ABSTRACT
OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.
Subject(s)
B7-H1 Antigen , Cancer-Associated Fibroblasts , Chemokine CXCL1 , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , B7-H1 Antigen/metabolism , Male , Female , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Middle Aged , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Chemokine CXCL1/metabolism , Cancer-Associated Fibroblasts/metabolism , Adult , Retrospective Studies , Neoplasm Metastasis , Prognosis , Phenotype , Biomarkers, Tumor/metabolism , Aged , Serine Endopeptidases/metabolism , Endopeptidases/metabolism , Membrane Proteins/metabolismABSTRACT
<p><b>OBJECTIVE</b>To study the clinical efficiency of metallic stent implantation in combination with three-dimensional conformal radiation therapy in the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus.</p><p><b>METHODS</b>22 cases of HCC patients with portal vein tumor thrombus were devided into 2 groups: 10 patients (group A) recieved stent implantation in combination with conformal radiation therapy, 12 patients (group B) recieved stent implantation and transcatheter arterial chemoembolization. The adverse reactions, and liver function before and after treatment were compared between the two groups. The stent patency rate at 4, 6 and 12 months and the survival rate at 3, 6 and 12 months were followed up. Comparison of liver function was analyzed by Wilcoxon signed rank test. Comparison of stent patency rate curves and survival curves was analyzed by Log rank test.</p><p><b>RESULTS</b>The portal vein catheterization was successful in all the patients. The stents were successfully implanted by transhepatic portal vein approach, and portal vein stenosis was re-opened. There was no abdominal hemorrhage in all the patients, but there were symptoms of abdominalgia, fever, nausea, vomiting and flatulence of varying degrees after interventional operation, and these symptoms were relieved by symptomatic treatment in one week. All patients in group A completed the treatment. I-II degree gastrointestinal tract reactions occurred in 3 cases, I-II degree myelosuppression occurred in 2 cases, and they were all completely relieved after treatment. The stent patency rate at 4, 6 and 12 months was 90%, 70%, 30% in group A; and 50%, 25% , 16.7% in group B (P < 0.05). The survival rate at 3, 6 and 12 months was 100%, 80% , 30% in group A and 91.7%, 41.7%, 16.7% in group B (P < 0.05).</p><p><b>CONCLUSION</b>Stent implantation combined with three-dimensional conformal radiation therapy is a good treatment for hepatocellular carcinoma with portal vein tumor thrombus and causes less damage to liver.</p>