Identification of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in alimentary tract malignancies.

BACKGROUND: Alimentary tract malignancies (ATM) caused nearly one-third of all tumor-related death. Cuproptosis is a newly identified cell death pattern. The role of cuproptosis-associated lncRNAs in ATM is unknown. METHOD: Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify prognostic lncRNAs by Cox regression and LASSO. Then a predictive nomogram was constructed based on seven prognostic lncRNAs. In addition, the prognostic potential of the seven-lncRNA signature was verified via survival analysis, the receiver operating characteristic (ROC) curve, calibration curve, and clinicopathologic characteristics correlation analysis. Furthermore, we explored the associations between the signature risk score and immune landscape, and somatic gene mutation. RESULTS: We identified 1211 cuproptosis-related lncRNAs and seven survival-related lncRNAs. Patients were categorized into high-risk and low-risk groups with significantly different prognoses. ROC and calibration curve confirmed the good prediction capability of the risk model and nomogram. Somatic mutations between the two groups were compared. We also found that patients in the two groups responded differently to immune checkpoint inhibitors and immunotherapy. CONCLUSION: The proposed novel seven lncRNAs nomogram could predict prognosis and guide treatment of ATM. Further research was required to validate the nomogram.

A novel nomogram for identifying candidates for adjuvant chemotherapy in patients with stage IB gastric adenocarcinoma.

BACKGROUND: The purpose of this research was to construct a novel predictive nomogram to identify specific stage IB gastric adenocarcinoma (GAC) populations who could benefit from postoperative adjuvant chemotherapy (ACT). METHOD: Between 2004 and 2015, 1889 stage IB GAC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) program database. Then Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were implemented. Finally, the predictive nomograms were constructed. The methods of area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to validate the clinical effectiveness of the models. RESULTS: Of these patients, 708 cases underwent ACT, while the other 1181 patients didn't receive ACT. After PSM, the patients in the ACT group presented a longer median overall survival (133 vs. 85 months, p = 0.0087). Among the ACT group, 194 (36.0%) patients achieving more prolonged overall survival than 85 months were regarded as the beneficiary population. Then the logistic regression analyses were performed, and age, gender, marital status, primary site, tumor size, and regional nodes examined were included as predicting factors to construct the nomogram. The AUC value was 0.725 in the training cohort and 0.739 in the validation cohort, which demonstrated good discrimination. And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. Furthermore, the prognostic nomogram predicting 1-, 3-, and 5-year cancer-specific survival presented good predictive ability. CONCLUSION: The benefit nomogram could guide clinicians in decision-making and selecting optimal candidates for ACT among stage IB GAC patients. And the prognostic nomogram presented great prediction ability for these patients.

De-escalating chemotherapy for stage I-II gastric neuroendocrine carcinoma? A real-world competing risk analysis.

BACKGROUND: The role of adjuvant chemotherapy in gastric neuroendocrine neoplasms (GNEC) has not been well clarified yet. The study was designed to investigate the potential effect of adjuvant chemotherapy in stage I-II GNEC patients and construct a predictive nomogram. METHOD: Stage I-II GNEC patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into chemotherapy and no-chemotherapy groups. We used Kaplan-Meier survival analyses, propensity score matching (PSM), and competing risk analyses. The predictive nomogram was then built and validated. RESULTS: Four hundred four patients with stage I-II GNEC were enrolled from the SEER database while 28 patients from Hangzhou TCM Hospital were identified as the external validation cohort. After PSM, similar 5-year cancer-specific survival was observed in two groups. The outcomes of competing risk analysis indicated a similar 5-year cumulative incidence of cancer-specific death (CSD) between the two cohorts (35.4% vs. 31.4%, p = 0.731). And there was no significant relation between chemotherapy and CSD in the multivariate competing risks regression analysis (HR, 0.79; 95% CI, 0.48-1.31; p = 0.36). Furthermore, based on the variables from the multivariate analysis, a competing event nomogram was created to assess the 1-, 3-, and 5-year risks of CSD. The 1-, 3-, and 5-year area under the receiver operating characteristic curve (AUC) values were 0.770, 0.759, and 0.671 in the training cohort, 0.809, 0.782, and 0.735 in the internal validation cohort, 0.786, 0.856, and 0.770 in the external validation cohort. Furthermore, calibration curves revealed that the expected and actual probabilities of CSD were relatively consistent. CONCLUSION: Stage I-II GNEC patients could not benefit from adjuvant chemotherapy after surgery. De-escalation of chemotherapy should be considered for stage I-II GNEC patients. The proposed nomogram exhibited excellent prediction ability.

The role of chemotherapy in patients with stage IB gastric adenocarcinoma: a real-world competing risk analysis.

BACKGROUND: This study aimed to investigate the potential effect of adjuvant chemotherapy in patients diagnosed with stage IB gastric adenocarcinoma (GAC). METHOD: A total of 1727 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and divided into the chemotherapy and no-chemotherapy groups. Then, the methods of Kaplan-Meier analysis, propensity score matching (PSM), and competing risk analysis were implemented. RESULTS: After PSM, no significant difference was found in the chemotherapy and no-chemotherapy groups in overall survival (OS) (p=0.4) and cancer-specific survival (CSS) (p=0.12) in survival curves. The competing risk analysis presented that the 5-year cumulative incidence of cancer-specific death (CSD) was significantly lower in patients receiving chemotherapy (11.5% vs. 20.8%, p=0.007), while no significant discrepancy was observed in other causes of death (OCD) in both groups (10.6% vs. 10.9%, p=0.474). Multivariable competing risks regression models presented a significant correlation between chemotherapy and CSD (HR, 0.51; 95%CI, 0.31-0.82; p=0.007). CONCLUSION: The stage IB GAC patients can benefit from adjuvant chemotherapy based on this competing risk analysis.

Application of Intraoperative Fluorescence Imaging with Indocyanine Green in the Difficult Gallbladder: A Comparative Study between Indocyanine Green-Guided Fluorescence Cholangiography and Conventional Surgery.

Background: In the difficult gallbladder, the rate of bile duct injury (BDI) remains high. To lessen iatrogenic biliary injury, we attempted to utilize indocyanine green (ICG)-guided fluorescence cholangiography during surgery to illuminate the extrahepatic biliary tract. Materials and Methods: According to admission criteria, 38 patients were diagnosed with difficult gallbladder and underwent percutaneous transhepatic gallbladder drainage (PTGBD). Consecutive patients who underwent ICG-assisted laparoscopic biliary surgery (n = 18, ICG group) or conventional laparoscopic biliary surgery (n = 20, white light [WL group) were enrolled in this study. ICG group received ICG fluorescent cholangiography via PTGBD tube during operation; 16 cases of laparoscopic cholecystectomy (LC) and 2 cases of LC plus laparoscopic common bile duct exploration (LC+LCBDE) were performed by fluorescent laparoscopy. In the WL group, 16 cases of LC, 1 case of laparoscopic subtotal cholecystectomy (LSC), and 3 cases of LC+LCBDE were performed under white light without ICG. Result: The biliary system was successfully established in the ICG group. Compared with the WL group, the anatomy of the Calot's triangle with severe abdominal adhesion or local inflammatory edema was more clearly displayed by fluorescence. Laparoscopic surgery was completed in both groups without conversion to laparotomy. There were no significant differences in surgery-related complications (P = .232) and postoperative hospital stay (P = .074) between the two groups. However, compared with the WL group, the ICG group had less intraoperative blood loss (P = .002) and shorter operation duration (P = .006). Conclusion: ICG fluorescence cholangiography has good clinical application value in the difficult gallbladder, which can avoid iatrogenic BDI, reduce surgery-related complications and intraoperative blood loss, and shorten the duration of surgery.

HSPA5 is a prognostic biomarker correlated with immune infiltrates in thyroid carcinoma.

INTRODUCTION: Thyroid carcinoma (THCA) is the most common endocrine malignancy. Recent research has shown heat shock protein family A (HSPA5) as a diagnostic and prognostic biomarker for various malignancies. Nevertheless, the role of HSPA5 in THCA is unclear. This study aims to explore HSPA5 expression in THCA and its potential diagnostic and therapeutic value for THCA. MATERIAL AND METHODS: We obtained the data of HSPA5 expression in THCA and normal thyroid tissues from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). We used the Shapiro-Wilk normality test, Levene's test, t-test, Dunn's test, Kruskal-Wallis test, Wilcoxon rank sum test, chi-square test, Fisher's exact test, and logistic regression to evaluate the relationship between the expression of HSPA5 and clinicopathological features. Kaplan-Meier method and Cox regression were applied to analyse the correlation between the expression level of HSPA5 and prognosis of THCA patients, and to construct a prognosis prediction model of THCA patients. Gene set enrichment analysis (GSEA) was applied to explore the potential pathway related to HSPA5 in THCA. RESULTS: HSPA5 expression was lower in THCA tissues than in normal thyroid tissues (p < 0.001). Low expression of HSPA5 in THCA patients was related to poorer T stage (p < 0.001), N stage (p < 0.001), pathologic stage (p < 0.001), tumour extrathyroidal extension (p < 0.001), residual tumour (p = 0.03), and progression-free interval (PFI) event (p = 0.002). Low HSPA5 expression was associated with poor PFI. According to the results of univariate analysis, THCA patients who had high HSPA5 levels had longer PFI (p = 0.042). Enrichment analysis via GO/KEGG showed that the top 10 genes related to HSPA5 were all enriched in the pathways related to endoplasmic reticulum function. Moreover, HSPA5 expression was related to immune infiltrating cells. CONCLUSIONS: Decreased expression of HSPA5 is associated with worse clinicopathological features, shorter PFI and higher immune infiltration level of multiple immune cells, which demonstrated that HSPA5 is a prognostic biomarker in THCA.