ABSTRACT
BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.
Subject(s)
Lung Neoplasms , Lymphatic Metastasis , Small Cell Lung Carcinoma , Tomography, X-Ray Computed , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/epidemiology , Small Cell Lung Carcinoma/pathology , Male , Female , Middle Aged , Retrospective Studies , Aged , Lymphatic Metastasis/diagnostic imaging , Incidence , Tomography, X-Ray Computed/methods , Predictive Value of Tests , Contrast Media , Neoplasm Staging/methods , Adult , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Aged, 80 and over , RadiomicsABSTRACT
AIM: To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS: In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumor-adjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS: CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (χ2 = 6.669, P = 0.010; χ2 = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION: The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.
Subject(s)
Carcinoma/pathology , Chemokine CXCL12/metabolism , Liver Neoplasms/pathology , Lymph Nodes/pathology , Receptors, CXCR/metabolism , Stomach Neoplasms/pathology , Aged , Carcinoma/secondary , Cell Line, Tumor , Cell Proliferation , Female , Gene Knockdown Techniques , Humans , Immunohistochemistry , Liver/pathology , Liver Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , RNA Interference , RNA, Small Interfering/metabolism , Receptors, CXCR/genetics , Signal Transduction , Stomach/pathologyABSTRACT
AIM: To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography (CT) perfusion of rabbit VX2 tumor. METHODS: Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential (120 kVp) protocol with 350 mgI/mL contrast medium and filtered back projection, and a low tube potential (80 kVp) protocol with 270 mgI/mL contrast medium with iterative reconstruction. Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor. Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated. RESULTS: A 38% reduction in contrast medium dose (360.1 ± 13.3 mgI/kg vs 583.5 ± 21.5 mgI/kg, P < 0.001) and a 73% decrease in radiation dose (1898.5 mGy ⢠cm vs 6951.8 mGy ⢠cm) were observed. Interestingly, there was a strong positive correlation in hepatic arterial perfusion (r = 0.907, P < 0.001; r = 0.879, P < 0.001), hepatic portal perfusion (r = 0.819, P = 0.002; r = 0.831, P = 0.002), and hepatic blood flow (r = 0.945, P < 0.001; r = 0.930, P < 0.001) as well as a moderate correlation in hepatic perfusion index (r = 0.736, P = 0.01; r = 0.636, P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor. These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumor-to-liver CNR during arterial and portal venous phases (5.63 ± 2.38 vs 6.16 ± 2.60, P = 0.814; 4.60 ± 1.27 vs 5.11 ± 1.74, P = 0.587). CONCLUSION: Compared with the conventional protocol, low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.
Subject(s)
Contrast Media/administration & dosage , Iohexol/administration & dosage , Liver Neoplasms, Experimental/blood supply , Liver Neoplasms, Experimental/diagnostic imaging , Multidetector Computed Tomography , Perfusion Imaging/methods , Radiation Dosage , Animals , Blood Flow Velocity , Feasibility Studies , Liver Neoplasms, Experimental/pathology , Microvessels/diagnostic imaging , Microvessels/physiopathology , Predictive Value of Tests , Rabbits , Radiographic Image Interpretation, Computer-Assisted , Regional Blood FlowABSTRACT
AIM: To prepare the high titer and specific anti-serum against mouse Foxp3 and then use them to identify Foxp3 expression in normal mouse tissues. METHODS: The Foxp3 fragment was amplified by polymerase chain reactions(PCR) and cloned into the prokaryotic expression vector pGEX-6p-2. The recombinant plasmid pGEX-6p-2/Foxp3 was transformed into E.coli BL21(DE3) to be expressed. The expressed fusion protein GST-Foxp3 was analyzed by SDS-PAGE and Western blot. The polyclonal clanti-serum was obtained by immunizing New Zealand rabbits with the purified fusion protein as antigen. The Foxp3 expression in normal mouse tissues was detected by Western blot with the anti-serum. RESULTS: The expressed products were analyzed by SDS-PAGE and Western blot. The results showed that the molecular weight of the expressed protein was about 45 000. The titer of the anti-serum was above 1:12 800. We observed that the anti-serum could recognize Foxp3 protein expressed in NIH3T3 cells by immunoblotting. Western blot results showed that the Foxp3 protein was expressed highly in spleen, thymus and lymph nodes, less expressed in stomach, but not expressed in skeletal muscle and adipose tissue. CONCLUSION: High titer antiserum against mouse Foxp3 is produced and can be used to identify the Foxp3 expression in normal mouse tissues.