ABSTRACT
Objective:To explore the alteration of JAK2/STAT3 pathway after carbon ion ( 12C 6+) irradiation and the difference in the infiltration of CD8 + T cells in lung cancer regulated by downstream protein FOXP3. Methods:Significantly altered JAK2/STAT3 pathway and related differentially-expressed genes and proteins such as FOXP3 in lung cancer after carbon ion irradiation were screened based on RNA sequencing analysis in the Lewis tumor model of C57BL/6 mice. The correlation between FOXP3 and major immune cell infiltration in the immune microenvironment of lung cancer was analyzed using the ssGSEA immune infiltration algorithm in the R software "GSVA" and CD8 + T cell infiltration in the immune microenvironment of lung cancer was evaluated based on the carbon ion combined with STAT3 inhibition pathway (niclosamide). Results:The JAK2/STAT3 pathway was inhibited and the expression of related genes and proteins was downregulated in lung cancer after carbon ion irradiation. Immune scoring based on the ssGSEA algorithm showed that FOXP3 expression was significantly negatively correlated with CD8 + T cell infiltration in the immune microenvironment of lung cancer. The role of targeting the JAK2/STAT3 pathway in increasing CD8 + T cell infiltration in lung cancer was further clarified by carbon ion irradiation combined with STAT3 inhibition (niclosamide). Conclusion:Carbon ion irradiation ( 12C 6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.
ABSTRACT
Objective: To detect the expression of P53, human epidermal growth factor receptor-2 (HER-2), and tumor endothelial marker 1 (TEM1) in gastric cancer tissues, analyze their correlation with clinical efficacy, and explore their potential roles as biomarkers for neoadjuvant chemotherapy. Methods: Sixty-three patients with gastric cancer who underwent fluorouracil-based neoadjuvant che-motherapy in The First Hospital of Lanzhou University from May 2015 to May 2017 were enrolled. Using immunohistochemistry, the expression of P53, Her2, and TEM1 was detected in 63 gastric cancer specimens before neoadjuvant chemotherapy. The efficacy of neoadjuvant chemotherapy was assessed by imaging. The relationship between the expression of P53, HER-2, and TEM1 and the effi-cacy of neoadjuvant chemotherapy was analyzed. Results: The total effective rate of neoadjuvant chemotherapy in 63 patients with advanced gastric cancer was 69.8%, with 2, 7, and 35 patients achieving complete remission, partial remission, and stable disease, re-spectively. Disease progression was noted in 19 patients. Univariate analysis revealed that patients positive for TEM1 and having high T stage had a poor response to neoadjuvant chemotherapy (P<0.05); furthermore, location, differentiation, and size of tumor; P53 posi-tivity (P=0.488); and Her-2 positivity (P=0.106) were not associated with the efficacy of neoadjuvant chemotherapy for gastric cancer. Multivariate analysis revealed that TEM1 positivity and a higher T stage could be factors that predicted the response to neoadjuvant chemotherapy in patients with advanced gastric cancer. Conclusions: TEM1, as a marker of tumor stroma, may be an important molec-ular biological indicator that predicts the poor response to neoadjuvant chemotherapy in patients with gastric cancer.