Comparison of bioelectrical impedance analysis and computed tomography for the assessment of muscle mass in patients with gastric cancer.

BACKGROUND: Low muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). METHOD: This cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. RESULTS: A total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07-1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772-0.908; female: AUC = 0.721, 95% CI: 0.598-0.843). CONCLUSIONS: Despite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.

Phase angle - A screening tool for malnutrition, sarcopenia, and complications in gastric cancer.

BACKGROUND: Patients with gastric cancer (GC) are more likely to experience malnutrition and muscle wasting. This study aims to investigate the potential of phase angle (PhA) as a screening tool for identifying malnutrition and sarcopenia in GC patients, as well as its association with short-term outcomes after radical gastrectomy. METHODS: This cross-sectional study enrolled patients diagnosed with GC at The Affiliated People's Hospital of Jiangsu University from October 2021 to September 2022. PhA was measured using bioelectrical impedance analysis. Computed tomography scan images were analyzed for body composition at the level of the third lumbar vertebra. Malnutrition was diagnosed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Sarcopenia diagnosis was based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. RESULTS: A total of 248 patients with GC were analyzed, including 188 patients who underwent radical gastrectomy. Of these, 71.4 % (n = 177) were male and 28.6 % (n = 71) were female and the median overall age was 68 years (IQR: 61-72 years). According to GLIM criteria, 49.2 % (n = 122) of patients were malnourished and 19.8 % (n = 49) had sarcopenia based on AWGS criteria. A one-degree decrease in PhA was significantly associated with GLIM malnutrition (Odds Ratio [OR] = 8.108, 95 % CI:3.181-20.665) and sarcopenia (OR = 2.903, 95 % CI:1.170-7.206). PhA exhibited fair to good diagnostic accuracy in identifying GLIM malnutrition (male: AUC = 0.797; female: AUC = 0.816) and sarcopenia (male: AUC = 0.814; female: AUC = 0.710). Low PhA (OR = 3.632, 95 % CI: 1.686-7.824) and operation time (OR = 2.434, 95 % CI:1.120-5.293) were independently associated with the risk of postoperative complications. CONCLUSIONS: PhA can serve as a reliable screening tool for identifying patients at risk of malnutrition, sarcopenia, and postoperative complications in GC.

CXCL2 acts as a prognostic biomarker and associated with immune infiltrates in stomach adenocarcinoma.

BACKGROUND: STAD ranked 5th most common in the incidence of malignant tumors and 3rd most common in the death rate of cancer worldwide. CXC chemokines affect the biological progress of various tumors, resulting in therapeutic failure. The role of CXCL2 in STAD was still a mystery. METHODS: The expression, prognostic value, and clinical function of CXCL2 were analyzed using several online bioinformatics tools and clinical tissues. RESULTS: CXCL2 level was significantly upregulated in STAD tissues. Strong correlation was obtained between CXCL2 level and immune cells as well as immune biomarkers. High CXCL2 expression in STAD was correlated with a favorable prognosis. Further analysis revealed that CXCL2, pTNM stage and age were independent factors affecting the prognosis of STAD patients. A predictive nomogram indicated that the calibration plots for the 1-year, 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the entire cohort. Validation analysis revealed that CXCL2 expression was upregulated in STAD and high CXCL2 level had a better overall survival. CXCL2 was associated with resistance to numerous drugs or small molecules in STAD. CONCLUSIONS: We identified CXCL2 as a novel therapeutic target and associated with immune infiltration in STAD.

Retraction notice to "PINK1 deficiency in gastric cancer compromises mitophagy, promotes the Warburg effect, and facilitates M2 polarization of macrophages" [Cancer Lett. 529 (2022) 19-36].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

PINK1 deficiency in gastric cancer compromises mitophagy, promotes the Warburg effect, and facilitates M2 polarization of macrophages.

Cancer cells are typically characterized by abnormal quality control of mitochondria, production of reactive oxygen species (ROS), dysregulation of the cell redox state, and the Warburg effect. Mutation or depletion of PTEN-induced kinase 1 (PINK1) or Parkin leads to mitophagy defects and accumulation of malfunctioning mitochondria, and is often detected in a variety of tumors. However, PINK1's role in the progression of gastric cancer (GC) remains unclear, with its main effect being on mitochondrial turnover, metabolic reprogramming, and tumor microenvironment (TME) alteration. To address these issues, we first assessed the expression levels of PINK1, mitophagy-associated molecules, ROS, HIF-1α, glycolysis-associated genes, and macrophage signatures in GC tissues and matched tumor-adjacent normal samples. In addition, GC cell lines (AGS and MKN-45) and xenograft mouse models were used to determine the mechanism by which PINK1 regulates mitophagy, metabolic reprogramming, tumor-associated macrophage (TAM) polarization, and GC progression. We found that PINK1 loss correlated with advanced stage GC and poorer overall survival. GC tissues with lower PINK1 levels showed compromised mitophagy signaling and enhanced glycolytic enzyme expression. In vitro experiments demonstrated that PINK1 deficiency promoted GC cell proliferation and migration through the inhibition of mitophagy, production of mitochondrial ROS, stabilization of HIF-1α, and facilitation of the Warburg effect under both normoxic and hypoxic conditions. Moreover, PINK1 deficiency in GC cells promoted TAM polarization toward the M2-like phenotype. Reintroduction of PINK1 or inhibition of HIF-1α effectively repressed PINK1 deficiency-mediated effects on GC cell growth, metabolic shift, and TAM polarization. Thus, mitophagy defects caused by PINK1 loss conferred a metabolic switch through accumulation of mtROS and stabilization of HIF-1α, thereby facilitating the M2 polarization of TAM to remodel an immunosuppressive microenvironment in GC. Our results clarify the mechanism between PINK1 and GC progression and may provide a novel strategy for the treatment of GC.