Kiss-1 and Kiss-1R have been suggested as a novel pair of metastasis suppressors for several human solid tumours, however, their role in colorectal cancer remains largely unknown. Therefore, the aim of this study was to investigate the role and signal transduction of Kiss-1 and Kiss-1R in colorectal cancer. Ribozyme transgenes were used to knockdown high expression of Kiss-1 and Kiss-1R in HT115 and HRT18 cells. The stabilized transfected cells were then used to deduce the influence of Kiss-1 and Kiss-1R on the function of colorectal cancer cells by in vitro assays and ECIS assay. The effect of Kiss-1 on MMPs related to tumour metastasis was also deleted by zymography. The mRNA and protein expression of Kiss-1 and Kiss-1R, and their correlation to the clinical outcome in human colorectal cancer were investigated using real-time PCR and IHC respectively. Knocking down Kiss-1 resulted in increased invasion and migration of colorectal cancer cells. Kisspeptin-10 decreased cellular migration of colorectal cancer cells and required ERK signaling as shown during the ECIS based analyses. Reduction of MMP-9 was caused by Kisspeptin-10 and ERK inhibitor, shown by zymography. In human colorectal cancer tissues, the mRNA expression level of Kiss-1 had a negative correlation with Dukes staging, TNM staging, tumour size and lymph node involvement. Reduction of Kiss-1R was also linked to poor prognosis for the patients. The present study has presented evidence that Kiss-1 may be a putative metastasis suppressor molecule in human colorectal cancer.

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a cell–cell adhesion protein conferring heterotypic and homotypic interactions between cells of the same type and different types. It is aberrantly expressed in various cancer types and has been shown to be a regulator of cancer metastasis. In the present study, we investigated potential roles of ALCAM in the peritoneal transcoelomic metastasis in gastrointestinal cancers, a metastatic type commonly occurred in gastro-intestinal and gynaecological malignancies and resulting in poor clinical outcomes. Specifically, we studied whether ALCAM acts as both a ‘seed’ receptor in these tumour cells and a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. Gastric cancer and pancreatic cancer tissues with or without peritoneal metastasis were compared for their levels of ALCAM expression. The impact of ALCAM expression in these tumours was also correlated to the patients’ clinical outcomes, namely peritoneal metastasis-free survival. In addition, cancer cells of gastric and pancreatic origins were used to create cell models with decreased or increased levels of ALCAM expression by genetic knocking down or overexpression, respectively. Human peritoneal mesothelial cells were also genetically transfected to generate cell models with different profiles of ALCAM expression. These cell models were used in the tumour-mesothelial interaction assay to assess if and how the interaction was influenced by ALCAM. Both gastric and pancreatic tumour tissues from patients who developed peritoneal metastases had higher levels of ALCAM transcript than those without. Patients who had tumours with high levels of ALCAM had a much shorter peritoneal metastasis free survival compared with those who had low ALCAM expression (p = 0.006). ALCAM knockdown of the mesothelial cell line MET5A rendered the cells with reduced interaction with both gastric cancer cells and pancreatic cancer cells. Likewise, levels of ALCAM in both human gastric and pancreatic cancer cells were also a determining factor for their adhesiveness to mesothelial cells, a process that was likely to be triggered the phosphorylation of the SRC kinase. A soluble ALCAM (sALCAM) was found to be able to inhibit the adhesiveness between cancer cells and mesothelial cells, mechanistically behaving like a SRC kinase inhibitor. ALCAM is an indicator of peritoneal metastasis in both gastric and pancreatic cancer patients. It acts as not only a potential peritoneal ‘soil’ receptor of tumour seeding but also a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. These findings have an important therapeutic implication for treating peritoneal transcoelomic metastases.

Background: Synchronous dual-primary esophageal and gastric cancers (SEGC) are rare upper gastrointestinal malignancies presenting substantial challenges for prognostic assessment and individualized clinical evaluation. Conventional single-organ staging systems inadequately capture the cumulative tumor burden of synchronous cancers, limiting accurate prognostic assessment when tumors with different extents coexist. This study aimed to develop and externally validate a prognostic nomogram incorporating a Combined EG_Stage framework for exploratory risk stratification and post-treatment prognostic counseling in actively treated SEGC patients. Methods: A retrospective development cohort was assembled from a high-volume tertiary cancer center over 10 years (n = 46), with overall survival (OS) as the primary endpoint. A simplified Combined EG_Stage framework was developed to characterize cumulative anatomical tumor extent. Candidate prognostic predictors included age, treatment modality, and Combined EG_Stage. A multivariable Cox proportional hazards model was used to construct the nomogram. External validation used an independent cohort identified from 6,896 patients with multiple primary malignancies in the Surveillance, Epidemiology, and End Results (SEER) database, yielding 88 eligible patients. Model performance was assessed by discrimination, calibration, risk stratification, and decision curve analysis. Results: The final nomogram incorporated age, treatment modality, and Combined EG_Stage. Internal validation demonstrated satisfactory calibration across 1-, 3-, and 5-year horizons. In the external cohort, the model achieved a C-index of 0.681, with time-dependent AUC values of 0.616, 0.674, and 0.640 for 1-, 3-, and 5-year OS. Risk stratification significantly differentiated survival outcomes (median OS: 41 vs. 22 months; P = 0.022). Decision curve analysis suggested limited and exploratory net benefit across selected threshold probabilities, which should be interpreted cautiously given the small sample size. Conclusions: This study developed and externally evaluated a clinically interpretable but modestly discriminative prognostic nomogram for actively treated SEGC patients. By integrating age, treatment modality as a real-world prognostic indicator, and combined anatomical tumor burden, the model may support exploratory risk stratification in this rare malignancy. Given the limited sample size and only modest discriminative performance, the model should be considered hypothesis-generating rather than definitive, and further multicenter validation is required to assess its robustness and generalizability.