Role of autophagy-related genes in liver cancer prognosis.

Autophagy, a highly conserved process of protein and organelle degradation, has emerged as a critical regulator in various diseases, including cancer progression. In the context of liver cancer, the predictive value of autophagy-related genes remains ambiguous. Leveraging chip datasets from the TCGA and GTEx databases, we identified 23 differentially expressed autophagy-related genes in liver cancer. Notably, five key autophagy genes, PRKAA2, BIRC5, MAPT, IGF1, and SPNS1, were highlighted as potential prognostic markers, with MAPT showing significant overexpression in clinical samples. In vitro cellular assays further demonstrated that MAPT promotes liver cancer cell proliferation, migration, and invasion by inhibiting autophagy and suppressing apoptosis. Subsequent in vivo studies further corroborated the pro-tumorigenic role of MAPT by suppressing autophagy. Collectively, our model based on the five key genes provides a promising tool for predicting liver cancer prognosis, with MAPT emerging as a pivotal factor in tumor progression through autophagy modulation.

Variable Selection of Spatial Logistic Autoregressive Model with Linear Constraints.

In recent years, spatial data widely exist in various fields such as finance, geology, environment, and natural science. These data collected by many scholars often have geographical characteristics. The spatial autoregressive model is a general method to describe the spatial correlations among observation units in spatial econometrics. The spatial logistic autoregressive model augments the conventional logistic regression model with an extra network structure when the spatial response variables are discrete, which enhances classification precision. In many application fields, prior knowledge can be formulated as constraints on the parameters to improve the effectiveness of variable selection and estimation. This paper proposes a variable selection method with linear constraints for the high-dimensional spatial logistic autoregressive model in order to integrate the prior information into the model selection. Monte Carlo experiments are provided to analyze the performance of our proposed method under finite samples. The results show that the method can effectively screen out insignificant variables and give the corresponding coefficient estimates of significant variables simultaneously. As an empirical illustration, we apply our method to land area data.

A real-world study of anlotinib combined with GS regimen as first-line treatment for advanced pancreatic cancer.

Background: Anlotinib may boost the efficacy of pancreatic cancer (PC) treatment if timely added to the GS regimen (Gemcitabine, Tegafur-gimeracil-oteracil potassium); however, no data has been published. This study evaluated the safety and efficacy of anlotinib in combination with the GS regimen(hereafter referred to as the A+GS regimen) in the first-line treatment of patients with unresectable or metastatic PC. Methods: Patients with unresectable or metastatic PC treated at Yueyang Central Hospital and Yueyang People's Hospital between October 2018 and June 2022 were enrolled in this retrospective real-world investigation. Treatment efficacy was evaluated based on the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR), while the treatment safety was assessed by the frequency of major adverse events (AEs). Results: Seventy-one patients were included in this study, 41 in the GS group and 30 in the A+GS group. The A+GS group had a longer mPFS than the GS group (12.0 months (95% CI, 6.0-18.0) and 6.0 months (95% CI, 3.0-8.1)), respectively (P = 0.005). mOS was longer in the GS+A group) when compared with the GS group (17.0 months (95%CI, 14.0-20.0) and 10.0 months (95% CI, 7.5-12.5)), respectively (P = 0.018). The GS+A group had higher ORR (50.0% vs 26.8%, P = 0.045) and DCR (83.3% vs 58.5%, P = 0.026). Furthermore, there were no grade 4-5 AEs and no treatment-related deaths, and no discernible increase in AEs in the GS+A group when compared with the GS group. Conclusion: The A+GS regimen therapy holds great promise in managing treatment-naive advanced PC, except that future prospective studies with larger sample sizes and multiple centers are required to determine its efficacy and safety.

Immune-related keratitis is a rare complication associated with nivolumab treatment in a patient with advanced colorectal cancer: A case report.

Background: Immunotherapy has been widely used to treat Colorectal cancer but has also observe some immune-related adverse effects. With proper treatment, most irAE can be solved and the effect of immunotherapy will not be affected by temporary immunosuppression. However, there are few reports about corneal irAE, and the current understanding of irAE is incomplete. Here we report a metastatic colorectal cancer case of immune-related keratitis caused by nivolumab and to explore the occurrence of immune-related keratitis. Case description: Here we report the case of a 49-year-old man with mCRC who had no previous ocular disease but developed immune-related ulcerative keratitis after treatment with nivolumab. We summarize a large amount of literature to discuss the mechanism of immune-related keratitis. In addition, we conclude a method that may be used to detect the occurrence of immune keratitis, by monitoring MMPs and maspin in patients treated with nivolumab. We believe immune-related keratitis may be a rare complication of nivolumab in the treatment of mCRC. The effect of simple anti-infective therapy and repair-promoting drugs was not obvious, but the effect of glucocorticoid combined with autologous serum was significant. Conclusion: The mechanism of immune-related keratitis is that nivolumab destroys the immune microenvironment and ACAID, and affects corneal healing. Patients who use nivolumab can prevent immune keratitis by testing MMPs and maspin. The occurrence of immune keratitis may be a good indicator of the efficacy of ICI, and further study can be done in the follow-up.

Role of economic structural change in the peaking of China's CO2 emissions: An input-output optimization model.

To combat climate change, the Chinese government has announced that the country will reach its national carbon emission peak within 2030. Various scenario studies suggest that technological advances in energy, such as energy efficiency and renewables, would be the leading determining factors for the peak in China's carbon emissions. However, most of these studies have failed to reflect the fact that China is shifting its economy from energy-intensive industries to non-energy-intensive industries, which may play a vital role in mitigating carbon emissions. To assess how economic structural changes may contribute to carbon emissions, an input-output optimization model was constructed and scenario analyses were performed. This model introduced the input-output model integrated with an optimization model to ensure the balance of economic structure in an optimal result. The results show that in 2030, China could peak its carbon emissions at 12.41 Gt CO2eq (parts per giga ton; carbon dioxide equivalent) by adjusting its energy-intensive economic structure of which the key sectors are coke refined petroleum and nuclear fuel (C8), chemicals and chemical products (C9), other nonmetallic minerals (C11), basic and fabricated metals (C12), and electricity gas and water supply (C17). The continuous increase in the added value of the tertiary industry could maintain a high GDP growth rate of 5.6% when the secondary industry is restricted to reduce carbon emissions. Accelerating the pace of China's economic transformation will be very conducive to an earlier realization of peaking CO2 emissions because the inhibition effect of structural change on carbon emissions presents an increasing marginal trend. From a policy perspective, the analytical techniques in this study could provide valuable information for decision-makers to regulate sector capital investment and formulate practical industrial policies with implications for CO2 emissions.

Gastric cancer cells escape metabolic stress via the DLC3/MACC1 axis.

Metabolic stress usually occurs in rapidly growing gastric cancer (GC) when the energy demand exceeds the supply. Interestingly, cancer cells can somehow escape this stress. Some small Rho GTPases regulating cell migration can be activated by metabolic stress. DLC3 is a RhoA-specific GTPase-activating protein of unclear function in cancer. We hypothesized that it participated in metabolic stress escape. Methods: Metabolic stress in GC cells was induced by glucose deprivation, and DLC3 expression was detected. Based on the prognostic value, cell viability, motility and glycolysis were detected in DLC3 differently expressed GC cells in vitro and in vivo. DLC3 downstream targets were screened and verified. Chemotactic ability was evaluated to study DLC3 and its downstream signaling on metabolic stress escape. In addition, therapeutic strategies targeting DLC3 were explored. Results: DLC3 expression was lowered by metabolic stress in GC cells. DLC3 downregulation indicated poor cancer prognosis, and silencing DLC3 promoted GC cell proliferation and invasion. MACC1, an oncogene promoting GC growth and metastasis, was proved to be the downstream target of DLC3. Low DLC3 expression and high MACC1 expression indicated high recurrence rate after GC resection. DLC3 transcriptionally inhibited MACC1 expression via RhoA/JNK/AP-1 signaling, and subsequently suppressed GC cell glycolysis and survival under metabolic stress. The DLC3/MACC1 axis modulated the chemotaxis of GC cells from energy deficient area to glucose abundant area. Finally, lovastatin was found to be a promising therapeutic drug targeting the DLC3/MACC1 axis. Conclusions: The DLC3/MACC1 axis modulates GC glycolysis and chemotaxis to escape glucose deprivation. Lovastatin may inhibit GC by targeting the DLC3/MACC1 axis.

Life strategy and grazing intensity responses of Brachionus calyciflorus fed on different concentrations of microcystin-producing and microcystin-free Microcystis aeruginosa.

The occurrence of Microcystis blooms is a worldwide concern due to the numerous adverse effects on zooplankton. We therefore hypothesized that the cyanobacterium Microcystis aeruginosa is harmful to rotifer growth. Population and individual experiments were conducted with the same proportional volumes of Chlorella and Microcystis for given food densities. Life-table parameters, life-history traits, and the grazing intensity of Brachionus calyciflorus were evaluated after they had fed on microcystin-producing and microcystin-free Microcystis, both alone and combined with an edible alga (Chlorella pyrenoidosa), at concentrations of 1 × 105, 1 × 106, and 1 × 107 cells mL-1. The results showed that the interactive effects of food density and type appeared to be synergistic on generation time (T), net reproduction rate (R0), body length, swimming speed, and reproduction time. In contrast, these effects appeared to be antagonistic on intrinsic growth rate (r), finite rate of increase (λ), time to first brood, post-reproductive time and total offspring per female. The grazing rate of rotifers decreased with grazing time. Although the toxins released after grazing on M. aeruginosa had negative effects on rotifer growth and reproduction, B. calyciflorus changed its life strategy and grazing intensity in response to eutrophic conditions.

Effects of microcystin-producing and microcystin-freeMicrocystis aeruginosa on enzyme activity and nutrient content in the rotifer Brachionus calyciflorus.

Toxic cyanobacterial blooms disrupt freshwater recreation and adversely affect zooplankton. The freshwater cyanobacterium Microcystis aeruginosa produces microcystins, which are compounds toxic to rotifers. This study evaluated the effects of M. aeruginosa on enzyme activity and nutrient content in the rotifer Brachionus calyciflorus Pallas. The rotifers were fed on Chlorella pyrenoidosa, Scenedesmus obliquus, microcystin-producing and microcystin-free M. aeruginosa alone, and mixtures of green algae combined with toxic and nontoxic cyanobacteria, respectively. Activities of amylase, pepsase, trypsin, cellulase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were assessed after rotifer exposure to an environmental stressor. Nutrients analyzed were glycogen, protein, and triglyceride (TG). Single cyanobacteria and mixtures combined with toxic M. aeruginosa inhibited SOD activity. CAT and GPx activities significantly increased in rotifers fed with the mixture of Chlorella and toxic cyanobacteria. The activity of digestive enzymes increased compared with the Chlorella group in single and mixed diets. Glycogen and protein decreased in Microcystis mixtures, whereas TG content increased. The grazing rate (G) of the rotifers decreased with grazing time. High G value was observed with green algae in every treatment group. Although the toxins released after grazing on Microcystis affected rotifer enzyme activity and nutrient content, B. calyciflorus changed its physiological performance and grazing intensity with food type in response to eutrophic conditions.

Clinical significance of accurate identification of lymph node status in distant metastatic gastric cancer.

PURPOSE: The clinical consequences of accurately identifying lymph node (LN) status in distant metastatic gastric cancer (DMGC) are unclear. We aimed to determine the prognostic significance of N stage, positive LN (PLN) count, and the positive LN ratio (LNR). We also retrospectively compared survival outcomes of DMGC patients stratified by LN dissection (LND). RESULTS: LND was performed in 1593 patients. The CSS was significantly different between groups divided according to N stage, PLN, and LNR in DMGC patients who underwent LND. Lower LNR was an independent predictor of longer survival in all kinds of patients cohorts, whereas PLN was not such a predictor. PLN count correlated with LND number and LNR. No correlation existed between LNR and LND number. Undergoing LND and having a higher number of dissected LNs were associated with superior CSS. MATERIALS AND METHODS: Data from 1889 DMGC patients treated between 2004 and 2009, and documented in the Surveillance, Epidemiology, and End Results (SEER) registry, were reviewed. Pearson's correlation coefficient and the Chi-square test were used to study the relationships between LND number, PLN count, N stage, and the LNR. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis, with the log-rank test performed for univariate analysis (UVA) and the Cox proportional hazards model employed for multivariate analysis (MVA). CONCLUSION: LN metastatic variables play important roles in the prognostic evaluation and treatment decisions of DMGC patients. Accurate identification of LN status in DMGC patients is critical. LND performance is associated with increased survival and has clinical practicability.

Golgi phosphoprotein3 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis.

Golgi phosphoprotein3 (GOLPH3) is known as an oncoprotein and may be a prognostic biomarker in various tumors. Here we performed a meta-analysis on the association of GOLPH3 expression and survival in solid tumors. All eligible studies were identified in Embase, PubMed and Web of Science Databases up to November 2014. Data about overall survival (OS), and disease-free survival (DFS) were extracted and pooled hazard ratios (HRs) of GOLPH3 for survival were calculated by using a random-effect model. Heterogeneity and publication bias were also assessed. A total of 15 eligible studies which comprised of 2529 cases were included in this global analysis: 14 were dealing with overall survival (OS) and 6 were with disease-free survival (DFS). We found that GOLPH3 overexpression was associated with shorter OS (HR 2.487, 95% CI 1.897-3.258, P < 0.001) and DFS (HR 1.911, 95% CI 1.245-2.932, P = 0.003) in general carcinomas. Importantly, subgroup analysis suggested that overexpression of GOLPH3 correlated with shorter OS in urogenital system cancers (HR 4.258, 95% CI 1.81-4.91, P < 0.001). Moreover, publication bias was not significant (P > 0.05). In conclusion, the present meta-analysis showed that overexpression of GOLPH3 predicts poor prognosis in solid tumors.

Low expression of DLC1 is predictive of poor therapeutic efficiency of fluoropyrimidine and oxaliplatin as adjuvant chemotherapy in gastric cancer.

The Rho­GTPase­activating protein, deleted in liver cancer­1 (DLC1), has been reported to be a tumor suppressor. However, the prognostic value of DLC1 in gastric cancer (GC) remains to be fully elucidated. Fluoropyrimidine­oxaliplatin (FP­LOHP) combination therapy has been widely used for the adjuvant chemotherapy of GC, however, no reliable marker has been identified to determine its efficiency. Thus, the present study performed a retrospective investigation involving 251 patients with stage IB­III GC, who received adjuvant chemotherapy following radical resection and 37 patients with stage IV GC, who underwent palliative resection. The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses. Lower expression levels of DLC1 indicated a more advanced tumor­node­metastasis stage, increased lymph node metastasis, deeper tumor invasion, increased tumor size and a higher rate of distant metastasis. By contrast, relatively increased expression levels of DLC1 indicated a longer time to recurrence (TTR) [hazard ratio (HR), 2.232; P=0.004] and overall survival (OS) rate (HR, 2.910; P=0.001). Patients receiving FP­LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies. However, only the patients with DLC1­positive GC receiving FP­LOHP [DLC1 (+)/FP­LOHP (+)] exhibited a more favorable TTR and OS, compared with the patients with DLC1 (+)/FP­LOHP (­) (TTR, P=0.001; OS, P=0.020). No significant improvement in clinical outcome was observed in GC patients with low DLC1 receiving FP­LOHP treatment (TTR, P=0.270; OS, P=0.197). In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality. Only patients with DLC1­positive GC may have an improved treatment outcome from the use of FP­LOHP as adjuvant chemotherapy.

Prognostic Value of MACC1 in Digestive System Neoplasms: A Systematic Review and Meta-Analysis.

Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49-2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33-2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms.