Wenzhen Yuan

Background: Prognostic assessment in gastric cancer (GC) remains challenging, as TNM staging has limited utility for individualized risk stratification. Systemic inflammation, metabolic status, immune function, and body composition are known to influence survival outcomes. This study aimed to evaluate the prognostic value of preoperative visceral adipose tissue index (VATI) and postoperative day 1 (POD1) glucose-to-lymphocyte ratio (GLR) in non-diabetic GC patients, and to develop an integrated prognostic model. Methods: This retrospective cohort study analyzed data from 339 GC patients, who were randomly assigned to a training cohort ( n = 272) and an internal validation cohort ( n = 67) in an 8:2 ratio using a computer-generated random sampling method. Cox regression was performed to identify independent predictors of overall survival (OS). Causal mediation analysis using a linear mediator model and a parametric accelerated failure-time survival model was performed to assess whether POD1 GLR mediated the association between preoperative VATI and OS. A TGV nomogram, integrating TNM stage, neoadjuvant chemotherapy (NAC), GLR, and VATI, was developed and validated using the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: Multivariable Cox regression analysis showed that NAC, advanced pTNM stage, high POD1 GLR, and low VATI were independently associated with poorer OS ( p < 0.05). Mediation analysis showed no significant indirect effect of POD1 GLR on the VATI–OS relationship (ACME, −3.82 days; 95% CI, −189.75 to 105.37; p = 0.899). Similar findings were obtained in the POD1 landmark and surgically adjusted sensitivity analyses. The TGV nomogram achieved 3- and 5-year AUCs of 0.850 and 0.798 in the training cohort and 0.785 and 0.729 in the internal validation cohort, respectively. The corresponding AUCs for TNM staging alone were 0.769 and 0.702 in the training cohort and 0.782 and 0.642 in the internal validation cohort. Training-cohort DCA suggested a higher net benefit for the TGV model than TNM staging across much of the evaluated threshold range at both 3 and 5 years. Conclusion: In this retrospective cohort of non-diabetic GC patients, low preoperative VATI and high POD1 GLR were independently associated with poorer OS. Mediation analysis provided no statistically significant evidence that POD1 GLR mediated the association between VATI and OS. The integrated model combining pTNM stage, NAC, GLR, and VATI showed potential for risk stratification, although its incremental prognostic value over established TNM-based models requires confirmation in independent external cohorts.

Background: Cancer cachexia is a multisystem syndrome characterized by progressive skeletal muscle atrophy, anorexia, and weight loss, imposing a substantial global health burden. Gastrointestinal cancer cachexia is highly prevalent, yet its pathogenesis remains poorly understood, and there is currently a lack of effective diagnostic methods and therapeutic strategies specifically targeting muscle atrophy. Identifying diagnostic and therapeutic targets for gastrointestinal cancer cachexia-related muscle atrophy represents a critical challenge. Methods: This study investigated the role of MG53 in gastrointestinal cancer cachexia. Serum MG53 levels were analyzed in patients, and experimental models examined tumor-derived MG53 effects on cancer cachexia-related muscle atrophy. Results: Elevated serum MG53 levels were found in gastrointestinal cancer cachexia patients. Tumor-derived MG53 aggravates cancer cachexia-related muscle atrophy by inhibiting the TLR4/PI3K/AKT/FOXO3a signaling pathway in muscle. Conclusions: MG53 is identified as a novel cancer cachexia factor driving gastrointestinal cancer cachexia-related muscle atrophy by inhibiting the TLR4/PI3K/AKT/FOXO3a signaling pathway in muscle. MG53 correlates with muscle atrophy, supporting its potential as a diagnostic biomarker and therapeutic target of gastrointestinal cancer cachexia.

Background Although laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) show comparable short- and long-term efficacy for treating locally advanced gastric cancer (LAGC), evidence on the cost-effectiveness of LDG versus ODG remains limited. This study aimed to evaluate the long-term cost-effectiveness of LDG versus ODG in patients with LAGC at different stages from a societal perspective in China. Methods A Markov model incorporating three health states (stable disease, disease progression, and death) was constructed based on data from the CLASS-01 trial. The outcome measures included incremental cost-effectiveness ratio (ICER) and quality-adjusted life years (QALYs). Cost-effectiveness was assessed by comparing the ICER to the willingness-to-pay (WTP) threshold. Sensitivity analyses were conducted to evaluate model uncertainty. Results In stage I patients, the model projected that LDG provided 0.29 incremental QALYs at an incremental cost of $819.33, yielding an ICER of $2829.98/QALY—below the WTP threshold, indicating potential cost-effectiveness conditional on the model parameters. Conversely, in stage II and III patients, ODG was associated with higher QALY gains than LDG (simulated incremental QALYs of − 0.14 and − 0.22, respectively), and the ICERs were negative (stage II: ICER − $7692.45 per QALY, incremental cost $1073.62; stage III: ICER − $4232 per QALY, incremental cost $913.41), suggesting that ODG was the cost-effective strategy within the simulation framework. Sensitivity analyses indicated that base-case findings were robust to parameter uncertainty. Conclusion Based on the model’s assumptions and parameterization, the simulated results indicate that LDG is likely cost-effective in stage I patients, while ODG appears more advantageous in stage II and III patients.

Objective: Patients with cancer often present with alterations in body composition and systemic inflammation. Guided by this observation, we sought to determine whether these factors are associated with postoperative complications in early-stage cervical cancer. Methods: In this retrospective cohort study, we analyzed data from 223 patients with early-stage cervical cancer treated at our center between July 2018 and December 2021.Postoperative complications were graded using the Clavien-Dindo classification. Systemic inflammatory markers were calculated from hematological parameters, while body composition indices were derived from computed tomography (CT) images at the third lumbar vertebra (L3) level and patient’s height. Group comparisons were performed using the χ² test, independent samples t-test, or Mann-Whitney U test, as appropriate. Binary logistic regression was applied to identify independent predictors of complications and conduct to sensitivity analysis to verify the robustness of the model. Results: Preoperative CT scans and hematological tests were performed a mean of 3.4 and 4.1 days before surgery, respectively. Postoperative complications were predominantly Grade 1 (n=124, 55.6%), followed by Grade 2 (n=69, 30.9%) and Grade 3 (n=30, 13.5%). No complications ≥ Grade 4 were observed. Patients with complications ≥ Grade 2 were more likely to undergo open surgery, present with larger tumors, exhibit lower skeletal muscle index (SMI) and prognostic nutritional index (PNI), higher visceral adipose tissue index (VATI), as well as greater intraoperative blood loss, lower preoperative and postoperative albumin levels, increased thrombotic risk, and longer hospital stays. Multivariate analysis identified that a higher complication grade (≥Grade 2) was significantly associated with low SMI (OR = 0.34, 95% CI = 0.18–0.64, P < 0.001), high VATI (OR = 1.04, 95% CI = 1.02–1.06, P < 0.001), and low PNI (OR = 0.91, 95% CI = 0.84–0.98, P = 0.008). No significant associations were found with IMATI, SATI, or systemic inflammatory markers (NLR, PLR, LMR, NPR, SII). After conducting sensitivity analyses on the key findings, the results remained robust. Conclusion: Sarcopenia, visceral adiposity, and low PNI are independently associated with a higher risk of clinically significant postoperative complications in patients with early-stage cervical cancer.

UBE2C (Ubiquitin-conjugating enzyme E2C) has been confirmed to be closely associated with the progression of various cancers, but its specific role and clinical diagnostic and prognostic value in prostate cancer (PRAD) remain unclear. This study systematically assessed the expression characteristics, prognostic significance, and genetic mutations of UBE2C in cancer patients by integrating data from databases such as TCGA, GEO, cBioPortal, and COSMIC. Experimentally, we explored the biological functions of UBE2C in the occurrence and development of PRAD using various methods, including functional enrichment analysis, CCK8 cell proliferation assay, colony formation assay, Transwell migration and invasion assay, Edu staining, 3D tumor spheroid culture, cell cycle analysis, apoptosis detection, and xenograft tumor models. After knocking down UBE2C expression, the proliferation ability, migration and invasion ability of PRAD cells, as well as the growth of xenograft tumors, were all inhibited, and the cell cycle process and apoptosis were changed accordingly. These findings provide favorable experimental evidence and theoretical support for UBE2C as a novel molecular marker for prognosis assessment in solid tumors.

Postoperative hyperglycemia is common in gastric cancer (GC) patients, especially during enteral and parenteral nutrition. While the importance of postoperative glycemic control in diabetic patients is well-recognized, the management of blood glucose (BG) in non-diabetic patients after surgery has received less attention. This study aimed to investigate the impact of postoperative BG levels on overall survival (OS) in non-diabetic GC patients. Additionally, we explored whether postoperative BG mediates the relationship between body composition parameters and postoperative survival, and to what extent this mediation occurs. A total of 349 patients who underwent curative surgery for GC in the Department of Oncology at The First Hospital of Lanzhou University from March 2017 to June 2021 were included in the study. Patients were stratified into groups based on postoperative BG levels, and differences in OS were analyzed. Univariate and multivariate Cox regression analyses were performed to identify independent factors influencing OS. Multivariate linear regression and correlation analyses were conducted to explore factors affecting postoperative blood glucose and its association with preoperative body composition parameters. A mediation analysis was conducted to assess the role of postoperative BG in mediating the effect of body composition on long-term survival, with the significance of the mediation effect tested using the bootstrap method. Age over 65, neoadjuvant chemotherapy, visceral adipose tissue index (VATI), surgical approach, pTNM stage, and postoperative hyperglycemia (HG) were identified as independent predictors of OS. Preoperative VATI, subcutaneous adipose tissue index, skeletal muscle density, random venous plasma glucose, hemoglobin, and total protein were significant factors influencing postoperative BG, and were significantly correlated with postoperative BG levels. Postoperative BG exhibited a significant negative mediating effect (-12.9%, 95%CI: -32.1% to -2.0%, p = 0.024) in the association between VATI and survival outcomes. Both preoperative body composition and postoperative BG are important factors influencing OS in non-diabetic GC patients. The positive impact of VATI on OS is partially offset by the negative mediating effect of postoperative BG. Therefore, postoperative glycemic control in non-diabetic patients should receive sufficient attention, with proactive prevention and management strategies to improve patient outcomes.

Radiotherapy is a vital treatment agent for lung adenocarcinoma (LUAD) patients, while radioresistance remains a major factor in treatment failure. Here, we aimed to elucidate how signal transducer and activator of transcription 1 (STAT1) affected sensitivity to carbon ion irradiation for LUAD cells in vivo and in vitro. The results of colony formation, CCK-8, EdU, and calcein-AM/PI double-staining assays demonstrated that the overexpression of STAT1 markedly enhanced the inhibitory effect of carbon ion irradiation on the viability of LUAD cells (A549 and PC9 cells). Lactate dehydrogenase (LDH) leakage assays identified ferroptosis as the predominant form of cell death induced by STAT1 overexpression in LUAD cells. Meanwhile, the ferroptosis-related PCR array confirmed heme oxygenase 1 (HO-1) as a potential effector molecule of STAT1-induced ferroptosis. Mechanistically, STAT1 overexpression resulted in phosphorylation at the serine 727 residue, triggering the upregulation of HO-1 expression and subsequent labile iron pool (LIP) accumulation. This process amplified the Fenton reaction, leading to increased reactive oxygen species (ROS), lipid peroxides (LPO), and glutathione (GSH) depletion. HO-1 knockdown eliminated the ferroptosis induced by the overexpression of STAT1. Furthermore, in vivo experiments showed that STAT1 overexpression enhanced the effect of carbon ion irradiation in inhibiting the growth of subcutaneous tumors in nude mice. These findings provide the foundation for the development of the STAT1-HO-1 axis as a radiosensitization target for LUAD patients.

Locally advanced gastric cancer (LAGC) poses a significant surgical challenge. While laparoscopic gastrectomy (LG) offers potential advantages, its cost-effectiveness relative to open gastrectomy (OG) in China remains uncertain. To compare the cost-effectiveness of LG and OG for LAGC in China. A Markov model compared the cost-effectiveness of LG and OG for LAGC. Probabilities and utilities were derived from published literature. Direct medical costs were obtained from the First Hospital of Lanzhou University. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life-year (QALY) gained, using a willingness-to-pay threshold of ¥268,074/QALY. Sensitivity analyses assessed model robustness. Across 1-, 3-, and 5-year time horizons, OG had lower total costs and greater effectiveness than LG for LAGC. At 5 years, OG had a total cost of ¥128,259 and 7.20 QALYs versus LG’s ¥136,668 and 7.18 QALYs; the ICER for OG was -¥474,758/QALY. OG dominated at the ¥268,074 willingness-to-pay threshold. Sensitivity analysis indicated that variations in LG and OG costs minimally influenced the cost-effectiveness. Probabilistic sensitivity analysis, performed across 10,000 iterations, consistently identified OG as the optimal strategy (100% of iterations). From a Chinese health economics perspective—a framework essential for informing national healthcare resource allocation—OG consistently demonstrated a superior cost-effectiveness compared with LG for LAGC across 1, 3, and 5 years. This longitudinal observation of sustained cost-effectiveness persisted despite the statistically insignificant differences in overall costs and effectiveness between the two procedures.