Characterize molecular signatures and establish a prognostic signature of gastric cancer by integrating single-cell RNA sequencing and bulk RNA sequencing.

Gastric cancer is a significant global health concern with complex molecular underpinnings influencing disease progression and patient outcomes. Various molecular drivers were reported, and these studies offered potential avenues for targeted therapies, biomarker discovery, and the development of precision medicine strategies. However, it was posed that the heterogeneity of the disease and the complexity of the molecular interactions are still challenging. By seamlessly integrating data from single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq), we embarked on characterizing molecular signatures and establishing a prognostic signature for this complex malignancy. We offered a holistic view of gene expression landscapes in gastric cancer, identified 226 candidate marker genes from 3 different dimensions, and unraveled key players' risk stratification and treatment decision-making. The convergence of molecular insights in gastric cancer progression occurs at multiple biological scales simultaneously. The focal point of this study lies in developing a prognostic model, and we amalgamated four molecular signatures (COL4A1, FKBP10, RNASE1, SNCG) and three clinical parameters using advanced machine-learning techniques. The model showed high predictive accuracy, with the potential to revolutionize patient care by using clinical variables. This will strengthen the reliability of the model and enable personalized therapeutic strategies based on each patient's unique molecular profile. In summary, our research sheds light on the molecular underpinnings of gastric cancer, culminating in a powerful prognostic tool for gastric cancer. With a firm foundation in biological insights and clinical implications, our study paves the way for future validations and underscores the potential of integrated molecular analysis in advancing precision oncology.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

RAB10 Facilitates Colorectal Cancer Progression through Activation of the NF-κB Signaling Pathway.

Background: Colorectal cancer (CRC) is the third most prevalent malignancy globally, ranking as the second leading cause of cancer-related mortality. Emerging evidence highlights RAB10's involvement in the progression of various malignant tumors; however, its specific role in CRC remains unclear. Objective: To explore the oncogenic role of RAB10 in colorectal cancer progression by investigating its impact on NF-κB activation, aiming to identify a novel genetic biomarker for enhanced diagnosis and treatment of CRC. Methods: This study collected CRC tissue samples and utilized The Cancer Genome Atlas (TCGA) database for RAB10 expression verification through Western blot (WB). Cellular phenotype experiments were conducted on CRC cell lines, including quantitative real-time-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, and wound healing assay (HCT116 and SW480). Additionally, the impact of RAB10 on NF-κB signaling was assessed through qRT-PCR and WB. Results: RAB10 exhibited upregulation in CRC tissue samples compared to normal counterparts. Furthermore, RAB10 promoted the proliferation, migration, and invasion of HCT116 and SW480 cells. Notably, RAB10 induced NF-κB activation in CRC in vitro. Conclusion: This study revealed the oncogenic function of RAB10, explaining its role in activating NF-κB in CRC. The findings present RAB10 as a potential genetic biomarker for CRC diagnosis and treatment.

Establishment and validation of a prognostic nomogram for patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Colorectal neuroendocrine carcinoma is a relatively rare tumor, for which a prognosis prediction model is lacking. Based on the data from Surveillance, Epidemiology, and End Results (SEER) database and Fujian Cancer Hospital, the study constructed and validated a prognostic nomogram to assess overall survival of patients with colorectal neuroendocrine carcinoma(CRNEC). METHODS: We extracted data of patients diagnosed with CRNEC from the SEER database. These patients were randomly divided into a training cohort(N = 1425) and an internal validation cohort(N = 612). Data of patients diagnosed with CRNEC in Fujian Cancer Hospital was collected as an external validation cohort(N = 54). A prognostic nomogram was established. The performance of the nomogram was assessed with ROC curve, C-index and calibration curve. Decision curve analysis(DCA) and ROC curve were used to compare the prediction efficacy of nomogram with the seventh edition of the TNM classification of the American Joint Commission of Cancer. RESULTS: Nine variables were identified as independent predictors. Nomogram were established by the nine variables. AUC of the nomogram in predicting 1-, 3- and 5-year OS were 0.900, 0.912 and 0.915 in training cohort, 0.900, 0.925 and 0.919 in internal validation cohort, 0.900, 0.903 and 0.928 in external validation cohort. C-index were 0.845, 0.854 and 0.837. Calibration curves overlapped well with reference lines. Compared with the AJCC TNM staging system, the nomogram performed more effectively. Patients classified into low-risk and high-risk groups by the nomogram scores and performed well in stratification. CONCLUSION: The prognostic nomogram established and validated in our study can accurately and effectively predict the prognosis of patients with CRNEC.

Predictive value of computed tomography with coronal reconstruction in right hemicolectomy with complete mesocolic excision for right colon cancers: a retrospective study.

BACKGROUND: Understanding the vascular anatomy is critical for performing central vascular ligation (CVL) in right hemicolectomy with complete mesocolic excision (CME). This study aimed to investigate the predictive value of multi-slice spiral computed tomography (MSCT) with coronal reconstruction in right hemicolectomy with CME. METHODS: This is a retrospective descriptive study. Eighty patients with right colon cancer who underwent right hemicolectomy from December 2015 to January 2020 were included. The intraoperative reports (including imaging data) and MSCT images with coronal reconstruction were analysed and compared. The detection rates of the ileocolic vein (ICV) and ileocolic artery (ICA) roots and the accuracy in predicting their anatomical relationship were analysed. The detection rate and accuracy in predicting the location of the gastrocolic trunk of Henle (GTH), middle colic artery (MCA) and middle colic vein (MCV) were analysed. The distance from the ICV root to the GTH root (ICV-GTH distance) was measured and analysed. The maximum distance from the left side of the superior mesenteric artery (SMA) to the right side of the superior mesenteric vein (SMV), named the 'lsSMA-rsSMV distance', was also measured and analysed. RESULTS: In seventy-four (92.5%) patients, both the ICV and ICA roots were located; their anatomical relationship was determined by MSCT, and the accuracy of the prediction was 97.2% (72/74). The GTH was located by MSCT in 75 (93.7%) patients, and the accuracy of the prediction was 97.33% (73/75). The MCA was located by MSCT in 47 (58.75%) patients, and the accuracy was 78.72% (37/47). The MCV was located by MSCT in 51 (63.75%) patients, and the accuracy of the prediction was 84.31% (43/51). The ICV-GTH distance was measured in 73 (91.2%) patients, and the mean distance was 4.28 ± 2.5 cm. The lsSMA-rsSMV distance was measured in 76 (95%) patients, and the mean distance was 2.21 ± 0.6 cm. CONCLUSIONS: With its satisfactory accuracy in predicting and visualising the information of key anatomical sites, MSCT with coronary reconstruction has some predictive value in CME with CVL in right hemicolectomy.

Chemokine (C-X-C motif) ligand 1 is associated with tumor progression and poor prognosis in patients with colorectal cancer.

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients' samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.