Objective:To evaluate the safety and feasibility of radical hepatectomy after conversion therapy in patients with initially unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 72 patients with initially unresectable advanced HCC admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University and the Department of Hepatobi-liary and Pancreatic Surgery, Henan Provincial People's Hospital from January 2020 to July 2024 were retrospectively collected, including 61 males and 11 females, aged (58.4±9.1) years. The clinicopathological data of the patients, such as tumor characteristics, conversion treatment regimens, perioperative data, and follow-up situations were analyzed to evaluate the therapeutic effect and safety.Results:Among the patients, there were five cases of China liver cancer staging Ⅰb, six cases of Ⅱa, 22 cases of Ⅱb, 32 cases of Ⅲa and sevene cases of Ⅲb. There were 53 patients scored as Child-Pugh A and 19 as Child-Pugh B. Conversion treatment fashion included immunotherapy combined with targeted therapy and immunotherapy plus targeted therapy combined with hepatic arterial chemoembolization or hepatic arteryinfusion chemotherapy. Liver resection after conversion therapy was as follows: 16 cases of right hemihepatectomy, 20 cases of left hemihepatectomy, 11 cases of mesohepatectomy, seven cases of right posterior hepatectomy, 1 case of caudate lobectomy, 17 cases of local resection. Postoperative pathology showed that there were 17 cases of pathologic complete response and 55 cases of pathologic partial response. One patient died of liver failure after surgery, while the rest had no major complications. The postoperative hospital stay was (13.1±5.1) d. The follow-up time was 21.5(10.2, 32.1) months. The multivariate Cox analysis demonstrated that pathologic partial response and adjuvant therapy duration shorter than 5 cycles were identified as independent risk factors-affecting both recurrence-free survival and overall survival in patients with HCC undergoing sequential surgery after conversion therapy (all P<0.05). Conclusion:Sequential surgical resection provides survival benefits for patients with initially unresectable and advanced HCC after conversion therapy, which is a safe and effective therapeutic strategy.

Objective·To investigate the expression of protein tyrosine phosphatase receptor type N(PTPRN)in lung adenocarcinoma and its potential molecular mechanisms in promoting lung adenocarcinoma metastasis.Methods·A highly bone-metastatic A549-BM cell line was established through multiple rounds of intracardiac injection.RNA sequencing(RNA-seq),combined with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,was performed to identify PTPRN as a key metastasis-related gene.Subsequently,The Cancer Genome Atlas(TCGA)database was utilized to evaluate PTPRN expression in patients with lung adenocarcinoma and its correlation with clinical prognosis.Co-expression analysis based on TCGA data was conducted to identify and analyze key genes co-expressed with PTPRN.Small interfering RNA(siRNA)targeting PTPRN(siPTPRN)was transfected into A549-BM cells,and Transwell assays were performed to assess its effects on cell migration and invasion.Western blotting was used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and the activation of the PI3K-AKT signaling pathway.siPTPRN-transfected A549-BM cells were injected into a mouse model via intracardiac injection,and in vivo metastasis was assessed.Additionally,multiple database analyses were integrated to predict BCL6 as an upstream transcription factor of PTPRN,and siBCL6 transfection experiments were performed to validate the regulatory effect of BCL6 on PTPRN expression.Results·RNA-seq and GO/KEGG enrichment analyses demonstrated that PTPRN was significantly upregulated in highly metastatic A549-BM cells and enriched in metastasis-associated pathways,including the PI3K-AKT signaling pathway and extracellular matrix(ECM)-receptor interactions.Analysis of the TCGA database further confirmed that PTPRN was highly expressed in lung adenocarcinoma patients and significantly associated with poor prognosis.Co-expression analysis based on TCGA data,combined with GO/KEGG enrichment analyses,revealed that PTPRN-associated genes were mainly enriched in biological processes such as neural signaling,endocrine regulation,cell communication,and ECM-receptor interactions.In vitro experiments demonstrated that siPTPRN transfection significantly inhibited the migration and invasion of A549-BM cells,accompanied by downregulation of EMT-related proteins and reduced activation of the PI3K-AKT signaling pathway.In vivo experiments further showed that PTPRN knockdown markedly suppressed the metastatic potential of A549-BM cells,confirming its pro-metastatic role.Additionally,siBCL6 transfection experiments demonstrated that BCL6 knockdown upregulated PTPRN expression.Conclusion·PTPRN is highly expressed in lung adenocarcinoma tissues and promotes tumor cell migration and metastasis by enhancing EMT and activating the PI3K-AKT signaling pathway.High PTPRN expression is significantly correlated with poor prognosis in lung adenocarcinoma patients,while PTPRN enhances lung adenocarcinoma cell invasiveness and metastatic potential.BCL6 may act as an upstream transcriptional regulator of PTPRN,influencing its expression levels.

Objective To investigate the clinical effectiveness and safety of apatinib mesylate combined with gemcitabine+cisplatin(GC)and camrelizumab in the treatment of advanced gallbladder cancer,and to provide evidence for the clinical treatment of patients with advanced gallbladder cancer.Methods A total of 75 patients with advanced gallbladder cancer admitted to Henan Provincial People's Hospital and The Affiliated Cancer Hospital of Zhengzhou University from January 2022 to December 2023 were retrospectively included.According to treatment plans,they were divided into study group(apatinib mesylate combined with GC+camrelizumab)and control group(GC+camrelizumab).The 1-year survival rate,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions were compared between the two groups.Inter-group comparisons were performed using the chi-square test/Fisher's exact test,the t-test,and the Mann-Whitney U test for categorical data,continuous data in normal distribution,and continuous data in non-normal distribution,respectively.The Kaplan-Meier survival curves were generated and compared using the log-rank test.Results The ORR and DCR of the study group were 35.0%and 80.0%,respectively,which were not significantly different from those of the control group(bothP>0.05).The 1-year survival rate of the study group differed significantly from that of the control group(45.0%vs 20.0%,P<0.05).The median PFS was 7.73(95%confidence interval[CI]:4.39-11.01)months in the study group and 4.17(95%CI:3.48-4.85)months in the control group,and the difference was statistically significant(P<0.01).The median OS was 11.77(95%CI:8.07-15.47)months in the study group and 7.97(95%CI:5.84-10.09)months in the control group,which were not statistically significant(P>0.05).Across all grades of adverse reactions,the study group showed significantly higher incidence rates of hand-foot syndrome(62.5%vs 34.3%,χ2=5.945,P<0.05)and elevated blood pressure(42.5%vs 20.0%,χ2=4.343,P<0.05)than the control group.There were no significant differences in the incidence rates of adverse reactions of grade Ⅲ or above between the two groups(all P>0.05).Conclusion Apatinib mesylate combined with GC+camrelizumab is superior to GC+camrelizumab in prolonging the PFS but not in terms of the OS,with controllable toxic side effects,which is a safe and effective treatment regimen.

Objective·To investigate the expression level of O-GlcNAc transferase(OGT)in non-small cell lung cancer(NSCLC)and its impact on lung cancer proliferation,as well as to explore the underlying mechanisms.Methods·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry(IHC).The dataset(GSE31210)from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis.siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells,followed by total RNA extraction and transcriptome sequencing.Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group,and Western blotting was used to validate the enrichment results.The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8(CCK-8)assay and colony formation assay,respectively.The impact of overexpressing downstream genes was also examined.Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth.Results·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues.Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression.Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.Western blotting showed that total extracellular regulated protein kinase 1/2(ERK1/2)levels remained unchanged in H460 and H1299 cells after OGT knockdown,while phosphorylated ERK1/2(p-ERK1/2)and its downstream proto-oncogene JUNB protein were markedly reduced.Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells,whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown.Notably,H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice.Conclusion·OGT is highly expressed in NSCLC and correlates with poor prognosis.Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro,and tumor growth in vivo.Mechanistically,OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis.

Objective·To investigate the expression of protein tyrosine phosphatase receptor type N(PTPRN)in lung adenocarcinoma and its potential molecular mechanisms in promoting lung adenocarcinoma metastasis.Methods·A highly bone-metastatic A549-BM cell line was established through multiple rounds of intracardiac injection.RNA sequencing(RNA-seq),combined with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,was performed to identify PTPRN as a key metastasis-related gene.Subsequently,The Cancer Genome Atlas(TCGA)database was utilized to evaluate PTPRN expression in patients with lung adenocarcinoma and its correlation with clinical prognosis.Co-expression analysis based on TCGA data was conducted to identify and analyze key genes co-expressed with PTPRN.Small interfering RNA(siRNA)targeting PTPRN(siPTPRN)was transfected into A549-BM cells,and Transwell assays were performed to assess its effects on cell migration and invasion.Western blotting was used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and the activation of the PI3K-AKT signaling pathway.siPTPRN-transfected A549-BM cells were injected into a mouse model via intracardiac injection,and in vivo metastasis was assessed.Additionally,multiple database analyses were integrated to predict BCL6 as an upstream transcription factor of PTPRN,and siBCL6 transfection experiments were performed to validate the regulatory effect of BCL6 on PTPRN expression.Results·RNA-seq and GO/KEGG enrichment analyses demonstrated that PTPRN was significantly upregulated in highly metastatic A549-BM cells and enriched in metastasis-associated pathways,including the PI3K-AKT signaling pathway and extracellular matrix(ECM)-receptor interactions.Analysis of the TCGA database further confirmed that PTPRN was highly expressed in lung adenocarcinoma patients and significantly associated with poor prognosis.Co-expression analysis based on TCGA data,combined with GO/KEGG enrichment analyses,revealed that PTPRN-associated genes were mainly enriched in biological processes such as neural signaling,endocrine regulation,cell communication,and ECM-receptor interactions.In vitro experiments demonstrated that siPTPRN transfection significantly inhibited the migration and invasion of A549-BM cells,accompanied by downregulation of EMT-related proteins and reduced activation of the PI3K-AKT signaling pathway.In vivo experiments further showed that PTPRN knockdown markedly suppressed the metastatic potential of A549-BM cells,confirming its pro-metastatic role.Additionally,siBCL6 transfection experiments demonstrated that BCL6 knockdown upregulated PTPRN expression.Conclusion·PTPRN is highly expressed in lung adenocarcinoma tissues and promotes tumor cell migration and metastasis by enhancing EMT and activating the PI3K-AKT signaling pathway.High PTPRN expression is significantly correlated with poor prognosis in lung adenocarcinoma patients,while PTPRN enhances lung adenocarcinoma cell invasiveness and metastatic potential.BCL6 may act as an upstream transcriptional regulator of PTPRN,influencing its expression levels.

Objective To investigate the clinical effectiveness and safety of apatinib mesylate combined with gemcitabine+cisplatin(GC)and camrelizumab in the treatment of advanced gallbladder cancer,and to provide evidence for the clinical treatment of patients with advanced gallbladder cancer.Methods A total of 75 patients with advanced gallbladder cancer admitted to Henan Provincial People's Hospital and The Affiliated Cancer Hospital of Zhengzhou University from January 2022 to December 2023 were retrospectively included.According to treatment plans,they were divided into study group(apatinib mesylate combined with GC+camrelizumab)and control group(GC+camrelizumab).The 1-year survival rate,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse reactions were compared between the two groups.Inter-group comparisons were performed using the chi-square test/Fisher's exact test,the t-test,and the Mann-Whitney U test for categorical data,continuous data in normal distribution,and continuous data in non-normal distribution,respectively.The Kaplan-Meier survival curves were generated and compared using the log-rank test.Results The ORR and DCR of the study group were 35.0%and 80.0%,respectively,which were not significantly different from those of the control group(bothP>0.05).The 1-year survival rate of the study group differed significantly from that of the control group(45.0%vs 20.0%,P<0.05).The median PFS was 7.73(95%confidence interval[CI]:4.39-11.01)months in the study group and 4.17(95%CI:3.48-4.85)months in the control group,and the difference was statistically significant(P<0.01).The median OS was 11.77(95%CI:8.07-15.47)months in the study group and 7.97(95%CI:5.84-10.09)months in the control group,which were not statistically significant(P>0.05).Across all grades of adverse reactions,the study group showed significantly higher incidence rates of hand-foot syndrome(62.5%vs 34.3%,χ2=5.945,P<0.05)and elevated blood pressure(42.5%vs 20.0%,χ2=4.343,P<0.05)than the control group.There were no significant differences in the incidence rates of adverse reactions of grade Ⅲ or above between the two groups(all P>0.05).Conclusion Apatinib mesylate combined with GC+camrelizumab is superior to GC+camrelizumab in prolonging the PFS but not in terms of the OS,with controllable toxic side effects,which is a safe and effective treatment regimen.

Objective·To investigate the expression level of O-GlcNAc transferase(OGT)in non-small cell lung cancer(NSCLC)and its impact on lung cancer proliferation,as well as to explore the underlying mechanisms.Methods·The expression of OGT in NSCLC tumors and adjacent normal tissues was detected by immunohistochemistry(IHC).The dataset(GSE31210)from the GEO database was analyzed to assess the correlation between OGT expression and NSCLC patient prognosis.siRNA transfection was performed to knock down OGT expression in H460 and H1299 cells,followed by total RNA extraction and transcriptome sequencing.Pathway enrichment analysis was conducted on differentially downregulated genes in the knockdown group compared with the control group,and Western blotting was used to validate the enrichment results.The effects of OGT knockdown on cell proliferation and colony formation in H460 and H1299 cells were evaluated using the cell counting kit-8(CCK-8)assay and colony formation assay,respectively.The impact of overexpressing downstream genes was also examined.Stable OGT-knockdown cell lines were generated using shRNA and subcutaneously inoculated into nude mice to monitor tumor growth.Results·IHC revealed that OGT expression was significantly upregulated in NSCLC tumor tissues compared to adjacent normal tissues.Patients with high OGT expression exhibited shorter survival times and poorer prognoses than those with low expression.Transcriptome sequencing demonstrated that genes downregulated after OGT knockdown were primarily enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.Western blotting showed that total extracellular regulated protein kinase 1/2(ERK1/2)levels remained unchanged in H460 and H1299 cells after OGT knockdown,while phosphorylated ERK1/2(p-ERK1/2)and its downstream proto-oncogene JUNB protein were markedly reduced.Suppression of OGT expression attenuated the proliferation rate and colony formation capacity of H460 and H1299 cells,whereas JUNB overexpression rescued the proliferation defects induced by OGT knockdown.Notably,H460 cells with stable OGT knockdown formed significantly smaller tumors in nude mice.Conclusion·OGT is highly expressed in NSCLC and correlates with poor prognosis.Knockdown of OGT inhibits NSCLC cell proliferation and clonogenicity in vitro,and tumor growth in vivo.Mechanistically,OGT appears to promote NSCLC progression by activating the ERK/JUNB signaling axis.

Objective:To evaluate the safety and feasibility of radical hepatectomy after conversion therapy in patients with initially unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 72 patients with initially unresectable advanced HCC admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University and the Department of Hepatobi-liary and Pancreatic Surgery, Henan Provincial People's Hospital from January 2020 to July 2024 were retrospectively collected, including 61 males and 11 females, aged (58.4±9.1) years. The clinicopathological data of the patients, such as tumor characteristics, conversion treatment regimens, perioperative data, and follow-up situations were analyzed to evaluate the therapeutic effect and safety.Results:Among the patients, there were five cases of China liver cancer staging Ⅰb, six cases of Ⅱa, 22 cases of Ⅱb, 32 cases of Ⅲa and sevene cases of Ⅲb. There were 53 patients scored as Child-Pugh A and 19 as Child-Pugh B. Conversion treatment fashion included immunotherapy combined with targeted therapy and immunotherapy plus targeted therapy combined with hepatic arterial chemoembolization or hepatic arteryinfusion chemotherapy. Liver resection after conversion therapy was as follows: 16 cases of right hemihepatectomy, 20 cases of left hemihepatectomy, 11 cases of mesohepatectomy, seven cases of right posterior hepatectomy, 1 case of caudate lobectomy, 17 cases of local resection. Postoperative pathology showed that there were 17 cases of pathologic complete response and 55 cases of pathologic partial response. One patient died of liver failure after surgery, while the rest had no major complications. The postoperative hospital stay was (13.1±5.1) d. The follow-up time was 21.5(10.2, 32.1) months. The multivariate Cox analysis demonstrated that pathologic partial response and adjuvant therapy duration shorter than 5 cycles were identified as independent risk factors-affecting both recurrence-free survival and overall survival in patients with HCC undergoing sequential surgery after conversion therapy (all P<0.05). Conclusion:Sequential surgical resection provides survival benefits for patients with initially unresectable and advanced HCC after conversion therapy, which is a safe and effective therapeutic strategy.

Objective:To explore the relevant risk factors and prognosis of patients with intrahepatic cholangiocarcinoma (ICC) who experienced recurrence within 6 months after surgeryMethods:This retrospective study included a total of 259 patients with ICC a treated at He'nan Provincial People's Hospital and He'nan Cancer Hospital from Jan 2018 to Jan 2020. The clinical and pathological data ,differences between the group with recurrence within 6 months and the group without recurrence within 6 months were compared using the chi-square test. Logistic regression analysis was used to determine the relevant risk factors for recurrence within 6 months. Kaplan-Meier method was used to construct survival and recurrence curves, and survival rates were calculated.Results:The overall survival and recurrence-free survival of patients in the group with recurrence within 6 months were significantly shorter. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery ( P<0.001). Conclusion:The patient population experiencing recurrence within 6 months after ICC surgery has an extremely poor prognosis and possesses a specific tumor microenvironment. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery.

Objective:To study the impact of patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent surgical resection with or without lymph node dissection (LND), negative or positive lymph node metastasis detected by LND, different extents of LND, and prognostic factors on long-term prognosis of these patients.Methods:The clinical data of 162 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to October 2019 and underwent surgical resection with postoperative histopathological results confirming ICC were retrospectively analyzed. According to the degree of LND, these patients were divided into three groups: the undissected group ( n=68), N0 dissected group (prophylactic dissection) ( n=41) and N1 dissected group (positive dissection, n=53). Of 94 patients who underwent LND, 23 patients underwernt the first station LND (the routine dissection group, n=23), and 71 patients underwent extended LND (the extended dissection group, n=71). The Kaplan-Meier method was used to construct survival curves. Cox regression analysis was used to detect independent factors affecting survival and long-term prognosis of patients. Results:In this study, there were 87 males and 75 females, with a median age of 60 years.The median survival time of these 162 ICC patients was 10 months. The cumulative survival rates at 1-, 3- and 5-year after surgery were 37.6%, 16.5% and 7.9%, respectively. The 1-, 3- and 5-year cumulative survival rates of the N0 dissection group were 52.1%, 31.7% and 25.4%, respectively, which were significantly better than those of the undissected group (34.2%, 12.7%, 3.4%), and the N1 dissection group (30.3%, 11.4%, 0) ( P<0.05). There were no significant differences in postoperative survival between the extended dissection group and the routine dissection group ( P>0.05). Preoperative CA19-9 >50 U/ml ( RR=1.425, 95% CI: 0.962-2.112), maximum tumor diameter > 5 cm ( RR=0.672, 95% CI: 0.456-0.989), without LND ( RR=1.715, 95% CI: 1.140-2.580), positive margin ( RR=0.591, 95% CI: 0.390-0.897), and without postoperative adjuvant therapy ( RR=0.663, 95% CI: 0.504-0.872) were independent risk factors affecting postoperative survival ( P<0.05). Conclusions:LND in ICC patients improved long-term survival outcomes. However, extended LND did not improve prognosis of these patients. The preoperative CA19-9 level, maximum tumor diameter, lymph node dissection, surgical margin status, and postoperative adjuvant therapy were independent risk factors affecting long-term prognosis of these patients.