Periodontitis is an oral immunoinflammatory disease induced by bacterial infection. During periodontitis, the aggravating destruction of the alveolar bone can result in tooth movement and even tooth loss. Current conventional treatments for periodontitis primarily focus on infection control, but their effectiveness in halting and restoring alveolar bone destruction is limited. To identify additional therapeutic targets, researchers have been dedicated to investigating other pathological mechanisms underlying alveolar bone loss during periodontitis. Recently, findings indicate that ferroptosis plays a role in the development of periodontitis. Ferroptosis is a nonapoptotic type of cell death marked by iron accumulation and lipid peroxidation. Recent investigations have revealed the complex interplay of ferroptosis and inflammation. The positive feedback loop between ferroptosis and inflammation may significantly contribute to the exacerbation of alveolar bone loss. In light of the advancements in research within this field in recent years, this review intends to thoroughly summarize the processes by which ferroptosis aggravates alveolar bone loss during periodontitis, along with relevant ferroptosis-targeted therapeutic agents. By highlighting the latest advancements in this area, we hope this review will inspire researchers to develop novel therapeutic strategies for more effective inflammation control and regeneration of alveolar bone.

Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host-microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.

Aldehydes are molecules that are commonly found in both human physiology and the environment. The accumulation of these substances can lead to the cross-linking of intracellular DNA and proteins, thereby disrupting cellular function and contributing to the processes of premature aging and age-related diseases. Aldehyde dehydrogenase 2 (ALDH2), the key member of ALDH family, is an enzyme responsible for aldehyde metabolism, composed of four identical subunits located within the mitochondrial matrix. Its primary role is to catalyze the oxidation of aldehydes, resulting in the formation of their corresponding acid metabolites. This paper presents a succinct overview of the sources and metabolic pathways of key aldehydes within the human body, compares the various primary enzymes involved in aldehyde metabolism, and explores the structural and functional characteristics of ALDH2. Furthermore, ALDH2 is proposed as a potential therapeutic target for addressing aging and associated diseases. The discussion also includes prospective research avenues, particularly focusing on ALDH2 agonists and aldehyde scavengers designed to enhance the clearance of reactive aldehydes and safeguard cellular functions, thereby mitigating aldehyde-induced cellular damage and potentially delaying the aging process.

Biochemical recurrence (BCR) following radical prostatectomy (RP) remains a major challenge in prostate cancer (PCa) management. Tryptophan metabolism plays a pivotal role in tumor progression and immune modulation. This study aimed to develop and validate a tryptophan metabolism-related risk model and molecular subtypes to predict BCR in PCa patients after RP.

The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset, including 421 PCa patients, was analyzed to identify key tryptophan metabolism-related genes (TMRGs) using differential expression, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) regression analyses. The tryptophan metabolism-related risk model was constructed through multivariate Cox regression, and tryptophan metabolism-related molecular subtypes were established using consensus clustering. External validation was conducted using an independent dataset, while immunohistochemistry (IHC) and single-cell sequencing further confirmed TMRG expression patterns and their roles in the tumor microenvironment (TME).

The tryptophan metabolism-related risk model and molecular subtypes effectively stratified PCa patients into low- and high-risk groups or two molecular subtypes. High-risk PCa patients (n=211) and those in Cluster 1 (n=261) exhibited significantly poorer biochemical recurrence-free survival (BRFS) and distinct clinicopathological features, immune infiltration profiles, and TME characteristics. External validation confirmed the robustness of the tryptophan metabolism-related risk model and molecular subtypes. IHC and single-cell sequencing highlighted the expression patterns of TMRGs and their regulatory roles in the TME.

This study established and validated tryptophan metabolism-related risk scores and molecular subtypes as reliable predictors of BCR in PCa patients after RP. These findings provide a foundation for personalized follow-up and treatment strategies, contributing to improved clinical outcomes in PCa management.

The nervous system plays an important role in regulating physiological functions of the stomach, and its abnormal activity often impairs gastric homeostasis. In response to constant exposure to oncogenic stimuli that leads to gastric tumorigenesis, the neural system becomes an essential component of the tumor microenvironment via perineural infiltration, de novo neurogenesis, and axonogenesis, thereby driving cancer initiation and progression. In this review, we highlight emerging discoveries related to neural-cancer crosstalk and discuss how the nervous system is remodeled by tumor cells including neural components and modulators (including neurotransmitters and neuropeptides). Moreover, we provide a systematic analysis of neural control of the cellular hallmarks of cancer. Finally, we propose how the molecular circuits of neural-cancer crosstalk could be exploited as potential targets for novel anti-cancer treatment, providing new insights into a new modality of neural-based cancer therapeutic strategies.

Cancer incidence and mortality are lower among high-altitude residents, suggesting that hypobaric hypoxia (HH) might protect against cancer. Our study aimed to develop a pan-cancer prognosis risk model using ADME genes, which are influenced by low oxygen, to explore HH's impact on overall survival (OS) across various cancers. We constructed and validated the model with gene expression and survival data from 8628 samples, using three gene expression databases. AltitudeOmics confirmed HH's significant effects. We employed single-gene prognostic analysis, weighted gene co-expression network analysis, and stepwise Cox regression to identify biomarkers and refine the model. Drugs interacting with the model were explored using LINCS L1000, AutoDockTools, and STITCH. Eight ADME genes significantly altered by HH were identified, revealing their prognostic value across cancers. The model showed lower risk scores linked to better prognosis in 25 cancers, with reduced overall gene expression and decreased tumor mortality risk. Higher T cell infiltration was observed in the low-risk group. Additionally, three potential drugs to modulate our model were identified. This study presents a novel pan-cancer survival prognosis model based on ADME genes influenced by HH, offering new insights into cancer prevention and treatment.

The aim of the current study was to investigate the relationship between environmental factors and metabolic gene genotypes related to semen quality.

A total of 341 men were recruited and classified into normal or abnormal semen quality groups according to the World Health Organization's 2010 criteria. Alcohol and tobacco use among men was self-reported. Pb (lead), As (arsenic), Ti (titanium), and Zn (zinc) metal elements in seminal plasma were measured using inductively coupled plasma mass spectrometry (ICP-MS). The ALDH2 rs671 and GSTP1 rs1695 polymorphism were detected using high-resolution melting (HRM) PCR.

Individual environmental factors, including smoking, drinking, and exposure to Pb, As, Ti, or Zn, did not significantly associate with the risk of semen abnormalities. The ALDH2 GA/AA mutation genotype increased the risk of semen abnormalities in smoking males (AOR = 1.27; 95% CI, 1.01-1.62) and in males with high seminal Ti levels (AOR = 1.36; 95% CI, 1.00-1.90). The GSTP1 rs1695 gene (GG/AG) mutation genotype exhibited a protective effect on semen quality in males who did not consume alcohol (AOR = 0.65; 95% CI, 0.51-0.85) or smoke (AOR = 0.79; 95% CI, 0.61-1.00), as well as in those with low Pb (AOR = 0.63; 95% CI, 0.46-0.88) and Ti (AOR = 0.64; 95% CI, 0.47-0.90) exposure.

The current study demonstrated that genetic and environmental factors interact with semen quality, and that men with the ALDH2 rs671A or GSTP1 rs1695A allele are susceptible to Ti-, alcohol-, and tobacco-induced semen quality abnormalities.

The incidence of lung adenocarcinoma (LAD) is increasing worldwide. Single-nucleotide polymorphisms in aldehyde dehydrogenase 2 family member gene ( ALDH2 ) rs671 and alcohol dehydrogenase 1B ( ADH1B ) rs1229984 are common and functionally important genetic variants to metabolize endogenous and exogenous aldehyde chemicals, related to cancer.

This is a case-control study. A total of 150 newly diagnosed LAD patients were from Kaohsiung Medical University Hospital, Taiwan, between 2019 and 2022. Two control groups, TWB-1 ( n  = 600) and TWB-2 ( n  = 29 683), were selected from Taiwan Biobank (TWB), and the case patients were frequency-matched with TWB-1 based on age category (30-60 or >60 years old), sex, and education levels. Logistic regression models were employed to analyze the association between two genetic variants and LAD risk.

A significant association was noted between ALDH2 and LAD risk. Those with ALDH2 rs671 *2/*2 in TWB-1 and TWB-2 controls had a 2.68-fold (95% CI = 1.43-4.99) and a 1.83-fold (95% CI = 1.07-3.11) increased risk of LAD, respectively, compared with those with ALDH2 rs671 *1/*1 or *1/*2 , after adjusting for covariates. This association was particularly pronounced in females. No overall significant association between ADH1B rs1229984 and LAD risk was observed.

The findings indicate a strong and robust risk association between ALDH2 rs671*2/*2 and LAD in the Taiwan population, particularly in Taiwanese female adults.

Catabolic metabolites of tryptophan (Trp) are considered to be important microenvironmental factors by suppressing anti-tumor immune responses in cancers. Nevertheless, the effect of Trp metabolism (Trp metabolism)-related genes Trp metabolism-related genes on laryngeal squamous cell carcinoma (LSCC) progression is not yet clear. So, in this study, the TCGA-LSCC, GSE27020, and 40 TMRGs were extracted via public databases to explore the effects of TMRGs on laryngeal squamous cell carcinoma. Firstly, Weighted Gene Co-expression Network Analysis (WGCNA) was adopted with LSCC samples in TCGA-LSCC to acquire key module, and differentially expressed genes between LSCC and normal samples from TCGA-LSCC were yielded via differential expression analysis. Next, differentially expressed TMRGs (DE-TMRGs) was obtained in key model and DEGs, and prognostic genes were identifde through multiple algorithms. Five prognostic genes, namely SERPINA1, TMC8, RENBP, SDS and FAM107A were finally identified. A risk model was established based on the expressions of prognostic genes and survival information of LSCC samples while that were divided into high and low risk groups. Obviously, the LSCC immune dysfunction and exclusion score of high-risk patients was dramatically higher than that in low-risk patients, indicating that patients in the high-risk subgroup exhibited reduced responsiveness to immunotherapy. Besides, the drug sensitivity analysis showed that the low -risk subgroup was notably sensitive to Salubrinal, Lenalidomide, Metformin, while high -risk subgroup was more responsive to Docetaxel, AUY922, Embelin. Eventually, two clusters of LSCC samples had notable correlations with LSCC prognosis. The above results indicated that the risk model consisted of TMRGs (SERPINA1, TMC8, RENBP, SDS and FAM107A) was constructed in LSCC, contributing to studies related to the prognosis and treatment of LSCC.

The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.

We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD).

Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial-mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD.

A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.

Spermatogenesis and sperm maturation are complex biological processes that involve intricate cellular and molecular interactions. The Aldh2 gene is involved in the metabolism of specific aldehydes generated by oxidative stress. Aldh2 is abundantly expressed in the testis and epididymis; however, the specific role of Aldh2 in regulating spermatogenesis and sperm maturation remains unclear. In the present study, we generated Aldh2 knockout (Aldh2-/-) mice by using CRISPR/Cas9 technology. Aldh2 gene knockout decreased the fertility of male mice. Compared to the control group mice, Aldh2-/- mice showed a significant decrease in the thickness of the seminiferous tubules and the number of germ cells. Further investigation revealed that the meiosis of spermatocytes and acrosome formation in sperm were disrupted in Aldh2-/- mice, leading to oligoasthenoteratozoospermia in male mice. However, the caput epididymis and cauda epididymis in Aldh2-/- mice showed identical proportions of morphologically abnormal sperm. Mechanistically, 4-hydroxynonenal, 3-nitro-L-tyrosine, and malondialdehyde levels were significantly elevated in both the testis and epididymis of Aldh2-/- mice, thus indicating increased oxidative stress in the reproductive system. Collectively, our findings demonstrate that Aldh2 plays a critical role in spermatogenesis by regulating oxidative stress in mice.

The mechanisms underlying the complex relationship between autoimmune hypothyroidism and neurological disorders remain unclear. We conducted a comprehensive analysis of associations between alternative splicing, transcriptomics, and proteomics data and autoimmune hypothyroidism.

Splicing-wide association studies (SWAS), proteome-wide association studies (PWAS), and transcriptome-wide association studies (TWAS) were used to identify genes and proteins that regulate autoimmune hypothyroidism within the brain axis. We performed TWAS on GTEx V8 thyroid tissue data to identify autoimmune hypothyroidism-associated thyroid axis genes. A FUSION analysis of overlapping genes in the brain and thyroid axes and brain splicing weights was conducted to determine the influence of alternative splicing in the brain on thyroid tissue gene expression.

SWAS identified 223 alternative splicing events, TWAS identified 270 genes, and PWAS revealed five genes (FDPS, PPIL3, PEX6, MMAB, and ALDH2) encoding proteins associated with autoimmune hypothyroidism. Neuroimaging analyses revealed distinct brain-imaging phenotypes associated with these five genes. TWAS of thyroid tissue identified four genes (FDPS, PPIL3, MMAB, and ALDH2) associated with the brain axis related to thyroid tissue. A FUSION analysis indicated that alternative splicing changes in ALDH2 in brain tissue influenced its expression in thyroid tissue.

Integrating brain splicing, proteomic, and transcriptomic data supports the association between specific genes and proteins in the brain and autoimmune hypothyroidism. Additionally, ALDH2 alternative splicing in brain tissue influences its thyroid tissue expression. These findings provide new insights into the molecular basis of autoimmune hypothyroidism, facilitating future pathogenesis research.

Necroptosis, a recently identified mechanism of programmed cell death, exerts significant influence on various aspects of cancer biology, including tumor cell proliferation, stemness, metastasis, and immunosuppression. However, the role of necroptosis-related genes (NRGs) in Hepatocellular Carcinoma (HCC) remains elusive.

In this study, we assessed the mutation signature, copy number variation, and expression of 37 NRGs in HCC using the TCGA-LIHC dataset. We further validated our results using the ICGC-LIRI-JP dataset. To construct our prognostic model, we utilized the least absolute shrinkage and selection operator (LASSO), and evaluated the predictive efficacy of the NRGs-score using various machine learning algorithms, including K-M curves, time-ROC curves, univariate and multivariate Cox regression, and nomogram. In addition, we analyzed immune infiltration using the CIBERSOFT and ssGSEA algorithms, calculated the stemness index through the one-class logistic regression (OCLR) algorithm, and performed anti-cancer stem cells (CSCs) drug sensitivity analysis using oncoPredict. Finally, we validated the expression of the prognostic NRGs through qPCR both in vitro and in vivo.

About 18 out of 37 NRGs were found to be differentially expressed in HCC and correlated with clinical outcomes. To construct a prognostic model, six signature genes (ALDH2, EZH2, PGAM5, PLK1, SQSTM1, and TARDBP) were selected using LASSO analysis. These genes were then employed to categorize HCC patients into two subgroups based on NRGs-score (low vs. high). A high NRGs score was associated with a worse prognosis. Furthermore, univariate and multivariate Cox regression analyses were performed to confirm the NRGs-score as an independent risk factor. These analyses revealed strong associations between NRGs-score and critical factors, such as AFP, disease stage, and tumor grade in the HCC cohort. NRGs-score effectively predicted the 1-, 3-, and 5-year survival of HCC patients. Immune infiltration analysis further revealed that the expression of immune checkpoint molecules was significantly enhanced in the high NRGs-score group. Stemness analysis in the HCC cohort showed that NRGs-score was positively correlated with mRNA stemness index, and patients with high NRGs-score were sensitive to CSCs inhibitors. The findings from the external validation cohort provided confirmation that the NRGs-score presented a trait with universal applicability in accurately predicting the survival of HCC. Additionally, the six prognostic genes were consistently differentially expressed in both the HCC cell line and the mouse HCC model.

Our study demonstrated the pivotal role of NRGs in promoting stemness and immune suppression in HCC and established a robust model which could successfully predict HCC prognosis.

Studies have shown that tumor cell amino acid metabolism is closely associated with lung adenocarcinoma (LUAD) development and progression. However, the comprehensive multi-omics features and clinical impact of the expression of genes associated with amino acid metabolism in the LUAD tumor microenvironment (TME) are yet to be fully understood.

LUAD patients from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort. Using least absolute shrinkage and selection operator Cox regression analysis, we developed PTAAMG-Sig, a signature based on the expression of tumor-specific amino acid metabolism genes associated with overall survival (OS) prognosis. We evaluated its predictive performance for OS and thoroughly explored the effects of the PTAAMG-Sig risk score on the TME. The risk score was validated in two Gene Expression Omnibus (GEO) cohorts and further investigated against an original cohort of chemotherapy combined with immune checkpoint inhibitors (ICIs). Somatic mutation, chemotherapy response, immunotherapy response, gene set variation, gene set enrichment, immune infiltration, and plasma-free amino acids (PFAAs) profile analyses were performed to identify the underlying multi-omics features.

TCGA datasets based PTAAMG-Sig model consisting of nine genes, KYNU, PSPH, PPAT, MIF, GCLC, ACAD8, TYRP1, ALDH2, and HDC, could effectively stratify the OS in LUAD patients. The two other GEO-independent datasets validated the robust predictive power of PTAAMG-Sig. Our differential analysis of somatic mutations in the high- and low-risk groups in TCGA cohort showed that the TP53 mutation rate was significantly higher in the high-risk group and negatively correlated with OS. Prediction from transcriptome data raised the possibility that PTAAMG-Sig could predict the response to chemotherapy and ICIs therapy. Our immunotherapy cohort confirmed the predictive ability of PTAAMG-Sig in the clinical response to ICIs therapy, which correlated with the infiltration of immune cells (e.g., T lymphocytes and nature killer cells). Corresponding to the concentrations of PFAAs, we discovered that the high PTAAMG-Sig risk score patients showed a significantly lower concentration of plasma-free α-aminobutyric acid.

In patients with LUAD, the PTAAMG-Sig effectively predicted OS, drug sensitivity, and immunotherapy outcomes. These findings are expected to provide new targets and strategies for personalized treatment of LUAD patients.

Tumor, as the second leading cause of death globally, following closely behind cardiovascular diseases, remains a significant health challenge worldwide. Despite the existence of various cancer treatment methods, their efficacy is still suboptimal, necessitating the development of safer and more efficient treatment strategies. Additionally, the advancement of personalized therapy offers further possibilities in cancer treatment. Nanomedicine, as a promising interdisciplinary field, has shown tremendous potential and prospects in the diagnosis and treatment of cancer. As an emerging approach in oncology, the application of nanomedicine in personalized cancer therapy primarily focuses on targeted drug delivery systems such as passive targeting drug delivery, active targeting drug delivery, and environmentally responsive targeting drug delivery, as well as imaging diagnostics such as tumor biomarker detection, tumor cell detection, and in vivo imaging. However, it still faces challenges regarding safety, biocompatibility, and other issues. This review aims to explore the advances in the use of nanomaterials in the field of personalized cancer diagnosis and treatment and to investigate the prospects and challenges of developing personalized therapies in cancer care, providing direction for the clinical translation and application.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme primarily involved in the detoxification of alcohol-derived aldehyde and endogenous toxic aldehydes. It exhibits widespread expression across various organs and exerts a broad and significant impact on diverse acute cardiovascular diseases, including acute coronary syndrome, acute aortic dissection, hypoxic pulmonary hypertension, and heart failure. The ALDH2 rs671 variant represents the most prevalent genetic variant in East Asian populations, with carriage rates ranging from 30 to 50% among the Chinese population. Given its widespread presence in the body, the wide range of diseases it affects, and its high rate of variation, it can serve as a crucial tool for the precise prevention and treatment of acute cardiovascular diseases, while offering individualized medication guidance. This review aims to provide a comprehensive overview of the latest advancements in factors affecting ALDH2 activity, encompassing post-transcriptional modifications, modulators of ALDH2, and relevant clinical drugs.

Ferroptosis is a regulated cell death driven by iron-dependent lipid peroxidation and associated with drug resistance in lung adenocarcinoma (LUAD). It's found that aldehyde dehydrogenase 2 (ALDH2), which is highly mutated in East Asian populations, is correlated with response to chemotherapy in LUAD patients. The rs671 variant knock-in, downregulation, and pharmacological inhibition of ALDH2 render LUAD cells more vulnerable to ferroptosis inducers and platinum-based chemotherapy. ALDH2 inhibits ferroptosis through the detoxification of 4-hydroxynonenal and malondialdehyde, the product of lipid peroxidation, as well as the production of NADH at the same time. Besides, ALDH2 deficiency leads to elevated intracellular pH (pHi), thus inhibiting the ERK/CREB1/GPX4 axis. Interestingly, ALDH2 is also regulated by CREB1, and the ALDH2 enzyme activity was decreased with elevated pHi. What's more, the elevated pHi caused by impaired ALDH2 activity promotes the biosynthesis of lipid droplets to counteract ferroptosis. At last, the effect of ALDH2 on ferroptosis and chemosensitivity is confirmed in patient-derived organoids and xenograft models. Collectively, this study demonstrates that ALDH2 deficiency confers sensitivity to platinum through ferroptosis in LUAD, and targeting ALDH2 is a promising new strategy to enhance the sensitivity of platinum-based chemotherapy for the treatment of LUAD patients.

A type of colorectal cancer (CRC)，Colitis-associated colorectal cancer (CAC)， is closely associated with chronic inflammation and gut microbiota dysbiosis. Berberine (BBR) has a long history in the treatment of intestinal diseases, which has been reported to inhibit colitis and CRC. However, the mechanism of its action is still unclear. Here, this study aimed to explore the potential protective effects of BBR on azoxymethane (AOM)/dextransulfate sodium (DSS)-induced colitis and tumor mice, and to elucidate its potential molecular mechanisms by microbiota, genes and metabolic alterations. The results showed that BBR inhibited the gut inflammation and improved the function of mucosal barrier to ameliorate AOM/DSS-induced colitis. And BBR treatment significantly reduced intestinal tumor development and ki-67 expression of intestinal tissue along with promoted apoptosis. Through microbiota analysis based on the 16 S rRNA gene, we found that BBR treatment improved intestinal microbiota imbalance in AOM/DSS-induced colitis and tumor mice, which were characterized by an increase of beneficial bacteria, for instance Akkermanisa, Lactobacillus, Bacteroides uniformis and Bacteroides acidifaciens. In addition, transcriptome analysis showed that BBR regulated colonic epithelial signaling pathway in CAC mice particularly by tryptophan metabolism and Wnt signaling pathway. Notably, BBR treatment resulted in the enrichment of amino acids metabolism and microbiota-derived SCFA metabolites. In summary, our research findings suggest that the gut microbiota-amino acid metabolism-Wnt signaling pathway axis plays critical role in maintaining intestinal homeostasis, which may provide new insights into the inhibitory effects of BBR on colitis and colon cancer.

Metastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN-the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses.

Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion.

To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion.

The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen.

During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs.

Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.

Human aldehyde dehydrogenases (ALDHs) are a group of 19 isoforms often overexpressed in cancer stem cells (CSCs). These enzymes play critical roles in CSC protection, maintenance, cancer progression, therapeutic resistance, and poor prognosis. Thus, targeting ALDH isoforms offers potential for innovative cancer treatments. Flavonoids, known for their ability to affect multiple cancer-related pathways, have shown anticancer activity by downregulating specific ALDH isoforms. This study aimed to evaluate 830 flavonoids from the PubChem database against five ALDH isoforms (ALDH1A1, ALDH1A2, ALDH1A3, ALDH2, ALDH3A1) using computational methods to identify potent inhibitors. Extra precision (XP) Glide docking and MM-GBSA free binding energy calculations identified several flavonoids with high binding affinities. MD simulation highlighted flavonoids 1, 2, 18, 27, and 42 as potential specific inhibitors for each isoform, respectively. Flavonoid 10 showed high binding affinities for ALDH1A2, ALDH1A3, and ALDH3A1, emerging as a potential multi-ALDH inhibitor. ADMET property evaluation indicated that the promising hits have acceptable drug-like profiles, but further optimization is needed to enhance their therapeutic efficacy and reduce toxicity, making them more effective ALDH inhibitors for future cancer treatment.

Cancer stem cells (CSCs) are a type of stem cell that possesses not only the intrinsic abilities of stem cells but also the properties of cancer cells. Therefore, CSCs are known to have self-renewal and outstanding proliferation capacity, along with the potential to differentiate into specific types of tumor cells. Cancers typically originate from CSCs, making them a significant target for tumor treatment. Among the related cascades of the CSCs, mammalian target of rapamycin (mTOR) pathway is regarded as one of the most important signaling pathways because of its association with significant upstream signaling: phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) pathway and mitogen‑activated protein kinase (MAPK) cascade, which influence various activities of stem cells, including CSCs. Recent studies have shown that the mTOR pathway not only affects generation of CSCs but also the maintenance of their pluripotency. Furthermore, the maintenance of pluripotency or differentiation into specific types of cancer cells depends on the regulation of the mTOR signal in CSCs. Consequently, the clinical potential and importance of mTOR in effective cancer therapy are increasing. In this review, we demonstrate the association between the mTOR pathway and cancer, including CSCs. Additionally, we discuss a new concept for anti-cancer drug development aimed at overcoming existing drawbacks, such as drug resistance, by targeting CSCs through mTOR inhibition.

Tumour microenvironment harbours diverse stress factors that affect the progression of multiple myeloma (MM), and the survival of MM cells heavily relies on crucial stress pathways. However, the impact of cellular stress on clinical prognosis of MM patients remains largely unknown. This study aimed to provide a cell stress-related model for survival and treatment prediction in MM. We incorporated five cell stress patterns including heat, oxidative, hypoxic, genotoxic, and endoplasmic reticulum stresses, to develop a comprehensive cellular stress index (CSI). Then we systematically analysed the effects of CSI on survival outcomes, clinical characteristics, immune microenvironment, and treatment sensitivity in MM. Molecular subtypes were identified using consensus clustering analysis based on CSI gene profiles. Moreover, a prognostic nomogram incorporating CSI was constructed and validated to aid in personalised risk stratification. After screening from five stress models, a CSI signature containing nine genes was established by Cox regression analyses and validated in three independent datasets. High CSI was significantly correlated with cell division pathways and poor clinical prognosis. Two distinct MM subtypes were identified through unsupervised clustering, showing significant differences in prognostic outcomes. The nomogram that combined CSI with clinical features exhibited good predictive performances in both training and validation cohorts. Meanwhile, CSI was closely associated with immune cell infiltration level and immune checkpoint gene expression. Therapeutically, patients with high CSI were more sensitive to bortezomib and antimitotic agents, while their response to immunotherapy was less favourable. Furthermore, in vitro experiments using cell lines and clinical samples verified the expression and function of key genes from CSI. The CSI signature could be a clinically applicable indicator of disease evaluation, demonstrating potential in predicting prognosis and guiding therapy for patients with MM.

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL.

The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear.

The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored.

A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes.

Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

Metastatic hepatocellular carcinoma (HC) is a serious health concern. The stemness of cancer stem cells (CSCs) is a key driver for HC tumorigenesis, apoptotic resistance, and metastasis, and functional mitochondria are critical for its maintenance. Cuproptosis is Cu-dependent non-apoptotic pathway (mitochondrial dysfunction) via inactivating mitochondrial enzymes (pyruvate dehydrogenase "PDH" and succinate dehydrogenase "SDH"). To effectively treat metastatic HC, it is necessary to induce selective cuproptosis (for halting cancer stemness genes) with selective oxidative imbalance (for increasing cell susceptibility to cuproptosis and inducing non-CSCs death). Herein, two types of Cu oxide nanoparticles (Cu4O3 "C(I + II)" NPs and Cu2O "C(I)" NPs) were used in combination with diethyldithiocarbamate (DD, an aldehyde dehydrogenase "ALDH" inhibitor) for comparative anti-HC investigation. DC(I + II) NPs exhibited higher cytotoxicity, mitochondrial membrane potential, and anti-migration impact than DC(I) NPs in the treated human HC cells (HepG2 and/or Huh7). Moreover, DC(I + II) NPs were more effective than DC(I) NPs in the treatment of HC mouse groups. This was mediated via higher selective accumulation of DC(I + II) NPs in only tumor tissues and oxidant activity, causing stronger selective inhibition of mitochondrial enzymes (PDH, SDH, and ALDH2) than DC(I)NPs. This effect resulted in more suppression of tumor and metastasis markers as well as stemness gene expressions in DC(I + II) NPs-treated HC mice. In addition, both nanocomplexes normalized liver function and hematological parameters. The computational analysis found that DC(I + II) showed higher binding affinity to most of the tested enzymes. Accordingly, DC(I + II) NPs represent a highly effective therapeutic formulation compared to DC(I) NPs for metastatic HC.

Aldehyde (ALDH2) dysfunction has been verified to contribute to human cancers.

To investigate the molecular mechanism and biological function of ALDH2 in colorectal cancer (CRC) progression.

Human CRC cells with high expression of ALDH2 were screened. After shRNA ALDH2 (sh-ALDH2) transfection, phenotypes [proliferation, apoptosis, acetaldehyde (ACE) accumulation, DNA damage] of CRC cells were verified using cell counting kit-8, flow cytometry, ACE assay, and comet assays. Western blotting was used for evaluation of the apoptosis proteins (Bax and Bcl-2) and JNK/p38 MAPK pathway-associated proteins. We subjected CVT-10216 (a selective ALDH2 inhibitor) to nude mice for establishment of SK-CO-1 mouse xenograft model and observed the occurrence of CRC.

The inhibition of ALDH2 could promote the malignant structures of CRC cells, including apoptosis, ACE level, and DNA damage, and cell proliferation was decreased in the sh-ALDH2 group, whereas ALDH2 agonist Alda-1 reversed features. ALDH2 repression can cause ACE accumulation, whereas ACE enhanced CRC cell features related to increased DNA damage. Additionally, ALDH2 repression led to JNK/P38 MAPK activation, and apoptosis, ACE accumulation, and DNA damage were inhibited after p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 addition. ACE accumulation and raised DNA damage were recognized in CVT-10216 treated-mouse tumor tissues in vivo.

The repression of ALDH2 led to ACE accumulation, inducing cell apoptosis and DNA damage by the JNK/p38 MAPK signaling pathway activation in CRC.

In the quest to manage hepatocellular carcinoma (HCC), the focus has shifted to a more holistic approach encompassing both data analytics and innovative treatments. Analyzing rich data resources, such as the cancer genome atlas (TCGA), and examining progressive therapies can potentially reshape the trajectory of HCC treatment.

To elucidate the immunological genes and the underlying mechanism of the combined Kombo knife and sorafenib regimen for HCC by analyzing data from TCGA and machine learning data.

Immune attributes were evaluated via TCGA's postablation HCC RNA sequencing data. Using weighted gene coexpression network analysis and machine learning, we identified genes with high prognostic value. The therapeutic landscape and safety metrics of the integrated treatment were critically evaluated across cellular and animal models.

Immune genes-specifically, peptidylprolyl isomerase A and solute carrier family 29 member 3-emerged as significant prognostic markers. Enhanced therapeutic outcomes, such as prolonged progression-free survival and an elevated overall response rate, characterize the combined approach, with peripheral blood mononuclear cells displaying potent effects on HCC dynamics.

The combination of Kombo knife with sorafenib is an innovative HCC treatment modality anchored in immune-centric strategies.

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.

Reactive aldehydes, for instance, formaldehyde and acetaldehyde, are important endogenous or environmental mutagens by virtue of their abilities to produce a DNA lesion called interstrand crosslink (ICL). Aldehyde-metabolizing enzymes such as aldehyde dehydrogenases (ALDHs) and the Fanconi anemia (FA) pathway constitute the main defense lines against aldehyde-induced genotoxicity. Biallelic mutations of genes in any one of the FA complementation groups can impair the ICL repair mechanism and cause FA, a heterogeneous disorder manifested by bone marrow failure (BMF), congenital abnormality and a strong predisposition to cancer. The defective ALDH2 polymorphism rs671 (ALDH2*2) is a known risk and prognostic factor for alcohol drinking-associated cancers. Recent studies suggest that it also promotes BMF and cancer development in FA, and its combination with alcohol dehydrogenase 5 (ADH5) mutations causes aldehyde degradation deficiency syndrome (ADDS), also known by its symptoms as aplastic anemia, mental retardation, and dwarfism syndrome. ALDH2*2 and another pathogenic variant in the alcohol-metabolizing pathway, ADH1B1*1, is prevalent among East Asians. Also, other ALDH2 genotypes with disease-modifying potentials have lately been identified in different populations. Therefore, it would be appropriate to summarize current knowledge of genotoxic aldehydes and defense mechanisms against them to shed new light on the pathogenic effects of ALDH2 variants together with other genetic and environmental modifiers on cancer and inherited BMF syndromes. Lastly, we also presented potential treatment strategies for FA, ADDS and cancer based on the manipulation of aldehyde-induced genotoxicity.

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk (odds ratio, 0.83; 95% confidence interval [CI], 0.75-0.92; P = 3.95 × 10 -4). C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates (hazards ratio, 1.33; 95% CI, 1.05-1.68; P log-rank = 1.90 × 10 -2). Furthermore, we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4 + T cells and macrophages. These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Hepatocellular carcinoma (HCC) is the most common digestive malignancyin the world, which is frequently diagnosed at late stage with a poor prognosis. For most patients with advanced HCC, the therapeutic options arelimiteddue to cancer occurrence of drug resistance. Hepatic cancer stem cells (CSCs) account for a small subset of tumor cells with the ability of self-renewal and differentiationin HCC. It is widely recognized that the presence of CSCs contributes to primary and acquired drug resistance. Therefore, hepatic CSCs-targeted therapy is considered as a promising strategy to overcome drug resistance and improve therapeutic outcome in HCC. In this article, we review drug resistance in HCC and provide a summary of potential targets for CSCs-based therapy. In addition, the development of CSCs-targeted therapeuticsagainst drug resistance in HCC is summarized in both preclinical and clinical trials. The in-depth understanding of CSCs-related drug resistance in HCC will favor optimization of the current therapeutic strategies and gain encouraging therapeutic outcomes.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale. Among the potential sorafenib targets, we identified aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a major role in alcohol metabolism. We validated the interaction of sorafenib with ALDH2 by orthogonal methods using pure recombinant protein, proving that this interaction is not mediated by other cellular components. Moreover, we showed that sorafenib inhibits ALDH2 activity, supporting a functional role for this interaction. Finally, we were able to demonstrate that both ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, our study allowed the identification of ALDH2 as a novel sorafenib target and sheds light on its potential role in both hepatocellular carcinoma and sorafenib resistance condition.

Fluctuations in the number of regulatory molecules and differences in timings of molecular events can generate variation in gene expression among genetically identical cells in the same environmental condition. This variation, termed as expression noise, can create differences in metabolic state and cellular functions, leading to phenotypic heterogeneity. Expression noise and phenotypic heterogeneity have been recognized as important contributors to intra-tumor heterogeneity, and have been associated with cancer growth, progression, and therapy resistance. However, how expression noise changes with cancer progression in actual cancer patients has remained poorly explored. Such an analysis, through identification of genes with increasing expression noise, can provide valuable insights into generation of intra-tumor heterogeneity, and could have important implications for understanding immune-suppression, drug tolerance and therapy resistance. In this work, we performed a genome-wide identification of changes in gene expression noise with cancer progression using single-cell RNA-seq data of lung adenocarcinoma patients at different stages of cancer. We identified 37 genes in epithelial cells that showed an increasing noise trend with cancer progression, many of which were also associated with cancer growth, EMT and therapy resistance. We found that expression of several of these genes was positively associated with expression of mitochondrial genes, suggesting an important role of mitochondria in generation of heterogeneity. In addition, we uncovered substantial differences in sample-specific noise profiles which could have implications for personalized prognosis and treatment.

Melanoma is a malignant skin tumor. This study aimed to explore and assess the effect of novel biomarkers on the progression of melanoma. Differently expressed genes (DEGs) were screened from GSE3189 and GSE46517 datasets of Gene Expression Omnibus database using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted based on the identified DEGs. Hub genes were identified and assessed using protein-protein interaction networks, principal component analysis, and receiver operating characteristic curves. Quantitative real-time polymerase chain reaction was employed to measure the mRNA expression levels. TIMER revealed the association between aldehyde dehydrogenase 2 (ALDH2) and tumor immune microenvironment. The viability, proliferation, migration, and invasion were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays. Total 241 common DEGs were screened out from GSE3189 and GSE46517 datasets. We determined 6 hub genes with high prediction values for melanoma, which could distinguish tumor samples from normal samples. ALDH2, ADH1B, ALDH3A2, DPT, EPHX2, and GATM were down-regulated in A375 and SK-MEL-2 cells, compared with the human normal melanin cell line (PIG1 cells). ALDH2 was selected as the candidate gene in this research, presenting a high diagnostic and predictive value for melanoma. ALDH2 had a positive correlation with the infiltrating levels of immune cells in melanoma microenvironment. Overexpression of ALDH2 inhibited cell viability, proliferation, migration, and invasion of A375/SK-MEL-2 cells. ALDH2 is a new gene biomarker of melanoma, which exerts an inhibitory effect on melanoma.