BackgroundLymph node metastasis (LNM) has a significant impact on the prognosis of patients with early gastric cancer (EGC). Our aim was to identify the independent risk factors for LNM and construct nomograms for male and female EGC patients, respectively.MethodsClinicopathological data of 1,742 EGC patients who underwent radical gastrectomy and lymphadenectomy in the First Affiliated Hospital, Second Affiliated Hospital, and Fourth Affiliated Hospital of Anhui Medical University between November 2011 and April 2021 were collected and analyzed retrospectively. Male and female patients from the First Affiliated Hospital of Anhui Medical University were assigned to training sets and then from the Second and Fourth Affiliated Hospitals of Anhui Medical University were enrolled in validation sets. Based on independent risk factors for LNM in male and female EGC patients from the training sets, the nomograms were established respectively, which was also verified by internal validation from the training sets and external validation from the validation sets.ResultsTumor size (odd ratio (OR): 1.386, p = 0.030), depth of invasion (OR: 0.306, p = 0.001), Lauren type (OR: 2.816, p = 0.000), lymphovascular invasion (LVI) (OR: 0.160, p = 0.000), and menopause (OR: 0.296, p = 0.009) were independent risk factors for female EGC patients. For male EGC patients, tumor size (OR: 1.298, p = 0.007), depth of invasion (OR: 0.257, p = 0.000), tumor location (OR: 0.659, p = 0.002), WHO type (OR: 1.419, p = 0.001), Lauren type (OR: 3.099, p = 0.000), and LVI (OR: 0.131, p = 0.000) were independent risk factors. Moreover, nomograms were established to predict the risk of LNM for female and male EGC patients, respectively. The area under the ROC curve of nomograms for female and male training sets were 87.7% (95% confidence interval (CI): 0.8397–0.914) and 94.8% (95% CI: 0.9273–0.9695), respectively. For the validation set, they were 92.4% (95% CI: 0.7979–1) and 93.4% (95% CI: 0.8928–0.9755), respectively. Additionally, the calibration curves showed good agreements between the bias-corrected prediction and the ideal reference line for both training sets and validation sets in female and male EGC patients.ConclusionsNomograms based on risk factors for LNM in male and female EGC patients may provide new insights into the selection of appropriate treatment methods.

BACKGROUND Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated. AIM To investigate whether and how IL-34 affects the proliferation of GC cells and EMT. METHODS Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting. RESULTS Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice. CONCLUSION IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.