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BRAF V600E Mutation as a Predictive Factor of Anti-EGFR Monoclonal Antibodies Therapeutic Effects in Metastatic Colorectal Cancer: a Meta-analysis

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Chinese Medical Sciences Journal 2014年第4期29卷 197-203页

作者： qi Wang Wei-guo Hu qi-bin song Jia Wei Department of Oncology Renmin Hospital of Wuhan University

Objective To investigate the correlation between BRAF V600 E mutation and anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) therapeutic effects in metastatic colorectal cancer. Methods Studies were included into meta-analysis to investigate the association between BRAF V600 E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR Mo Abs. Results A total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate(ORR), progression-free survival(PFS) and overall survival(OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27(95% CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR Mo Abs(hazard ratio=2.78, 95% CI=1.62-4.76; hazard ratio=2.54, 95% CI=1.93-3.32). Conclusion BRAF V600 E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR Mo Abs.

关键词： colorectal neoplasms BRAF meta-analysis

Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients

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Current Medical Science 2022年第6期42卷 1273-1284页

作者： Jie WU Lan LI Hao ZHONG Hao-han ZHANG Jing LI Hui-bo ZHANG Ya-qi ZHAO bin XU qi-bin song Cancer Center Renmin Hospital of Wuhan UniversityWuhan430030China Department of Bioinformatics Wissenschaftszentrum WeihenstephanTechnical University of MunichFreising85354Germany

Objective This study aims to investigate the expression,prognostic value,and function of kinesin superfamily 4A(KIF4A)in cervical *** Cervical cancer cell lines(Hela and SiHa)and TCGA data were used for experimental and bioinformatic *** survival(OS)and progression free survival(PFS)were compared between patients with high or low KIF4A *** number variation(CNV)and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered *** function of KIF4A was also explored based on transcriptome analysis and validated by experimental *** and immunotherapeutic benefits were inferred using multiple reference databases and *** Patients with high KIF4A expression had better OS and ***4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer *** CNV load was observed in patients with low KIF4A expression,while the group with low KIF4A expression displayed more significantly altered sites.A total of 13 genes were found to mutate more in the low KIF4A expression group,including NOTCH1 and *** analysis revealed that low KIF4A expression may indicate an immune escape phenotype,and patients in this group may benefit more from *** respect to chemotherapy,cisplatin and gemcitabine may respond better in patients with high KIF4A expression,while 5-fluorouracil *** be responded better in patients with low KIF4A expression Conclusion KIF4A is a tumor suppressor gene in cervical cancer,and it can be used as a prognostic and therapeutic biomarker in cervical cancer.

关键词： kinesin superfamily 4A cervical cancer prognosis chemotherapy immunotherapy

Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages Ⅰ and Ⅱ gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第1期12卷 101-112页

作者： Yu-Xin Chu Hong-Yun Gong qin-Yong Hu qi-bin song Department of Oncology (Division Ⅰ) Cancer CenterRenmin Hospital of Wuhan University

BACKGROUND Primary gastric adenosquamous carcinoma(ASC)is an exceedingly rare histological *** signet ring cell carcinoma(SRC)is a unique subtype with distinct tumor biology and clinical *** prognosis of gastric ASC vs SRC has not been well established to *** hypothesized that further knowledge about these distinct cancers would improve the clinical management of such *** To investigate the clinicopathological characteristics and prognosis of gastric ASC vs *** A cohort of gastric cancer patients was retrospectively collected from the Surveillance,epidemiology,and end results program *** 1:4 propensity score matching was performed among this *** clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive ***-Meier method was utilized to calculate the median survival of the two groups of *** proportional hazard regression models were used to identify prognostic *** Totally 6063 patients with gastric ASC or SRC were identified.A cohort of 465 patients was recruited to the matched population,including 370 patients with SRC and 95 patients with *** ASC showed an inferior prognosis to SRC after propensity score *** the post-matching cohort,the median cancer specific survival was 13.0(9.7-16.3)mo in the ASC group vs 20.0(15.7-24.3)mo in the SRC group,and the median overall survival had a similar trend(P<0.05).ASC and higher tumor-node-metastasis stage were independently associated with a poor survival,while radiotherapy and surgery were independent protective factors for improved *** survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II *** ASC may have an inferior prognosis to SRC in patients with stages I and II gastric *** study supports radiotherapy and surgery for the future management of this clinically rare entity.

关键词： Adenosquamous carcinoma Signet ring cell carcinoma Surveillance,Epidemiology,and End results Propensity score matching Prognosis Survival

A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk

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Chinese Journal of Cancer Research 2014年第3期26卷 255-267页

作者： qi-bin song qi Wang Wei-Guo Hu Department of Oncology Renmin Hospital of Wuhan University

Objectives： To investigate the correlation between glutathione S-transferase P1 （GSTP1） Ilel05Val polymorphism and colorectal cancer （CRC） risk. Methods： Studies were identified to investigate the association between GSTP1 Ilel05Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios （OR） and 95% confidence intervals （95 % CI） were used to measure GSTP 1 Ile 105Val polymorphisms and CRC risk. Results： A total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that lie 105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ilel05Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium （HWE） in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results. Conclusions： GSTP1 Ilel05Val might be associated with increased risk of CRC. However, more high- quality case-control studies should be performed to confirm the authenticity of our conclusion.

关键词： Colorectal neoplasm glutathione S-transferase P 1 (GSTP 1) polymorphisms

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes

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Current Medical Science 2023年第6期43卷 1133-1150页

作者： Ya-qi ZHAO Hao-han ZHANG Jie WU Lan LI Jing LI Hao ZHONG Yan JIN Tian-yu LEI Xin-yi ZHAO bin XU qi-bin song Jie HE Cancer Center Renmin Hospital of Wuhan UniversityWuhan430060China Department of Medical Oncology First Affiliated Hospital of Kunming Medical UniversityKunming650000China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100032China

Objective Pseudogenes are initially regarded as nonfunctional genomic sequences,but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional *** receptor family 7 subfamily E member 47 pseudogene(OR7E47P)is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment(TME)of lung adenocarcinoma(LUAD).This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma(LUSC).Methods Clinical and molecular information from The Cancer Genome Atlas(TCGA)LUSC cohort was used to identify OR7E47P-related immune genes(ORIGs)by weighted gene correlation network analysis(WGCNA).Based on the ORIGs,2 OR7E47P clusters were identified using non-negative matrix factorization(NMF)clustering,and the stability of the clustering was tested by an extreme gradient boosting classifier(XGBoost).LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model(ORPScore)for *** Botling cohorts and 8 immunotherapy cohorts(the Samstein,Braun,Jung,Gide,IMvigor210,Lauss,Van Allen,and Cho cohorts)were included as independent validation *** OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC.A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters(Cluster 1 and Cluster 2)with distinct immune,mutation,and stromal *** to Cluster 1,Cluster 2 had more infiltration by immune and stromal cells,lower mutation rates of driver genes,and higher expression of immune-related *** clustering performed well in the internal and 5 external validation *** on the 7 ORIGs(HOPX,STX2,WFS,DUSP22,SLFN13,GGCT,and CCSER2),the ORPScore was constructed to predict the prognosis and the treatment *** addition,the ORPScore was a bette

关键词： pseudogene olfactory receptor family 7 subfamily E member 47 pseudogene-related immune gene tumor microenvironment immunotherapy lung squamous cell carcinoma

Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment

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Current Medical Science 2023年第4期43卷 631-646页

作者： Jun-ju HE qing-qing LI Chen ZHAO Jin ZHOU Jie WU Hui-bo ZHANG Ya-qi ZHAO Hao-han ZHANG Tian-yu LEI Xin-yi ZHAO Zuo YOU qi-bin song bin XU Cancer Center Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Traditional Chinese Medicine Xianfeng County People's HospitalEnshi 445000China

Cancer treatment has evolved rapidly due to major advances in tumor immunity ***,due to the complexity,heterogeneity,and immunosuppressive microenvir-onment of tumors,the overall efficacy of immunotherapy is only 20%.In recent years,nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility,precise targeting,and controlled drug ***,the clinical application of nanomedicine also faces many problems concerning biological safety,and the synergistic mechanism of nano-drugs with immunity remains to be *** study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive ***,the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

关键词： nanotherapy tumor microenvironment immunotherapy

Local Extrema of Periodic Function’s Wavelet Transform

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Wuhan University Journal of Natural Sciences 2005年第6期10卷 949-952页

作者： FAN qi-bin song Xiao-yan School of Mathematics and Statistics Wuhan University Wuhan 430072 Hubei China

The theory of detecling ridges in the modulus of the continuous wavelet transform is presented as well as reconstructing signal by using information on ridges,To periodic signal we suppose Morlet wavelet as basic wavelet, and research the local extreme point and extrema of the wavelet transform on periodic function for the collection of signal＇ s instantaneous amplitude and period.

关键词： extrema periodic function wavelet transform time-frequency analysis

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo qi Han Tang Jianian Hu Siying Kang song qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian Ding Chun Chen Heng Zhao bin Dai Lei Ye Tao song Shuai Huang Jia Wang Tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2