Oral mucositis(OM)is a prevalent and debilitating cancer therapy-related side effect that significantly impairs the quality of life of patients with cancer.In this article,we review anticancer treatment-induced OM,elucidate the underlying pathophysiological mechanisms,and discuss various preventive and therapeutic strategies,including basic oral care,nutritional supplements,cryotherapy,photobiomodula-tion therapy,and pharmacological interventions.While single modality treatments might yield certain clinical benefits,an integrated ap-proach,combining prophylactic measures with multimodal therapies,could more effectively reduce OM incidence and severity,promote mucosal healing,minimize the risk of serious complications,and enhance patient outcomes.

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 explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.

The rapid development of immunotherapy has changed the treatment pattern of gastric cancer surgery, constantly advancing from the battlefield of advanced gastric cancer treatment to neoadjuvant therapy. The combination of immunotherapy and chemotherapy has become a new trend in the treatment of locally advanced gastric cancer. This change has prompted us to re-examine the concept of traditional radical surgery for gastric cancer, especially for lymph node dissection, it presents new challenges. As the core site of immune response, lymph node dissection strategy has become one of the key factors affecting the overall efficacy of gastric cancer, and it urgently needs to be re optimized and evaluated in the wave of immunotherapy. Thus, a more precise and personalized new paradigm for radical gastric cancer surgery can be established, ultimately achieving multiple improvements in short-term and long-term efficacy, as well as quality of life.

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 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 explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.

The rapid development of immunotherapy has changed the treatment pattern of gastric cancer surgery, constantly advancing from the battlefield of advanced gastric cancer treatment to neoadjuvant therapy. The combination of immunotherapy and chemotherapy has become a new trend in the treatment of locally advanced gastric cancer. This change has prompted us to re-examine the concept of traditional radical surgery for gastric cancer, especially for lymph node dissection, it presents new challenges. As the core site of immune response, lymph node dissection strategy has become one of the key factors affecting the overall efficacy of gastric cancer, and it urgently needs to be re optimized and evaluated in the wave of immunotherapy. Thus, a more precise and personalized new paradigm for radical gastric cancer surgery can be established, ultimately achieving multiple improvements in short-term and long-term efficacy, as well as quality of life.

Oral mucositis(OM)is a prevalent and debilitating cancer therapy-related side effect that significantly impairs the quality of life of patients with cancer.In this article,we review anticancer treatment-induced OM,elucidate the underlying pathophysiological mechanisms,and discuss various preventive and therapeutic strategies,including basic oral care,nutritional supplements,cryotherapy,photobiomodula-tion therapy,and pharmacological interventions.While single modality treatments might yield certain clinical benefits,an integrated ap-proach,combining prophylactic measures with multimodal therapies,could more effectively reduce OM incidence and severity,promote mucosal healing,minimize the risk of serious complications,and enhance patient outcomes.