ObjectiveTo investigate the predictive value of thyroid transcription factor-1 (TTF-1) in the treatment of advanced lung adenocarcinoma with different chemotherapy regimens.MethodsA total of 126 patients with advanced lung cancer were divided into three groups according to the chemotherapy regimen, namely a pemetrexed+nedaplatin group (PEM+NDP group), a pemetrexed+cisplatin/carboplatin group (PEM+DDP/CBP group) and a third-generation (3G) chemotherapy+cisplatin/carboplatin group (3G agent+DDP/CBP group). The predictive value of TTF-1 in the above three treatment regimens was analyzed. The patients were followed up by telephone or outpatient visit until April 2017.ResultsThere were no significant differences in disease control rate or objective response rate between the three different chemotherapy regimens (all P>0.05). The survival rate of PEM+NDP group was significantly higher than that of PEM+DDP/CBP group and 3G agent+DDP/CBP group (9.68%vs. 5.56% and 6.80%, both P<0.05). ECOG score and brain metastasis were independent risk factors for the prognosis of chemotherapy regimens. TTF-1 was an independent risk factor for PEM+NDP therapy.ConclusionTTF-1 is an independent risk factor for PEM+NDP chemotherapy, but not for 3G agent + DDP/CBP or PEM+DDP/CBP regimens.
Objective To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. MethodsThe patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.
ObjectiveTo explore the expressions of glucose regulated protein (GRP) 78 and GRP94 in rectal adenocarcinoma and their clinical significances. MethodsIn 45 paraffin-embedded sections of rectal adenocarcinoma tissues and adjacent normal tissues, the expressions of GRP78 and GRP94 were examined by EnVisionTM. ResultsThe positive rates of GRP78 and GRP94 protein expression in the rectal adenocarcinoma tissues were 53.33% (24/45) and 53.33% (24/45), while those in the adjacent normal tissues were 13.33% (6/45) and 15.56% (7/45), respectively. There was a statistical significance of the expression of GRP78 or GRP94 between the tumor tissues and the adjacent normal tissues (all P < 0.001), and it was found that the positive expression rates were relevant to the extent of differentiation, Dukes stage, and lymph node metastasis of cancer (all P < 0.05), but not to the patient's sex, age, and size of tumor (all P > 0.05). And there was a statistical significance in Spearman method about the rate of positive expression between GRP78 and GRP94 (rs=0.464, P < 0.01). ConclusionGRP78 and GRP94 protein is highly expressed in rectal adenocarcinoma tissue, related to its metastasis and invasion, might be used as a useful indicator to judge the malignant degree.
ObjectiveTo investigate the risk factors for lymph node metastasis in resectable lung adenocarcinoma by combining spatial location, clinical, and imaging features, and to construct a lymph node metastasis prediction model. MethodsA retrospective study on patients who underwent chest computed tomography (CT) at the First Affiliated Hospital of Nanjing Medical University from June 2016 to June 2020 and were surgically confirmed to have invasive lung adenocarcinoma with or without lymph node metastasis was conducted. Patients were divided into a positive group and a negative group based on the presence or absence of lymph node metastasis. Clinical and imaging data of the patients were collected, and the independent risk factors for lymph node metastasis in resectable lung adenocarcinoma were analyzed using univariate and multivariate logistic regression. A combined spatial location-clinical-imaging feature prediction model for lymph node metastasis was established and compared with the traditional lymph node metastasis prediction model that does not include spatial location features. ResultsA total of 611 patients were included, with 333 in the positive group, including 172 males and 161 females, with an average age of (58.9±9.7) years; and 278 in the negative group, including 127 males and 151 females, with an average age of (60.1±11.4) years. Univariate and multivariate logistic regression analyses showed that the spatial relationship of the lesion to the lung hilum, nodule type, pleural changes, and serum carcinoembryonic antigen (CEA) levels were independent risk factors for lymph node metastasis. Based on this, the combined spatial location-clinical-imaging feature prediction model had a sensitivity of 91.67%, specificity of 74.05%, accuracy of 87.88%, and area under the curve (AUC) of 0.885. The traditional lymph node metastasis prediction model, which did not include spatial location features, had a sensitivity of 76.40%, specificity of 72.10%, accuracy of 53.86%, and AUC of 0.827. The difference in AUC between the two prediction methods was statistically significant (P=0.026). Compared with the traditional prediction model, the predictive performance of the combined spatial location-clinical-imaging feature prediction model was significantly improved. ConclusionIn patients with resectable lung adenocarcinoma, those with basal spatial location, solid density, pleural changes with wide base depression, and elevated serum CEA levels have a higher risk of lymph node metastasis.
ObjectiveTo investigate the radiological and clinicopathological factors affecting the postoperative recurrence of early lung adenocarcinoma with micropapillary/solid structure.MethodsA total of 198 patients undergoing surgical resection for early stage lung adenocarcinoma in the First Affiliated Hospital of Nanjing Medical University from January 2016 to August 2019 were enrolled, including 100 males and 98 females, aged 28-82 (53.5±9.5) years. All patients were allocated to a recurrence group (n=21) and a non-recurrence group (n=177) according to postoperative recurrence status. Correlations of imaging and clinical features and clinical outcomes were analyzed to determine prognostic significance.ResultsThe mean follow-up time was 27.0±11.2 months. There was no statistical difference in the imaging features of tumor maximum diameter in mediastinal window (P=0.014), C/T ratio (P=0.001), bronchial positive sign (P=0.015), pathological features of vascular invasion (P=0.024) and postoperative chemotherapy (P<0.001) between the two groups. In multivariate analysis, vascular invasion was the only independent prognostic factor (OR=0.146, P=0.047).ConclusionVascular invasion is an independent risk factor for postoperative recurrence of early-stage lung adenocarcinoma with micropapillary/solid structure.
ObjectiveTo analyze the expression of cold-induced RNA-binding protein (CIRBP) in lung adenocarcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for lung adenocarcinoma.MethodsThe CIRBP gene expression data and patient clinical information data in lung adenocarcinoma tissues and adjacent tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression of CIRBP in lung adenocarcinoma was analyzed. Furthermore, its relationship with clinicopathological features and prognosis in patients with lung adenocarcinoma was analyzed. GO and KEGG enrichment analysis were carried out for the screened genes. The CIRBP protein interaction network was constructed by STRING, and the correlation analysis was carried out using the GEPIA online website.ResultsThe expression level of CIRBP gene in lung adenocarcinoma tissues was significantly lower than that in adjacent tissues (P<0.01), and its expression level was correlated with T stage and N stage in clinicopathological features. The prognosis of patients with high CIRBP expression in lung adenocarcinoma was significantly better than that with low CIRBP expression. Univariate and multivariate Cox regression analysis showed that CIRBP was an independent prognostic factor in patients with lung adenocarcinoma. GO functional annotation showed its enrichment in organelle fission, nuclear fission, chromosome separation, and DNA replication, etc. KEGG analysis showed that it was mainly involved in cell cycle and DNA replication. Protein interaction network and GEPIA online analysis showed that the expression level of CIRBP was negatively correlated with the expression level of cyclin B2.ConclusionCIRBP gene is down-regulated in lung adenocarcinoma tissues, and its expression level is closely related to patient prognosis. CIRBP gene may be a potential therapeutic target and prognostic marker for lung adenocarcinoma.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.
Objective To explore the effect on apoptotic genes of pancreatic adenocarcinoma cell BxPC-3 from subcutaneous transplantation tumor in nude mice induced by 5-FU and sulfasalazine (SZ).Methods Changes of apoptosis-related genes 〔bcl-2, cyclinD1, Bax and NF-κB (p65)〕 in subcutaneous transplantation tumor treated by 5-FU, SZ alone or both at the levels of mRNA and protein were measured by RT-PCR and Western blot. Results NF-κB (p65) at mRNA relative content and protein expression in subcutaneously heterotopic transplantation tumor treated by 5-FU (7.5, 15 mg/kg), SZ (10, 20 mg/kg) alone or both showed significant difference, except for two subsets in SZ group, respectively, in comparison with each control group (P＜0.01). Meanwhile bcl-2 and cyclinD1 at the levels of mRNA and protein, and Bax protein level were significantly different from each control group (P＜0.01). The above-mentioned indexes were show obvious interaction of both by multiple factor analysis of variance. Conclusion Up-regulated level of Bax, down-regulated levels of bcl-2, cyclinD1 and NF-κB (p65) might be one of apoptotic mechanisms that SZ synergistically enhanced apoptotic effect on pancreatic adenocarcinoma cell BxPC-3 of subcutaneous transplantation tumor in nude mice induced by 5-FU.
Objective To identify and isolate the variant gene associated with gastric adenocarcinoma and clone the fragment of variant gene.Methods By arbitrarily primer polymerase chain reaction (AP-PCR), DNA samples from 5 matched gastric adenocarcinoma and non-tumor gastric tissues were analysed. Results The produced AP-PCR profiles were different in each matched gastric adenocarcinoma and non-tumor gastric tissue. One differentiated amplified DNA fragments PW2.2 from a matched gastric adenocarcinoma were cloned. The result of Southern blot hybridization with PW2.2 as a probe showing that this fragment was also found in some other gastric adenocarcinoma samples. Conclusion AP-PCR fingerprinting assay can be used to identify and clone the variant genes associated with gastric adenocarcinoma.
To study the expressions of CA19-9 and CA125 and their clinicopathologic significancesin gallbladder adenocarcinoma , pericancerous tissues and chronic cholecystitis. Methods EnVisionTM immunohistochemist ry was used for assaying the expressive levels of CA1929 and CA125 in the routinely paraffin2embedded sections of specimens f rom gallbladder adenocarcinoma ( n = 108) , pericancerous tissues ( n = 46) , and chronic cholecystitis ( n = 35) . Results The positive rates of CA19-9 and CA125 were significantly higher in gallbladder adenocarcinoma ( 49. 1 % , 51. 9 %) than those in pericancerous tissues ( 26. 1 % , 15. 2 %) and chronic cholecystitis(14. 3 % , 5. 7 %) , respectively ( Plt; 0. 01) . The positive rates of CA19-9 and CA125 were significantly lower in thecases of adenomatous canceration , maximal diameter lt; 2 cm , no-metastasis of lymph node and no-invasion of regional tissues than those in the ones of low-differentiated adenocarcinoma , maximal diameter ≥2 cm , metastasis oflymph node and invasion of regional tissues ( Plt; 0. 05 , Plt; 0. 01 ) . The consistence of CA19-9 and CA125 expressivelevels was found in gallbladder adenocarcinoma (χ2 = 44. 69 , Plt; 0. 01) . Conclusion The expressions of CA19-9 andCA125 may be important tumor markers to reflect the carcinogenesis , progression , biological behaviors and prognosis of gallbladder adenocarcinoma.