Journal of Cancer最新文献

Lactate metabolism plays a vital role in tumor progression. Currently, gastric cancer (GC) has a poor prognosis. Therefore, our research aimed to investigate novel biomarkers related to lactate metabolism in patients. Patient data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were divided into subtypes based on the expression of lactate metabolism-related genes (LMRGs). Based on the subtypes, we identified coiled-coil domain containing 80 (CCDC80) for further investigation. Univariate and multivariate Cox regression models were constructed to determine the prognostic value of CCDC80 in GC. We further explored the mechanism by which CCDC80 affects GC prognosis using gene set enrichment analysis (GSEA). Immune infiltration and drug sensitivity analyses were also performed. Finally, immunohistochemical staining was used to evaluate CCDC80 expression in normal and tumor tissues. We observed that CCDC80 was overexpressed in GC samples and was significantly associated with T and pathological stages. Multivariate Cox analysis identified high CCDC80 expression as an independent prognostic marker. GSEA indicated that the oxidative phosphorylation pathway was highly enriched in the low CCDC80 expression group. Moreover, CCDC80 was associated with immune cell infiltration, especially that of M2 macrophages. Patients with higher CCDC80 expression exhibited lower sensitivity to paclitaxel. In conclusion, our findings demonstrate that CCDC80 is a critical regulator in GC progression and immune response and is associated with lactate metabolism, and it could be used as a novel biomarker for prognostic and chemotherapy treatment purposes.

LY6H, a member of the lymphocyte antigen-6(LY6) gene family, is located on human chromosomes 6, 8, 11 and 19. This superfamily is characterized by the presence of LU domains. It has demonstrated its emerging significance in various cancers including adenocarcinoma, bladder cancer, ovarian cancer and skin cancer. However, comprehensive pan-cancer analyses have not been conducted to investigate its role in diagnosis, prognosis and immunological prediction. By conducting comprehensive analysis of patient data obtained from publicly available databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), University of Alabama at Birmingham (UALCAN), The Comparative Toxicological Genomics Database (CTD), cBioportal, cancerSEA, and UCSC, we systematically investigated the differential expression of LY6H in 33 different types of human tumors. Additionally, we thoroughly analyzed the diagnostic, prognostic, and immunoinfiltration value of LY6H. Simultaneously, we examined the correlation between LY6H and tumor stemness, methylation patterns, drug sensitivity, gene alterations as well as single cell functions. Furthermore, protein-protein interaction networks and gene-gene interaction networks for LY6H were constructed. Moreover, we also explored the network relationship between LY6H and chemical compounds or genes. The results revealed that LY6H exhibited high expression levels in most cancers which were further validated through Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Immunohistochemistry (IHC) analysis using Hepatocellular carcinoma (HCC) samples. Moreover, LY6H displayed early diagnostic potential in 12 tumors while also showing positive or negative correlations with prognosis across different tumor types. Additionally, it was found that LY6H played a pivotal role in regulating immune-infiltrating cells across multiple cancers whereas the correlation between LY6H expression and immune-related genes varied depending on their specific types. Furthermore, the expression of LY6H was significantly associated with DNA methylation patterns in 21 cancers. Therefore, LY6H could serve as an adjunctive biomarker for early tumor detection as well as a prognostic indicator for diverse malignancies.

Objective: To evaluate the efficacy, toxicity, and long-term outcomes of PD1 inhibitors plus chemotherapy versus re-irradiation/chemoradiotherapy in patients with unresectable locally recurrent T3-4 nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was conducted on 42 patients with recurrent nasopharyngeal cancer (NPC) after receiving immunochemotherapy or re-irradiation between February 2018 and May 2022 in Zhejiang Cancer Hospital. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression. Results: With a median follow-up duration of 28.7 months (ranging from 7.2 to 63.9 months), the 3-year OS rate was 23.3% in the re-irradiotherapy (RI) group (N = 24) and 59.6% in the immunochemotherapy (IC) group (N = 18) (p = 0.042). The 3-year PFS, LRFS, and DMFS rates were not significantly different between the two groups (PFS: 45.3% vs. 62.6%, P = 0.482; LRFS: 54.4% vs. 62.6%, P =0.891; DMFS: 89.8% vs. 100.0%, P = 0.489). The univariate analysis revealed that regimen (HR: 0.354, 95% CI: 0.130-0.962, P = 0.042) was significantly correlated with OS. Multivariate analysis also showed that treatment regimen (HR: 0.329, 95% CI: 0.12-0.970, P =0.044) was the only significant prognostic factor associated with OS. The most common late toxicities in the RI group were xerostomia, deafness, and nasopharyngeal necrosis. Of these, nasopharyngeal necrosis was present in 16 patients (66.7%) and in 10 patients (41.7%) at a grade 3 or above. Nasopharyngeal necrosis is the main cause of death in the RI group. In contrast, in the IC group, grade 3 or higher immune-related adverse events or late adverse events were not observed. Conclusions: For unresectable locally recurrent NPC, re-irradiation is an effective treatment; nevertheless, the survival obtains are usually surpassed by serious late complications. For these individuals, chemotherapy in addition to an anti-PD-1 checkpoint inhibitor may be a helpful course of treatment.

Disulfidptosis, a recently unveiled mechanism of demise, has been linked to an unfavorable prognosis in the context of hepatocellular carcinoma (HCC). However, few studies have focused on the causal link between disulfidptosis and HBV-related HCC (HBV-HCC). In this study, the Mendelian randomization (MR) analysis demonstrated that the risk of HCC increased with increasing genetic susceptibility to HBV, and the genetic changes of disulfidptosis were significantly associated with the increased risk of HBV-HCC. Within both the TCGA and GEO cohorts, it is possible to accurately forecast the prognosis of HBV-HCC by utilizing a risk score that is derived from a combination of GYS1, RPN1, SLC7A11, LRPPRC and CAPZB genes. GYS1, a potential therapeutic target for HBV-HCC, exhibits a remarkable positive correlation with immune infiltration and MSI when compared to other molecules. Furthermore, we demonstrated that silencing GYS1 effectively inhibits the tumor proliferation and metastasis of HBV-HCC in vitro and in vivo. Overall, this study expands the understanding of the potential roles of disulfidptosis in HBV-HCC and highlights GYS1 as a promising target for HBV-HCC.

Purpose: Colorectal cancer is the third most common cause of cancer death worldwide. We probed the correlations between E3 ubiquitin ligase (E3)-related genes (ERGs) and colon cancer prognosis and immune responses. Methods: Gene expression profiles and clinical data of patients with colon cancer were acquired from the TCGA, GTEx, GSE17537 and GSE29621 databases. ERGs were identified by coexpression analysis. WGCNA and differential expression analysis were subsequently conducted. Consensus clustering identified two molecular clusters. Differential analysis of the two clusters and Cox regression were then conducted. A prognostic model was constructed based on 10 machine learning algorithms and 92 algorithm combinations. The CIBERSORT, ssGSEA and TIMER algorithms were used to estimate immune infiltration. The OncoPredict algorithm and The Cancer Immunome Atlas (TCIA) predicted susceptibility to chemotherapeutic and targeted drugs and immunotherapy sensitivity. CCK-8, scratch-wound and RT‒PCR assays were subsequently conducted. Results: Two ERG-associated clusters were identified. The prognosis and immune function of patients in cluster A were superior to those of patients in cluster B. We constructed a prognostic model with perfect predictive capability and validated it in internal and external colon cancer datasets. We discovered significant discrepancies in immune infiltration and immune checkpoints between different risk groups. The group with high-risk had a reduced half-maximal inhibitory concentration (IC50) for some routine antitumor drugs and reduced susceptibility to immunotherapy. In vitro experiments demonstrated that the ectopic expression of PRELP inhibited the migration and proliferation of CRC cells. Conclusions: In summary, we identified novel molecular subtypes and developed a prognostic model, which will help a lot in the advancement of better forecasting and therapeutic approaches.

Metastasis is the leading cause of mortality in patients with malignant tumors, particularly characterized by peritoneal metastases originating from gastric, ovarian, and colorectal cancers. Regarded as the terminal phase of tumor progression, peritoneal metastasis presents limited therapeutic avenues and is associated with a dismal prognosis for patients. The epithelial-mesenchymal transition (EMT) is a crucial phenomenon in which epithelial cells undergo significant changes in both morphology and functionality, transitioning to a mesenchymal-like phenotype. This transition plays a pivotal role in facilitating tumor metastasis, with transcription factors being key mediators of EMT's effects. Consequently, we provide a retrospective summary of the efforts to identify specific targets among EMT-related transcription factors, aimed at modulating the onset and progression of peritoneal metastatic cancer. This summary offers vital theoretical underpinnings for developing treatment strategies against peritoneal metastasis.

N1-methyladenosine (m¹A) is a reversible epigenetic modification of RNAs. Aberrant m¹A modification levels due to dysregulation of m¹A regulators have been observed in multiple cancers. tRNA methyltransferase 10C (TRMT10C) can install m¹A in RNAs; however, its role in hepatoblastoma remains unknown. We conducted this study to identify causal polymorphisms in the TRMT10C gene for hepatoblastoma susceptibility in a cohort of Chinese children (313 cases vs. 1446 controls). The genotypes of four potential functional polymorphisms (rs7641261 C>T, rs2303476 T>C, rs4257518 A>G, and rs3762735 C>G) were determined in participants using TaqMan real-time PCR. The associations of these polymorphisms with hepatoblastoma susceptibility were estimated by logistic regression analysis adjusted for age and sex. All four polymorphisms were significantly associated with hepatoblastoma risk. In particular, under the recessive genetic model, these polymorphisms conferred an increased risk of hepatoblastoma: rs7641261 C>T [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI)=1.04-2.58, P=0.033], rs2303476 T>C (adjusted OR=1.87, 95% CI=1.16-3.02, P=0.010), rs4257518 A>G (adjusted OR=1.45, 95% CI=1.09-1.94, P=0.012), and rs3762735 C>G (adjusted OR=3.83, 95% CI=2.15-6.82, P<0.0001). Combined analysis revealed that kids had an increased risk of developing hepatoblastoma if they harbored at least one risk genotype (adjusted OR=1.94, 95% CI=1.48-2.54, P<0.0001). In addition, the combined risk effects of the four SNPs persisted across all the subgroups. We identified four hepatoblastoma susceptibility loci in the TRMT10C gene. Identifying more disease-causing loci may facilitate the development of genetic marker panels to predict individuals' hepatoblastoma predisposition.

Background: Esophageal squamous cell carcinoma (ESCC), one of the most aggressive gastrointestinal malignancies, remains an enormous challenge in terms of medical treatment and prognostic improvement. Based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases in R language, the myeloid-associated differentiation marker (MYADM) was confirmed using bioinformatics analysis and experimental verification. MYADM is upregulated in multiple cancer types; however, the oncogenic mechanism by which MYADM promotes ESCC remains largely unknown. Methods: In the present study, we used weighted gene coexpression network analysis to filter four hub genes (AKAP12, ITGA1, JAM2, and MYADM) in GSE45670 and GSE23400 that are related to the malignant progression of ESCC. Transcription factors and target miRNAs of the hub genes were predicted using the TarBase and JASPRAR databases, respectively, and a regulatory network was established. MYADM was selected based on the analysis of expression differences and prognostic value in ESCC. Next, we confirmed the level of MYADM in ESCC samples using immunohistochemistry of the tissue microarray. The molecular mechanisms of MYADM were further elucidated by experimental analyses, including Transwell assays, wound healing assays, and CCK8. Results: The correlation between MYADM levels and the clinical data of patients with ESCC was confirmed, including tumor differentiation, the node and metastasis stage, T stage, lymphatic metastasis, and postoperative distant metastasis. MYADM was significantly upregulated in ESCC and positively correlated with overall survival. MYADM induced cell proliferation, migration, invasion, and wound healing via the epithelial to mesenchymal transition (EMT) pathway in multiple experiments. Moreover, our results supported the hypothesis that MYADM promotes EMT during paclitaxel resistance. Conclusion: MYADM is closely correlated with ESCC progression, metastasis, and paclitaxel resistance and could be regarded as a novel biomarker and therapeutic target for ESCC patients.

Background: Dipeptidyl peptidase 7 (DPP7) is overexpressed in various tumors, but its role in colorectal cancer (CRC) remains unclear. Study the Impact of DPP7 on malignant progression and tumor immunity in CRC. Methods: We utilized Tumor Immune Estimation Resource 2.0 (TIMER2.0) and The Cancer Genome Atlas (TCGA) analyses to assess the expression of DPP7 in tumors and validated it through immunohistochemistry and immunoblotting. Additionally, we investigated the relationship between DPP7 and immune cell infiltration using single-sample Gene Set Enrichment Analysis (ssGSEA) analysis. Finally, the impact of DPP7 on cell proliferation, invasion, migration, and immune cell function in the tumor microenvironment was confirmed through cell experiments and animal studies. Results: DPP7 is highly expressed in CRC, and high expression of DPP7 is associated with poor prognosis. Cell experiments demonstrate that overexpression of DPP7 enhances the proliferation, migration, and invasion capabilities of colorectal cancer cells both in vitro and in vivo. Immune infiltration analysis and co-culture results indicate that overexpression of DPP7 suppresses the immune cell's cytotoxic function against tumors in the tumor microenvironment. Conclusions: DPP7 promotes the malignant potential of colorectal cancer cells and inhibits tumor immune function, thereby promoting the progression of colorectal cancer.

tsRNA (tRNA-derived small RNA) is derived from mature tRNA or precursor tRNA (pre-tRNAs). It is lately found that tsRNA's aberrant expression is associated with tumor occurrence and development, it may be used a molecule of diagnosis and therapy. Based on the cleavage position of pre-tRNAs or mature tRNAs, tsRNAs are classified into two categories: tRNA-derived fragments (tRFs) and tRNA halves (also named tiRNAs or tRHs). tsRNAs display more stability within cells, tissues, and peripheral blood than other small non-coding RNAs (sncRNAs), and play a role of stable entities that function in various biological contexts, thus, they may serve as functional molecules in human disease. Recently, tsRNAs have been found in a large number of tumors including such as lung cancer, breast cancer, gastric cancer, colorectal cancer, liver cancer, and prostate cancer. Although the biological function of tsRNAs is still poorly understood, increasing evidences have indicated that tsRNAs have a great significance and potential in early tumor screening and diagnosis, therapeutic targets and application, and prognosis. In the present review, we mainly describe tsRNAs in tumors and their potential clinical value in early screening and diagnosis, therapeutic targets and application, and prognosis, it provides theoretical support and guidance for further revealing the therapeutic potential of tsRNAs in tumor.