisms of the regulatory process remain unclear. Our previous study identified a Dscam-mediated immune signal transduction pathway that regulates cellular antimicrobial peptide expression, and a conserved endocytosis motif encoded by exon 33 in the cytoplasmic tail of transmembrane Dscam. Therefore, the present study aimed to determine the transcriptional response of the Chinese mitten crab (Eriocheir sinensis) Dscam with a cytoplasmic tail encoded by different exons. In the group of exon 32 knockdown, 306 differentially expressed genes (DEGs) were identified, and 3579 differentially expressed genes (DEGs) were identified in the group of exon 33 knockdown (green fluorescent protein, (GFP) as control). The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. Quantitative real-time reverse transcription PCR validated the data for selected genes. Our study contributes to the understanding of the immune defense mechanism in E. sinensis and the development of the innate immune system, thus providing insights into disease control and prevention in aquaculture.

Dscam1 overexpression impairs the function of the gut nervous system in Drosophila.

Down syndrome (DS) patients have a 100-fold increase in the risk of Hirschsprung syndrome of the colon and rectum (HSCR), a lack of enteric neurons in the colon. The leading DS candidate gene is trisomy of the Down syndrome cell adhesion molecule (DSCAM). We find that Dscam1 protein is expressed in the Drosophila enteric/stomatogastric nervous system (SNS). Axonal Dscam1 phenotypes can be rescued equally by diverse isoforms. Overexpression of Dscam1 resulted in frontal and hindgut nerve overgrowth. Expression of dominant negative Dscam1-ΔC led to a truncated frontal nerve and increased branching of the hindgut nerve. Larval locomotion is influenced by feeding state, and we found that the average speed of larvae with Dscam1 SNS expression was reduced, whereas overexpression of Dscam1-ΔC significantly increased the speed. Dscam1 overexpression reduced the efficiency of food clearance from the larval gut. Our work demonstrates that overexpression of Dscam1 can perturb gut function in a model system.

Induction and potential molecular mechanism of the enhanced immune response in Procambarus clarkii after secondary encountered with Aeromonas veronii

For a long time, it was believed that invertebrates do not possess acquired immunity and mainly rely on innate immunity for protection against pathogens infection. However, an increasing number of studies have suggested that some form of “immune memory” can be initiated in invertebrates after primary exposure to the pathogen, which was defined as “specific immune priming”. In the present study, two experiments were carried out to determine whether specific immune priming can be induced in crayfish (Procambarus clarkii) by Aeromonas veronii, if so, to identify the underlying mechanism. Once being “preimmunization” by formalin-killed A. veronii, the survival rate, in vitro antibacterial activity and haemocyte phagocytosis rate of crayfish were enhanced, which indicated that better immune protection was obtained. Furthermore, at some time points, the expression of antimicrobial peptide (AMP) and Down syndrome cell adhesion molecule (Dscam) genes was significantly higher in P. clarkii individuals that underwent stimulation twice than in those that were only stimulated once. Taken together, the results suggest that enhanced specific immune protection can be obtained in primed crayfish and that the Dscam molecule, haemocyte phagocytosis function, and AMPs may be involved in this immune priming. The present study provides a better understanding of the molecular mechanism of immune priming in invertebrates.

Comparative transcriptomics reveals the immune dynamics during the molting cycle of swimming crab Portunus trituberculatus.

Molting is one of the most important biological processes of crustacean species, and a number of molecular mechanisms facilitate this complex procedure. However, the understanding of the immune mechanisms underlying crustacean molting cycle remains very limited. This study performed transcriptome sequencing in hemolymph and hepatopancreas of the swimming crab (Portunus trituberculatus) during the four molting stages: post-molt (AB), inter-molt (C), pre-molt (D), and ecdysis (E). The results showed that there were 78,572 unigenes that were obtained in the hemolymph and hepatopancreas of P. trituberculatus. Further analysis showed that 98 DEGs were involved in immunity response of hemolymph and hepatopancreas, and most of the DEGs participated in the process of signal transduction, pattern recognition proteins/receptors, and antioxidative enzymes system. Specifically, the key genes and pathway involved in signal transduction including the GPCR126, beta-integrin, integrin, three genes in mitogen-activated protein kinase (MAPK) signaling cascade (MAPKKK10, MAPKK4, and p38 MAPK), and four genes in Toll pathway (Toll-like receptor, cactus, pelle-like kinase, and NFIL3). For the pattern recognition proteins/receptors, the lowest expression level of 11 genes was found in the E stage, including C-type lectin receptor, C-type lectin domain family 6 member A and SRB3/C in the hemolymph, and hepatopancreatic lectin 4, C-type lectin, SRB, Down syndrome cell adhesion molecule homolog, Down syndrome cell adhesion molecule isoform, and A2M. Moreover, the expression level of copper/zinc superoxide dismutase isoform 4, glutathione peroxidase, glutathione S-transferase, peroxiredoxin, peroxiredoxin 6, and dual oxidase 2 in stage C or stage D significantly higher than that of stage E or stage AB. These results fill in the gap of the continuous transcriptional changes that are evident during the molting cycle of crab and further provided valuable information for elucidating the molecular mechanisms of immune regulation during the molting cycle of crab.

Construction of a multiple-class classifier based on mRNAs and lncRNA FAM66A and PSORS1C3 for predicting distant metastasis in lung adenocarcinoma.

There are several mechanisms believed to be essential for the development of distant metastasis in lung adenocarcinoma (LUAD), but the prediction of distant metastasis is still a challenge. The purpose of the present study was to examine the specific changes in RNA expression, including long non-coding RNAs (lncRNAs) in distant metastasis patients. We compared differentially expressed genes involved in distant metastasis from otherwise non-metastasis and healthy adults using a gene expression profile. We first ranked gene sets (or gene signatures) that identify each class. An advanced multiple-class classifier was built based on the gene sets. Our classifier consisted of 282 genes and could predict cancer and distant metastasis with error rates of approximately 0.01 and 0.2, respectively. Then, gene networks were built to undermine gene relations to each class. Cytochrome P450 family 4 subfamily F member 12 (CYP4F12) was the first gene in the ranking of the distant metastasis case. Down syndrome cell adhesion molecule (DSCAM) was the top gene in the rank list of the non-metastasis case. Solute carrier family 6 member 4 (SLC6A4) was associated with normal tissues. LncRNA family with sequence similarity 66 member A (FAM66A) and lncRNA PSORS1C3 were found to be associated with tumor metastasis. Our classifier could successfully predict distant metastasis in LUAD patients. LncRNA FAM66A and lncRNA PSORS1C3 in our model could play a role in cancer development.