Colorectal cancer (CRC) is the third most common type of cancer worldwide and ranks among the leading causes of cancer-related deaths. During tumor progression, post-translational modifications, mainly the ubiquitin-proteasome system, are critical mediators of cellular metabolic reprogramming, including the metabolic changes of tumor development. Although TP53 mutations occur in approximately half of all CRC cases and could define their genetic makeup, precise therapeutic vulnerabilities remain largely unknown for the subgroup with wild-type p53. This study investigated the significant expression of Germ Cell-Specific Gene 2 (GSG2) in CRC. We demonstrated GSG2 is strongly increased in malignant colorectal tissues compared with adjacent benign tissues, and this high expression strongly predicts poor patient survival. Additionally, the results indicate that removing GSG2 effectively suppresses tumor growth in both in vitro systems and in vivo xenograft models. Mechanistically, GSG2 directly binds to the E3 ligase MDM2, and promoted MDM2-mediated ubiquitination and degradation of p53 in p53 wild-type CRC cells. Consequently, GSG2 enhances the cellular metabolic program, reprogramming glucose use toward aerobic glycolysis to meet the energy needs of uncontrolled growth. Thus, our findings reveal a novel way that p53 is silenced in cancers with wild-type TP53. GSG2 demonstrate control of the MDM2-p53 axis to promote the Warburg effect and drive CRC progression via p53 suppression.
PURPOSE:To compare perioperative hospital stay, chest tube retention time, and postoperative pain intensity between uniportal video-assisted thoracoscopic surgery (UVATS) and multiportal VATS (MVATS) for anatomical lung resection in patients with non-small cell lung cancer (NSCLC). METHODS:This retrospective cohort study enrolled 201 patients (83 in the UVATS group and 118 in the MVATS group) who underwent pulmonary lobectomy or segmentectomy. Daily postoperative chest drainage volume was recorded within the first three postoperative days. Postoperative pain intensity was assessed via the Visual Analog Scale (VAS) at 24 hours, 48 hours and 7 days after surgery. Opioid consumption, converted to morphine milligram equivalents (MME), was documented within the initial 48 postoperative hours. Chest tube retention time, postoperative length of stay and surgical complications were compared between groups. RESULTS:The UVATS group yielded significantly lower daily drainage volumes on postoperative day (POD) 1 (284.56 vs. 338.92 mL, P = 0.007), POD 2 (197.34 vs. 236.48 mL, P = 0.009) and POD 3 (130.58 vs. 159.12 mL, P = 0.004), as well as lower cumulative 72-hour drainage volume (612.48 vs. 743.52 mL, P = 0.001). Patients in the UVATS group reported remarkably lower VAS scores at 24 h (3.52 vs. 5.08, P<0.001), 48 h (2.98 vs. 4.22, P<0.001) and postoperative day 7 (2.21 vs. 2.75, P = 0.002), alongside reduced 48-hour opioid consumption (28.46 vs. 42.73 mg, P<0.001). Moreover, the UVATS group had shorter chest tube indwelling time (3.47 vs. 4.85 days, P<0.001) and shorter postoperative hospitalization (5.63 vs. 6.76 days, P = 0.001). The overall complication rate was also markedly lower in the UVATS group (14.46% vs. 27.12%, P = 0.033). CONCLUSION:Compared with MVATS, UVATS for NSCLC anatomical resection is associated with decreased postoperative pleural drainage, alleviated surgical pain, shortened chest tube indwelling and hospitalization duration, as well as reduced perioperative complications.
This study aimed to evaluate the prognostic significance of acute perioperative symptom burden as an independent predictor for long-term functional recovery and survival outcomes in patients with oral squamous cell carcinoma (OSCC) undergoing microvascular free flap reconstruction. A retrospective cohort of 355 OSCC patients treated between June 2022 and December 2024 at Henan Provincial People's Hospital was analyzed. All patients underwent primary tumor resection followed by immediate microvascular free flap reconstruction. Perioperative symptom burden was quantified using the validated MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Based on the median core severity score on postoperative day 3 (POD 3) of 5.79, patients were stratified into low symptom burden (n=178) and high symptom burden (n=177) groups. Over a 12-month follow-up period, comprehensive assessments encompassed long-term speech function measured by the Speech Handicap Index (SHI) and Percent Consonants Correct (PCI), swallowing function evaluated via the MD Anderson Dysphagia Inventory (MDADI), quality of life assessed by the University of Washington Quality of Life questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), as well as survival outcomes. Multivariate linear regression, Cox proportional hazards models, and subgroup analyses were employed to ascertain the independent prognostic value of symptom burden. Findings revealed that elevated perioperative symptom burden was significantly associated with delayed and incomplete functional recovery. At 12 months, the high symptom burden cohort demonstrated markedly worse SHI scores (29.2 vs. 19.2, t=12.45, P<0.001), reduced PCI (84.4% vs. 94.4%, t=-15.32, P<0.001), and lower MDADI scores (84.0 vs. 94.0, t=-14.88, P<0.001). Multivariate analysis identified the area under the curve (AUC) of the perioperative MDASI severity trajectory as an independent predictor for 12-month SHI (B=2.83, 95% CI 1.52-4.14, P=0.001) and UW-QOL scores (B=-3.82, 95% CI -5.14 to -2.50, P=0.001). Furthermore, a high symptom burden was independently correlated with poorer overall survival (Log-rank P=0.019) and recurrence-free survival (Log-rank P=0.025); Cox regression confirmed high symptom burden as an independent risk factor for overall survival (HR=1.78, 95% CI 1.06-2.99, P=0.029). Subgroup analyses upheld the robustness of these associations across diverse clinical and demographic strata. In conclusion, acute perioperative symptom burden transcends being a mere transient reflection of surgical trauma, serving instead as a pivotal independent prognosticator of long-term functional outcomes, quality of life, and survival in OSCC patients undergoing free flap reconstruction. Early identification and proactive management of perioperative symptoms may constitute a novel therapeutic avenue to enhance both oncologic and functional prognoses.
In this retrospective analysis, we used routinely collected clinical variables to develop a machine learning model for liver cancer diagnosis and examined the variables that contributed to model performance. We studied 3,629 people who were assessed because they were suspected to have liver cancer or other liver diseases. Patients who had pathologically confirmed liver cancer, and controls comprised of healthy subjects, patients with chronic hepatitis B, chronic hepatitis C, or cirrhosis. From 87 clinical parameters, least absolute shrinkage and selection operator regression was applied to identify candidate predictors. Nine machine learning algorithms were then trained and tested through 10-fold cross-validation and external validation in an independent cohort. Performance of the models was measured based on area under the receiver operating characteristic curve, sensitivity, specificity, calibration and decision curve analysis. The variables that contributed most to discrimination included carbohydrate antigen 19-9, alpha-fetoprotein-related indicators, liver function parameters, and inflammatory markers. Among the nine algorithms, Extreme Gradient Boosting achieved the highest discriminative performance, with an AUC of 1.000 in the training cohort and 0.937 in the validation cohort. In the SHapley Additive exPlanations analysis, carbohydrate antigen 19-9 made the largest contribution to the final model. These findings suggest that machine learning algorithms, particularly Extreme Gradient Boosting, may integrate heterogeneous clinical indicators and provide a useful auxiliary tool for distinguishing liver cancer from non-liver cancer conditions in individuals undergoing clinical assessment. Further prospective validation in high-risk surveillance cohorts is required before the model can be applied to early risk prediction or population-level screening.
Liver cancer, a primary malignancy of liver cells, exhibits high morbidity and mortality. Family with sequence similarity 64, member A (FAM64A) acts as an oncogene and modulates tumor progression in multiple cancers. However, the specific role of FAM64A in liver cancer development remains poorly elucidated. Thus, this work uncovered the action of FAM64A on liver cancer pathogenesis and cancer immunity and reveals the underlying mechanism. In this study, the FAM64A expression in liver cancer and its association with the overall survival were investigated using bioinformatics analysis. Tumor tissues and adjacent normal tissues were obtained from 64 liver cancer cases. Cell viability, invasion, and angiogenesis were assessed by CCK-8 method, Transwell invasion assay, and tube formation assay, respectively. The secretion levels of IFN-γ, IL-2, IL-10 and TGF-β were tested utilizing the ELISA assay. A xenograft tumor was created to monitor tumor growth in vivo. Results revealed that FAM64A expression was elevated in liver cancer. Clinically, high FAM64A levels correlated with shorter overall survival. Silencing of FAM64A restricted the malignant phenotypes of liver cancer cells, including proliferation, invasion, angiogenesis and immune escape. Furthermore, FAM64A knockdown restricted the activation of the VEGFA/AKT signaling. Conversely, VEGFA overexpression offset the above influences of FAM64A on liver cancer cells. Moreover, silenced FAM64A suppressed tumor growth, decreased CD31 and PD-L1 levels, increased CD8 and IFN-γ level, and reduced activation of the VEGFA/AKT signaling. Taken together, FAM64A is up-regulated in liver cancer and closely correlated with poor prognosis. Silenced FAM64A restrained proliferation ability, invasion capacity, angiogenesis and immune escape of liver cancer cells through inactivating the VEGFA/AKT signaling. FAM64A may be a valuable candidate target for liver cancer therapy.
This retrospective study aimed to investigate the predictive value of conventional ultrasonographic features combined with clinical factors for capsular invasion in patients with papillary thyroid carcinoma (PTC) with concurrent Hashimoto's thyroiditis (HT). A total of 262 patients with pathologically confirmed PTC and concurrent HT who underwent surgery at our institution from January 2018 to June 2024 were included as the training cohort. Patients were divided into capsular invasion and non-capsular invasion groups according to postoperative pathological findings. Clinical characteristics, conventional ultrasonographic features, and preoperative serum thyroid-stimulating hormone (TSH) levels were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of capsular invasion, and a nomogram model was constructed based on the selected variables. The predictive performance of the model was evaluated using receiver operating characteristic curves, calibration curves, decision curve analysis, and clinical impact curves. Univariate analysis showed that age, tumor diameter, postoperative lymph node metastasis, lesion margin, and blood flow signal were significantly associated with capsular invasion. Multivariate logistic regression analysis further identified age ≥55 years, larger tumor diameter, ill-defined lesion margin, and abundant blood flow signal as independent predictors of capsular invasion. The combined nomogram model achieved an area under the curve of 0.706 in the training cohort and 0.804 in the external validation cohort, showing better predictive performance than any single factor alone. Calibration curves, decision curve analysis, and clinical impact curves suggested acceptable model calibration and potential clinical utility. These findings indicate that a nomogram incorporating age, tumor diameter, lesion margin, and blood flow signal may provide a practical preoperative tool for estimating the risk of capsular invasion in patients with PTC and HT.
