Journal of Cancer最新文献

Background: Currently, there is few literature comprehensively analyzing landscape of cuproptosis-related genes (CRGs) in liver hepatocellular carcinoma (LIHC) with multiple omics approaches. Aims: Using comprehensive analysis, we aim to find out how CRGs works on LIHC. Method: With data from The Cancer Genome Atlas (TCGA) database, we constructed a prognostic prediction model for CGRs using LASSO regression analysis and performed immune infiltration analysis using the same dataset. To validate findings, we utilized RNA expression data from the International Cancer Genome Consortium (ICGC). Furthermore, we analyzed the enrichment and features of CRGs in epithelial cells using single-cell RNA sequencing (scRNA-seq) data. To validate the reliability of findings, we performed several experiments including RT-PCR, cloning formation assay, scratch assay, and Transwell assay. Result: We have constructed a high-precision risk scoring model composed of CRGs for predicting prognosis in TCGA-LIHC. Reliability of the risk prognosis model was confirmed through Kaplan-Meier curve analysis, time-dependent ROC analysis, and multivariate regression analysis. Furthermore, we found knocking down PDSS1 increased sensitivity of LIHC cells to copper ions, and both proliferation and migration abilities were significantly reduced. Finally, we comprehensively characterized the features of CRGs in LIHC through scRNA-seq. Conclusion: In this study, we introduce PDSS1 as a novel CRG in HCC. Utilizing scRNA-seq, we provide a comprehensive landscape of cuproptosis across various cell subtypes within the HCC tumor microenvironment. Furthermore, we detailed the characteristics of high PDSS1-expressing tumor cells, including their distinctive transcription factors, metabolic profiles, and interactions with different subtypes within the tumor microenvironment. This work not only elucidated the role of PDSS1 in HCC but also enhanced our understanding of cuproptosis dynamics during tumor progression.

Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.

Objective: We aimed to investigate the immunological significance of M2 macrophage-related genes in lung cancer (LC) patients, specifically focusing on constructing a risk score to predict patient prognosis and response to immunotherapy. Methods: We developed a novel risk score by identifying and incorporating 12 M2 macrophage-related genes. The risk score was calculated by multiplying the expression levels of risk genes by their respective coefficients. Through comprehensive enrichment analysis, we explored the potential functions distinguishing high- and low-risk groups. Moreover, we examined the relationship between patients in different risk groups and immune infiltration as well as their response to immunotherapy. The single-cell RNA sequencing data were acquired to ascertain the spatial pattern of RNF130 expression. The expression of RNF130 was examined using TCGA datasets and verified by HPA. The qRT-PCR was employed to examine RNF130 expression in LC cells. Finally, in vitro experiments were carried out to validate the expression and function of RNF130. Results: Our results indicated that the risk score constructed from 12 M2 macrophage-related genes was an independent prognostic factor. Patients in the high-risk group had a significantly worse prognosis compared to those in the low-risk group. Functional enrichment analysis showed a significant relationship between the risk score and immunity. Furthermore, we explored immune infiltration in different risk groups using seven immune algorithms. The results demonstrated a negative correlation between high-risk group patients and immune infiltration of B cells, CD4+ cells, and CD8+ cells. We further validated these findings using an immunotherapy response database, which revealed that high-risk patients were more likely to exhibit immune evasion and might have poorer immunotherapy outcomes. Additionally, drug sensitivity analysis indicated that patients in the high-risk group were more sensitive to certain chemotherapeutic and targeted drugs than those in the low-risk group. Single-cell analysis indicated that macrophages were the primary site of RNF130 distribution. The results from the TCGA and HPA database demonstrated a trend toward a low expression of RNF130 in LC. Finally, in vitro experiments further validated the expression and function of RNF130 in LC cells. Conclusions: The high-risk group constructed with M2 macrophage-related genes in LC was closely associated with poor prognosis, low immune cell infiltration, and poorer response to immunotherapy. This risk score can help differentiate and predict the prognosis and immune status of LC patients, thereby aiding in the development of precise and personalized immunotherapy strategies.

Prior research has proposed a potential association between lung cancer and inflammatory cytokines, yet the specific causal relationship remains unclear, especially across various lung cancer pathologies. This study utilized bidirectional Mendelian randomization (MR) to explore these causal connections, unveiling novel insights. Our research revealed distinctive inflammatory cytokine profiles for each subtype of lung cancer and identified potential biomarkers that could refine diagnostic and therapeutic approaches. We applied two-sample Mendelian randomization, leveraging genetic variance data from three extensive genome-wide association studies (GWAS) focusing on different lung cancer types (lung adenocarcinoma: 1590 cases and 314,193 controls of healthy individuals of European descent; lung squamous cell carcinoma: 1510 cases and 314,193 controls of European ancestry; small cell lung cancer: 717 cases and 314,193 controls of European ancestry). A separate GWAS summary on inflammatory cytokines from 8,293 healthy participants was also included. The inverse variance weighting method was utilized to examine causal relationships, with robustness confirmed through multiple sensitivity analyses, including MR-Egger, weighted median, and MR-PRESSO. Our analysis revealed that elevated levels of IL_1RA were associated with an increased risk of lung adenocarcinoma (OR: 1.29, 95% CI: 1.02-1.64, p = 0.031), while higher MCP_1_MCAF levels correlated with a decreased risk of lung squamous cell carcinoma (OR: 0.77, 95% CI: 0.61-0.98, p = 0.031). Furthermore, IL_10, IL_13, and TRAIL levels were positively associated with lung squamous cell carcinoma risk (IL_10: OR: 1.27, 95% CI: 1.06-1.53, p = 0.012; IL_13: OR: 1.15, 95% CI: 1.06-1.53, p = 0.036; TRAIL: OR: 1.15, 95% CI: 1.06-1.53, p = 0.043). No association was found between inflammatory cytokine levels and small cell lung cancer development, whereas SDF_1A and B-NGF were linked to an increased risk of this cancer type (SDF_1A: OR: 1.13, 95% CI: 1.05-1.21, p = 0.001; B-NGF: OR: 1.13, 95% CI: 1.01-1.27, p = 0.029). No significant relationship was observed between the 41 circulating inflammatory cytokines and lung adenocarcinoma or squamous cell carcinoma development. Our findings indicate distinct associations between specific inflammatory cytokines and different types of lung cancer. Elevated IL_1RA levels are a risk marker for lung adenocarcinoma, whereas higher MCP_1_MCAF levels appear protective against lung squamous cell carcinoma. Conversely, elevated levels of IL_10, IL_13, and TRAIL are linked with an increased risk of lung squamous cell carcinoma. The relationships of SDF_1A and B-NGF with small-cell lung cancer highlight the complexity of inflammatory markers in cancer development. This study provides a nuanced understanding of the role of inflammatory cytokines in lung cancer, underscoring their potential in refining diagnosis and treatment stra

Background: The short-term and long-term outcomes of laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) have been subject to controversy with various reconstruction techniques of Billroth-I, Billroth-II, Roux-en-Y, and Uncut. This study aims to compare the short-term and long-term outcomes of LADG and TLDG as well as the outcomes of different anastomoses. Methods: This study enrolled patients with gastric cancer at the First Affiliated Hospital of Nanjing Medical University (NMUH) between 2017 and 2021. Postoperative complications were classified according to the Clavien-Dindo grade. Exclusion criteria included metachronous and synchronous malignancy and palliative surgery. The Kaplan-Meier analysis was applied to assess 5-year prognosis between two groups. Results: This study included 1221 cases with an overall complication rate of 17.37% for LADG, which was significantly higher than TLDG's 10.72%. The incidence of anastomosis-related complications was 4.79% for LADG and 1.13% lower for TLDG. LADG and TLDG did not show significant difference for Grade III-V complications and resected lymph nodes. The postoperative stay was shorter for TLDG than LADG, and R-Y had a longer postoperative stay than B-II and Uncut after combining LADG and TLDG. The operation time was shorter in TLDG cases than that in LADG cases. The 5-year OS of the TLDG group was not significantly better than that of the LADG group. Conclusion: TLDG is superior in overall complication rate, anastomosis-related complication rate, postoperative stay and operation time to LADG. No difference of OS was observed between LADG and TLDG. Four anastomoses had no convincing evidence of being superior in complications rates, post-op stay, and harvested lymph nodes to each other.

Nasopharyngeal carcinoma (NPC) presents a significant therapeutic challenge due to its aggressive nature and limited treatment options. Although morusin, a compound found in traditional Chinese medicines, exhibits significant tumor-inhibiting properties, its specific effects on NPC proliferation remain unclear. This study aims to elucidate the inhibitory effects of morusin on NPC survival and proliferation while exploring the underlying mechanisms through the utilization of network pharmacology, molecular docking, and experimental validation in vitro and in vivo. Network pharmacology analysis identified 117 potential targets of morusin against NPC, with 8 hub targets including AKT1, BCL2, CASP3, CTNNB1, ESR1, HSP90AA1, MMP9, STAT3, and the IL-17 signaling pathway. Further investigation of public data indicated that the expression levels of BLC2, CASP3, CTNNB1, HSP90AA1, and STAT3 in NPC tissue were significantly elevated compared to normal nasopharyngeal tissue. Docking studies exposed robust binding activity between morusin and key gene molecules. Additionally, biological assays demonstrated that morusin effectively inhibits NPC growth both in vivo and in vitro. Through a comprehensive investigation, this study identified the pharmacological mechanisms essential for morusin-induced inhibition of NPC growth by targeting multiple molecular targets and signaling pathways. These findings show the potential to contribute to the development of novel clinical agents for treating NPC.

Circular RNAs (circRNAs) are involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the mechanisms of aberrant expression and functions of circ_0006168 in ESCC. In this study, real-time qPCR and fluorescence in situ hybridization (FISH) are adopted to estimate the expression and localization of circ_0006168 in cancer tissues and cells. Methylated RNA immunoprecipitation (MeRIP) was performed to detect the N⁶-methyladenosine (m⁶A) modification of circ_0006168. Gain- and loss-of-functions of circ_0006168 were performed to identify its role in ESCC progression. RNA-binding protein immunoprecipitation (RIP) was used to detect the interaction of circ_0006168 with IGF2BP2. Luciferase reporter assay and RIP are used to confirm the circ_0006168/miR-384/STAT3 ceRNA network. Our results showed that the expression of circ_0006168 was upregulated in ESCC tissues and cells. METTL3-mediated m⁶A modification increased the expression of circ_0006168 via IGF2BP2-dependent way in TE-1 cells. Circ_0006168 promoted cell proliferation, migration, invasion, cell cycle progression and inhibited cell apoptosis, while knockdown of circ_0006168 had the reverse effects. Mechanistically, circ_0006168 acted its functions via miR-384/STAT3/Snail axis in TE-1 cells. In conclusion, circ_0006168 is upregulated in ESCC and m⁶A methylation increased its expression via IGF2BP2. CircRNA_0006168 promotes cell migration, invasion by regulating EMT via miR-384/STAT3/Snail axis in ESCC.

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

Objectives: miR-125a-5p's role in various cancers has been recognized, yet its specific function in pancreatic cancer (PCa) demands further exploration. This study aimed to reveal the potential function of miR-125a-5p in PCa. Methods: With publicly available databases, we explored the expression pattern and prognostic relevance of miR-125a-5p and STAT3 in PCa. We measured miR-125a-5p levels in PCa tissues, plasma and cell lines using RT-qPCR. To assess functional effects, PANC-1 cells were transfected with miR-125a-5p mimics and inhibitors, as well as siRNA-STAT3 and STAT3 vectors. Cell proliferation was estimated using Cell Counting Kit-8, while autophagy and apoptosis were examined by transmission electron microscopy and TUNEL assay, respectively. Western blot analysis was also performed to detect proteins associated with autophagy and apoptosis. The regulatory relationship of miR-125a-5p on STAT3 was verified using a dual luciferase reporter assay. The influence of miR-125a-5p on tumor development was evaluated in xenograft models. Results: Decreased expression of miR-125a-5p was found in PCa samples, and low expression of miR-125a-5p was associated with a poorer prognosis in PCa patients. Functional assays indicated miR-125a-5p suppressed cell growth while enhancing apoptosis and autophagy in PCa cells. STAT3 represents a specific target of miR-125a-5p, inhibiting STAT3 reversed the inhibitory effect of overexposed miR-125a-5p. Additionally, miR-125a-5p significantly restrained tumor development in mice. Conclusions: miR-125a-5p functions as a tumor suppressor in PCa by targeting STAT3, thereby inducing autophagy and apoptosis. Its regulatory role underscores its potential as a valuable biomarker for PCa diagnosis and therapy, warranting further clinical investigation.

Background: Otopetrin 2 (OTOP2) is a conserved ion channel protein that regulates cell signaling, growth, and development. Although the role of OTOP2 in tumor suppression has been reported in several studies of colon adenocarcinoma (COAD), characterized its immunomodulatory effects on tumors. Methods: We conducted a thorough analysis of OTOP2 expression and its association with clinicopathological characteristics, immune-related pathways, and immune-related molecules in individuals with COAD using data from The Cancer Genome Atlas (TCGA) and confirmed the findings with tissue microarrays (TMAs). We conducted in vitro assays to demonstrate the tumor suppressive effect of OTOP2 in COAD cells. Results: OTOP2 expression was abnormal in multiple types of tumors and was significantly downregulated in patients with COAD (P<0.001). Moreover, the presence of OTOP2 was linked to enhanced survival in individuals diagnosed with COAD. In vitro experiments showed that OTOP2 suppressed cell proliferation, migration, invasion, and adhesion. Gene set enrichment analysis of the TCGA database indicated that OTOP2 was positively correlated with antigen presentation pathways and T cell responses. The immunophenoscore (IPS) indicated a positive correlation between OTOP2 expression and MHC molecule expression (P<0.001) as well as between OTOP2 expression and the number of effector cells (P<0.01). Immunohistochemical analysis of the TMAs revealed strong associations between OTOP2 expression and MHC-I, TAP1, and TAP2 expression, and between OTOP2 expression and CD8⁺ T cell infiltration in COAD patients. Conclusion: In summary, our research emphasizes the role of OTOP2 as a tumor suppressor, suggesting its use as a prognostic indicator and predictor of response to immunotherapy in COAD patients.