Journal of Cancer最新文献

Background: Few studies have analyzed the effect of matrix metalloproteinase (MMP) expression patterns on the tumor microenvironment (TME) during development of cervical cancer (CC). Methods: We elucidated the landscape and score of MMP expression in CC using single-cell RNA sequencing (scRNA-seq) and RNA sequencing datasets. Further, we aimed the MMPscore to probe the infiltration of immune cells. Further, MMP expression was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: We found MMPs were cell-type specific expressed in diverse types of CC cells, regulating the relative pathways of CC progression. Two distinct MMP expression patterns that associated infiltrated tumor microenvironment (TME) were identified. We discovered MMP expression patterns can predict the stage of tumor, subtype, stromal activity in the TME, genetic variation, and patient outcome. Patients with high MMPscore benefited from significantly better treatment and clinical outcomes. Conclusion: These results indicate high MMPscore in diverse cell types may regulate immune response and improve the survival of patients with CC, which assist in developing more effective immunization strategies.

Bladder cancer is the most prevalent type of cancer in Taiwan, and therefore, enhancing the diagnostic sensitivity of biomarkers for early-stage tumors and identifying therapeutic targets to improve patient survival rates are essential. Although Sushi Domain Containing 2 (SUSD2) dysfunction has been identified in several types of human cancer, its biological role in bladder cancer remains unclear. Analysis of The Cancer Genome Atlas revealed significantly higher expression of SUSD2 mRNA in bladder cancer tissues than in adjacent normal tissues. This elevated expression of SUSD2 significantly correlated with pathological stage (p = 0.029), pN stage (p < 0.001), and pM stage (p = 0.047). Univariate analysis revealed that high SUSD2 expression was associated with decreased overall survival (crude hazard ratio = 1.70, 95% confidence interval = 1.13-2.56, p = 0.01). Multivariate analysis revealed a significant correlation between high SUSD2 expression and poor survival outcomes (adjusted hazard ratio = 1.53, 95% confidence interval = 1.01-2.31, p = 0.043). IHC analysis revealed a significant correlation between elevated SUSD2 protein levels and unfavorable pathological stages (p < 0.001). SUSD2 suppression significantly reduced the proliferation, colony formation, and invasion of bladder cancer cells. In addition, cell cycle analysis revealed that SUSD2 knockdown induced G2/M phase arrestin bladder cancer cells. Tumor Immune Estimation Resource analysis indicated that expression of SUSD2 was significantly associated with macrophage infiltration and M2 macrophage polarization in bladder cancer. In addition, miR-383-5p directly targeted the 3'UTR of SUSD2, with its ectopic expression inhibiting the growth and motility of bladder cancer cells. Our study revealed that miR-383-5p/SUSD2 axis dysfunction may contribute to a poor prognosis for bladder cancer by affecting cell growth, metastasis, and the tumor microenvironment.

Minimally invasive radical hysterectomy (MIRH) is widely performed as a treatment for early-stage cervical cancer. However, in 2018, a randomized controlled trial (RCT) called the Laparoscopic Approach to Cervical Cancer (LACC) trial showed that MIRH had poorer oncologic outcomes compared to laparotomy. Since then, several clinical studies have supported this finding, and most surgeons now perform MIRH with limited surgical indications. However, most of the reported studies evaluated laparoscopic radical hysterectomy rather than robotic radical hysterectomy (RRH). Robotic surgery has advantages for complex surgical procedures in the deep and narrow pelvic cavity in cervical cancer, making it necessary to evaluate the benefits and potential harms of RRH individually. Based on this systematic review, RRH is a safe and effective alternative to abdominal approach for early-stage cervical cancer. RRH offers significant perioperative benefits, including reduced blood loss, shorter hospital stays, and fewer complications, without compromising oncologic outcomes such as overall survival and progression-free survival. Additionally, surgeons should aim to minimize tumor cell spillage into the peritoneal cavity by eliminating the use of uterine manipulators or vaginal colpotomy. Ongoing RCTs will reveal whether we can perform RRH without oncologic compromise in cervical cancer.

Background: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, particularly C677T and A1298C, have been implicated in various cancers, including non-Hodgkin lymphoma (NHL); however, their association with NHL risk remains inconclusive. Methods: We conducted an updated meta-analysis to assess the relationship between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. Relevant studies were identified through systematic literature searches in multiple databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Results: The meta-analysis included 32 studies (8222 cases vs. 12956 controls) for MTHFR C677T and 26 studies (6930 cases vs. 11611 controls) for the A1298C polymorphism. Our meta-analysis revealed no significant associations between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. However, subgroup analysis stratified by ethnicity and NHL subtype yielded interesting findings for the C677T polymorphism. Specifically, in the subgroup analysis of Caucasians, the C677T polymorphism was significantly associated with NHL risk (heterozygous: OR=1.16, 95% CI=1.02-1.32; allele comparison: OR=1.07, 95% CI=1.01-1.13). Furthermore, in the analysis stratified by NHL subtype, the C677T polymorphism was significantly associated with increased follicular lymphoma (FL) risk (homozygous: OR=1.25, 95% CI=1.02-1.53; recessive: OR=1.28, 95% CI=1.06-1.56). False-positive result possibility (FPRP) analysis verified that the association of the MTHFR C677T polymorphism with NHL risk for Caucasians and FL subtypes was a true positive and deserves attention. We also determined that the C677T polymorphism is an expression quantitative trait locus (eQTL) since it is associated with MTHFR gene expression. Conclusion: There was no overall association between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk, but stratified analyses revealed significant associations in specific subgroups. While meta-analyses inherently build upon existing studies, our work distinguishes itself by incorporating recent data, applying rigorous analytical techniques, and providing more evidence of the MTHFR C677T polymorphism as an eQTL.

Few robust biomarkers are available for distant metastatic colorectal cancer (CRC) patients. Aberrant high expression of CDH3 has been reported in advanced CRC patients, but the value of CDH3 as a biomarker for the diagnosis and prognosis of distant metastatic CRC patients remains to be evaluated. In this study, we explored the serum levels of CDH3 in different stages of CRC patients and sought to determine whether serum CDH3 serves as an independent biomarker for distant metastatic CRC patients. We analyzed the serum CDH3 levels by ELISA in a cohort of CRCs (n=96) and normal controls (n=28). We compared the serum CDH3 levels between normal controls and different stages of CRCs. As a potential diagnostic marker of distant metastatic CRC, the specificity and sensitivity of serum CDH3 were evaluated. Multivariate analysis was also performed to determine whether serum CDH3 was an independent risk factor. Moreover, the changes of serum CDH3 levels were monitored and analyzed before and after palliative chemotherapy. Serum levels of CDH3, CA24-2, CA19-9, CA72-4, and CEA were significantly elevated in distant metastatic CRCs. CA24-2 (r=0.24, P=0.01), CA19-9 (r=0.20, P=0.03), CA72-4 (r=0.64, P<0.0001), and CEA (r=0.31, P=0.0012) all had a certain correlation with CDH3. After three cycles of palliative chemotherapy, levels of CDH3, CA24-2, CA19-9, CA72-4, and CEA of partial response CRCs were reduced to 38.8% (95% confidence interval [CI]: 30.95%-53.77%), 57.73% (95% CI: 2.085%-73.83%), 50.33% (95% CI: 9.935%-79.42%), 74.74% (95% CI: 25.21%-88.00%), and 59.16% (95% CI: 12.65%-83.56%) of baseline, respectively. The areas under the receiver operating characteristic curves of CDH3, CA24-2, CA19-9, CA72-4, and CEA with chemotherapy response were 0.900, 0.597, 0.635, 0.608, and 0.507, respectively. Serum CDH3 is an effective serum biomarker for the diagnosis of distant metastatic CRCs and monitoring response to palliative chemotherapy in distant metastatic CRCs.

Background: There is an association between LUAD and TB, and TB increases the risk of lung adenocarcinogenesis. However, the role of TB in the development of lung adenocarcinoma has not been clarified. Methods: DEGs from TB and LUAD lung samples were obtained to identify TB-LUAD-shared DEGs. Consensus Clustering was performed on the TCGA cohort to characterize unique changes in TB transcriptome-derived lung adenocarcinoma subtypes. Prognostic models were constructed based on TB signatures to explore the characterization of subgroups. Finally, experimental validation and single-cell analysis of potential markers were performed. Results: We characterized three molecular subtypes with unique clinical features, cellular infiltration, and pathway change manifestations. We constructed and validated TB-related Signature in six cohorts. TB-related Signature has characteristic alterations, and can be used as an effective predictor of immunotherapy response. Prognostically relevant novel markers KRT80, C1QTNF6, and TRPA1 were validated by RT-qPCR. The association between KRT80 and lung adenocarcinoma disease progression was verified in Bulk transcriptome and single-cell transcriptome. Conclusion: For the first time, a comprehensive bioinformatics analysis of tuberculosis signatures was used to identify subtypes of lung adenocarcinoma. The TB-related Signature predicted prognosis and identified potential markers. This result reveals a potential pathogenic association of tuberculosis in the progression of lung adenocarcinoma.

Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.

Characterized by high invasiveness and expansive growth, melanoma progression is intricately regulated, with RNA m6A modifications playing a pivotal role. Among these regulators, METTL3 modulates the migratory capabilities of melanoma cells, specifically by modifying the RNA m6A of UCK2. The extract of Anoectochilusroxburghii, a plant known for its broad-spectrum antitumour properties, has been shown to effectively curb the invasion and migration of melanoma cells and impede tumour growth. The primary mechanism involves the downregulation of METTL3 expression. By doing so, the Anoectochilus roxburghii extract reduces the m6A level on the mRNA of UCK2, accelerating UCK2 mRNA degradation and, consequently, decreasing UCK2 expression. This process, in turn, suppresses gene expression within the Wnt/β-catenin pathway, contributing to its antimelanoma effects.

Purpose: Identify the hypoxia genes related to chemotherapy resistance of oral cancer, and construct a chemotherapy response model by machine learning algorithm. Methods: 72 oral cancer patients with complete chemotherapy records and chemotherapy reactions were screened from the Cancer Genome Atlas (TCGA) database. According to the chemotherapy reactions, they were divided into chemotherapy sensitive group and chemotherapy resistant group. The differential genes were screened by Limma package. Then the chemotherapy response gene were screened by univariate analysis. Based on the gene expression profile of chemotherapy response, four machine learning algorithms were used to construct the prediction model of chemotherapy response. The core genes were screened by lasso regression analysis. Finally, the prognosis and immune infiltration of the core genes were analyzed. The results were verified by immunohistochemistry (IHC). Results: We obtained 22 hypoxia related differential genes. Univariate analysis found 6 Chemotherapy response genes. Machine learning algorithms show that XGBoost have the best predictive performance for chemotherapy response. ALDOA is the core gene of chemotherapy resistance. Conclusions: Successfully constructed a chemotherapy prediction model for oral cancer by machine learning algorithm. Under hypoxia, the high expression of ALDOA is associated with chemotherapy resistance in oral cancer.

ENG/CD105 encodes a vascular endothelial glycoprotein and plays a crucial role in modulating angiogenesis. However, the significance of ENG expression, DNA methylation, immuno-response, and cordycepin (CD) regulation as diagnostic, prognostic, and therapeutic markers for breast invasive carcinoma (BRCA) remains unclear. As a result, ENG is decreased in BRCA tissues compared with corresponding healthy tissues. Five isoforms were found, and the utilization for ENG isoform (ENG-002) was the highest, suggesting its potential involvement in important roles in BRCA. ENG DNA was frequently altered in most types of cancer, and overall survival (OS) for mutant ENG was significantly longer than for wild-type cases. High expressions of ENG remarkably correlate with long relapse-free survival (RFS) for breast cancer (BC). Additionally, the ENG methylation level was higher in BRCA tissues compared with matched healthy tissues. The ENG expression and DNA methylation showed a significantly reverse correlation, demonstrating that ENG methylation may be a regulatory mechanism. By constructing diagnostic and prognostic models of ENG methylation for BRCA, we found four CpGs (CpG sites) that ranked with high importance. High methylation for cg14185922 of ENG in BRCA tissues showed shorter OS (high risk), indicating that ENG CpGs' methylation has potential as a diagnostic and prognostic biomarker for BRCA. Moreover, ENG might be a novel target for tumor immune response and immunotherapy in pancancer, including BC. CD, an adenosine analog and anti-cancer agent, increased ENG levels in a dose-dependent manner in animal models. This suggests that CD repressed BC growth and metastasis, at least partially through increasing the expression of the tumor suppressor gene ENG. Thus, our study successfully evaluated ENG/CD105 expression, DNA methylation, immune response, and CD regulation, which act as a novel diagnostic, prognostic, and therapeutic biomarker for BRCA. This research also fills critical knowledge gaps in this ENG/cancer field and highlights ENG's potential importance for the diagnosis, prognosis, and treatment of BRCA.