1.Evaluation of high-risk HPV genotyping detection in cervical cancer screening based on a prospective cohort study
Hong WANG ; Yin LIU ; Huifang XU ; Peipei CHEN ; Xingyuan SUN ; Mengjie LI ; Peiyao LI ; Kunyao LI ; Liyang ZHENG ; Shuzheng LIU ; Xibin SUN ; Youlin QIAO ; Shaokai ZHANG
Chinese Journal of Oncology 2025;47(5):435-442
Objective:To evaluate the clinical performance of high-risk human papillomavirus (HR-HPV) genotyping in cervical cancer screening.Methods:Between June and July 2017, a prospective cervical cancer screening cohort was established in Xiaye Town, Jiyuan City, Henan Province, China by recruiting 3 254 women aged 21 to 64 years. At baseline screening, cervical exfoliated cell specimens were collected for HR-HPV genotyping and liquid-based cytology testing. Follow-ups were conducted over a 3-year period, with cytology testing in the first and second years and both HR-HPV genotyping and cytology testing in the third year. Women meeting the referral criteria were referred for colposcopy, with cervical biopsy and histopathological diagnosis performed as necessary. The endpoint was defined as cervical intraepithelial neoplasia grade 2 (CIN2) or higher confirmed by histopathological diagnosis. The sensitivity and specificity for detecting CIN2 or higher lesions of HR-HPV genotyping were calculated, as well as the cumulative risk of developing CIN2 or higher lesions over the 4-year study period in women with different baseline HR-HPV genotyping results.Results:A total of 2 741 women were included in the statistical analysis. Baseline HR-HPV genotyping detected 453 HR-HPV positive cases (16.53%), including 98 HPV 16/18 positive cases (3.58%) and 355 other HR-HPV positive cases (12.95%). During the 4-year period, 83 cases of CIN2 or higher were diagnosed. The sensitivity and specificity of baseline HR-HPV positivity for CIN2 or higher were 89.16% (95% CI: 80.66%-94.19%) and 85.74% (95% CI: 84.36%-87.02%), respectively. The corresponding rates for HPV 16/18 positivity were 43.37% (95% CI: 33.24%-54.09%) and 97.67% (95% CI: 97.02%-98.18%). The 4-year cumulative absolute risk of CIN2 or higher was highest in the HPV 16/18 positive group (36.73%, 95% CI: 27.85%-46.62%), followed by other HR-HPV positive groups (10.70%, 95% CI: 7.87%-14.38%), and the HR-HPV negative group was the lowest (0.39%, 95% CI: 0.19%-0.76%). Conclusions:HR-HPV genotyping testing exhibits high sensitivity and specificity for detecting CIN2 or higher lesions in cervical cancer screening. It also provides a scientific basis for stratifying the individual risk of developing CIN2 or higher lesions to guide subsequent management. Therefore, the HR-HPV genotyping testing can be considered as an effective method for cervical cancer screening.
2.Evaluation of high-risk HPV genotyping detection in cervical cancer screening based on a prospective cohort study
Hong WANG ; Yin LIU ; Huifang XU ; Peipei CHEN ; Xingyuan SUN ; Mengjie LI ; Peiyao LI ; Kunyao LI ; Liyang ZHENG ; Shuzheng LIU ; Xibin SUN ; Youlin QIAO ; Shaokai ZHANG
Chinese Journal of Oncology 2025;47(5):435-442
Objective:To evaluate the clinical performance of high-risk human papillomavirus (HR-HPV) genotyping in cervical cancer screening.Methods:Between June and July 2017, a prospective cervical cancer screening cohort was established in Xiaye Town, Jiyuan City, Henan Province, China by recruiting 3 254 women aged 21 to 64 years. At baseline screening, cervical exfoliated cell specimens were collected for HR-HPV genotyping and liquid-based cytology testing. Follow-ups were conducted over a 3-year period, with cytology testing in the first and second years and both HR-HPV genotyping and cytology testing in the third year. Women meeting the referral criteria were referred for colposcopy, with cervical biopsy and histopathological diagnosis performed as necessary. The endpoint was defined as cervical intraepithelial neoplasia grade 2 (CIN2) or higher confirmed by histopathological diagnosis. The sensitivity and specificity for detecting CIN2 or higher lesions of HR-HPV genotyping were calculated, as well as the cumulative risk of developing CIN2 or higher lesions over the 4-year study period in women with different baseline HR-HPV genotyping results.Results:A total of 2 741 women were included in the statistical analysis. Baseline HR-HPV genotyping detected 453 HR-HPV positive cases (16.53%), including 98 HPV 16/18 positive cases (3.58%) and 355 other HR-HPV positive cases (12.95%). During the 4-year period, 83 cases of CIN2 or higher were diagnosed. The sensitivity and specificity of baseline HR-HPV positivity for CIN2 or higher were 89.16% (95% CI: 80.66%-94.19%) and 85.74% (95% CI: 84.36%-87.02%), respectively. The corresponding rates for HPV 16/18 positivity were 43.37% (95% CI: 33.24%-54.09%) and 97.67% (95% CI: 97.02%-98.18%). The 4-year cumulative absolute risk of CIN2 or higher was highest in the HPV 16/18 positive group (36.73%, 95% CI: 27.85%-46.62%), followed by other HR-HPV positive groups (10.70%, 95% CI: 7.87%-14.38%), and the HR-HPV negative group was the lowest (0.39%, 95% CI: 0.19%-0.76%). Conclusions:HR-HPV genotyping testing exhibits high sensitivity and specificity for detecting CIN2 or higher lesions in cervical cancer screening. It also provides a scientific basis for stratifying the individual risk of developing CIN2 or higher lesions to guide subsequent management. Therefore, the HR-HPV genotyping testing can be considered as an effective method for cervical cancer screening.
3.Effect of Myod1 on proliferation and apoptosis of oxygen-glucose-deprived SHSY5Y cells by regulating lncRNA SNHG15 and miR-24-3p
Fangchao JI ; Chenxin ZHANG ; Zhanjun REN ; Yunzhi PAN ; Qi LU ; Xingyuan SUN
Journal of Jilin University(Medicine Edition) 2024;50(4):989-999
Objective:To investigate the effect of myogenic differentiation protein 1(Myod1)on the proliferation inhibition and apoptosis of the SH-SY5Y cells induced by oxygen-glucose deprivation(OGD),and to elucidate its mechanism.Methods:Real-time quantitative fluorescence PCR(RT-qPCR)method was used to detect the mRNA levels of Myod1 and long non-coding RNA(lncRNA)small nucleolar RNA host gene 15(SNHG15)in peripheral blood of the subjects in normal group and the patients in ischemic cerebral infarction group as well as the normal cultured SH-SY5Y cells(control group)and the cells in OGD model(OGD group).After transfecting SH-SY5Y cells with si-Myod1,pcDNA3.0-Myod1,si-SNHG15,pcDNA3.0-SNHG15、si-NC,Vector,miR-NC,and miR-24-3p mimics,the cells were treated with OGD,and then the SH-SY5Y cells were divided into control group,OGD group,OGD+Vector group,OGD+Myod1 group,OGD+si-NC group,OGD+si-Myod1 group,OGD+si-SNHG15 group,OGD+si-SNHG15+Vector group,OGD+si-SNHG15+Myod1 group,OGD+miR-NC group,OGD+miR-mimics group,OGD+miR-mimics+Vector group,and OGD+miR-mimics+SNHG15 group.CCK-8 method was used to detect the cell activities in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining was used to detect the rates of EDU positive cells in various groups;the rates of TdT-mediated dUTP nick end labeling(TUNEL)positive cells in various groups were detected by TUNEL staining;Western blotting method was used to detect the expression levels of cleaved caspase-3,cleaved caspase-9,B-cell lymphoma 2(Bcl-2)and Bcl-2 associated X protein(Bax)proteins in the cells in various groups;the association between Myod1 and SNHG15 was evaluated by chromatin immunoprecipitate(CHIP);dual luciferase reporter gene experiment was used to evaluate the targeting relationships between Myod1 and SNHG15 as well as SNHG15 and miR-24-3p.Results:Compared with normal control group,the expression levels of Myod1 and SNHG15 mRNA in peripheral blood of the patients in ischemic cerebral infarction group were significantly increased(P<0.05).Compared with control group,the expression levels of Myod1 and SNHG15 mRNA in the SH-SY5Y cells in OGD group were significantly increased(P<0.05).Compared with OGD group,the cell activities and rates of EdU positive cells in OGD+Myod1 group at 48 and 72 h were decreased(P<0.01),and the rates of TUNEL positive cells were increased(P<0.05);the cell activities and rates of EdU positive cells in OGD+si-Myod1 group were increased(P<0.05),while the rates of TUNEL positive cells were decreased(P<0.01).Myod1 binded to the promoter sequence of SNHG15.SNHG15 could absorb miR-24-3p,and there were target relatronships between Myod1 and SNHG15 as well as SNHG15 and miR-24-3p.After SNHG15 knockdown,compared with OGD group,the cell activities and rates of EdU positive cells in OGD+si-SNHG15 group at 48 and 72 h were increased(P<0.01),and the rates of TUNEL positive cells were decreased(P<0.01),the expression levels of Bax,cleaved caspase-3 and cleaved caspase-9 proteins were decreased(P<0.01),and the expression levels of Bcl-2 protein were increased(P<0.01).Compared with OGD+si-SNHG15 group,the cell activities and rates of EdU positive cells in OGD+si-SNHG15+Myod1 group at 48 and 72 h were decreased(P<0.05),the rates of TUNEL positive cells were(P<0.05),the expression levels of Bax,cleaved caspase-3,and cleaved caspase-9 proteins were increased(P<0.05),and the expression levels of Bcl-2 were decreased(P<0.05).After over-expression of miR-24-3p and SNHG15,compared with OGD group,the cell activities and rates of EdU positive cells in OGD+miR-mimics group at 48 and 72 h were increased(P<0.01),the rates of TUNEL positive cells were significantly decreased(P<0.01),the protein expression levels of Bax,cleaved caspase-3 and cleaved caspase-9 were decreased(P<0.05),and the expression levels of Bcl-2 were increased(P<0.01).Compared with OGD+miR-mimics group,the cell activities and rates of EdU positive cells in OGD+miR-mimics+SNHG15 group at 48 and 72 h were decreased(P<0.05),and the rates of TUNEL positive cells were increased(P<0.05),the expression levels of Bax,cleaved caspase-3 and cleaved caspase-9 proteins were increased(P<0.05),and the expression levels of Bcl-2 protein were decreased(P<0.05).Conclusion:Myod1 can promote the proliferation inhibition and apoptosis of OGD-induced SH-SY5Y cells by binding to the SNHG15 promoter region and then absorbing miRNA-24.
4.KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.
Cancan ZHENG ; Xiaomei YU ; Taoyang XU ; Zhichao LIU ; Zhili JIANG ; Jiaojiao XU ; Jing YANG ; Guogeng ZHANG ; Yan HE ; Han YANG ; Xingyuan SHI ; Zhigang LI ; Jinbao LIU ; Wen Wen XU
Acta Pharmaceutica Sinica B 2023;13(10):4217-4233
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.
5.Study progression on mechanism of long non-coding RNAs regulating drug resistance in osteosarcoma
Xiaoping MA ; Junli CHANG ; Xingyuan SUN ; Yanping YANG
Journal of International Oncology 2023;50(1):51-54
Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.
6.Clinicopathological characteristics and outcomes of 122 patients with colorectal cancer metastasize to the ovary
Qun LI ; Yiqun LI ; Honggang ZHANG ; Chi YIHEBALI ; Xingyuan WANG ; Lin YANG ; Aiping ZHOU ; Yan SONG ; Yongkun SUN ; Jinwan WANG ; Lingying WU ; Jing HUANG
Chinese Journal of Oncology 2021;43(1):132-136
Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.
7.Clinicopathological characteristics and outcomes of 122 patients with colorectal cancer metastasize to the ovary
Qun LI ; Yiqun LI ; Honggang ZHANG ; Chi YIHEBALI ; Xingyuan WANG ; Lin YANG ; Aiping ZHOU ; Yan SONG ; Yongkun SUN ; Jinwan WANG ; Lingying WU ; Jing HUANG
Chinese Journal of Oncology 2021;43(1):132-136
Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.
8. Evaluation the triage performance of p16/Ki-67 dual staining for HR-HPV positive women
Manman JIA ; Dongmei ZHAO ; Zhen GUO ; Zeni WU ; Peipei CHEN ; Peipei GUO ; Xingyuan SUN ; Shaokai ZHANG
Chinese Journal of Preventive Medicine 2020;54(2):192-197
Objective:
This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining for triage high risk HPV (HR-HPV) infected women.
Method:
Target objects were women who infected HR-HPV and received colposcopy examination between April and December of 2016 at the Second Affiliated Hospital of Zhengzhou University. Gynecologists collected the cervical exfoliated cells from eligible women for p16/Ki-67 dual staining, LBC testing and HPV DNA testing. Histology diagnosis were used as gold standard. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) of p16/Ki-67 dual staining, LBC testing and HPV16/18 testing for triage of HR-HPV positive population were calculated and compared.
Results:
A total of 295 HR-HPV infected women were selected, and the mean age was (44.29±11.48) years old. Positive rates of p16/Ki-67 dual staining, HPV16/18 testing and LBC testing were 70.17% (207), 56.95% (168) and 85.76% (253), respectively. When CIN2+as the endpoint, among the three triage methods, sensitivity of p16/Ki-67 dual staining was 90.00% (95
9.Therapeutic effect of hyperbaric oxygen therapy on patients with esophageal cancer and its impact on quality of life
Qi SUN ; Xingyuan LI ; Wenzhi HUANG ; Lijuan LU
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(3):305-308
Objective:To investigate the efficacy of hyperbaric oxygen (HBO) therapy in the treatment of esophageal cancer and its impact on patients′ quality of life.Methods:A total of 98 patients with esophageal cancer admitted to the PLA Navy Anqing Hospital from February 2014 to February 2016 were enrolled and randomly divided into control group and observation group, with 49 patients in each group. The control group was treated with chemotherapy. The observation group was treated with HBO on the basis of the treatment of control group. The short-term efficacy and adverse reactions of the two groups were compared. The quality of life was assessed by the Quality of Life Questionnaire-Core 30 (QLQ-C30) of cancer patients. After 3 years of follow-up, the long-term efficacies of the two groups were compared.Results:The near-term total effective rate of the observation group (44.9%) was obviously higher than that of the control group (36.7%), with statistically significant difference ( χ2=4.037, P<0.05). After treatment, the total scores of physical function and quality of life of the patients in the observation group were significantly higher than those in the control group, with statistically significant difference ( P<0.05). After 4 courses of treatment, the incidence of adverse reaction of the observation group was significantly lower than that of the control group ( P<0.05). During the 3-year-long follow-up, the 1-year survival rate of the observation group was significantly higher than that of the control group (79.6% vs. 59.2%, χ2=5.027, P<0.05). The 2-year and 3-year survival rates of the observation group were higher than those of the control group, but there was no significant difference ( P>0.05). Conclusion:HBO-assisted chemotherapy has a good clinical effect on the patients with esophageal cancer and can improve the quality of life, which is of perceivable clinical significance for the treatment of esophageal cancer.
10.Therapeutic effect of hyperbaric oxygen therapy on patients with esophageal cancer and its impact on quality of life
Qi SUN ; Xingyuan LI ; Wenzhi HUANG ; Lijuan LU
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(3):305-308
Objective:To investigate the efficacy of hyperbaric oxygen (HBO) therapy in the treatment of esophageal cancer and its impact on patients′ quality of life.Methods:A total of 98 patients with esophageal cancer admitted to the PLA Navy Anqing Hospital from February 2014 to February 2016 were enrolled and randomly divided into control group and observation group, with 49 patients in each group. The control group was treated with chemotherapy. The observation group was treated with HBO on the basis of the treatment of control group. The short-term efficacy and adverse reactions of the two groups were compared. The quality of life was assessed by the Quality of Life Questionnaire-Core 30 (QLQ-C30) of cancer patients. After 3 years of follow-up, the long-term efficacies of the two groups were compared.Results:The near-term total effective rate of the observation group (44.9%) was obviously higher than that of the control group (36.7%), with statistically significant difference ( χ2=4.037, P<0.05). After treatment, the total scores of physical function and quality of life of the patients in the observation group were significantly higher than those in the control group, with statistically significant difference ( P<0.05). After 4 courses of treatment, the incidence of adverse reaction of the observation group was significantly lower than that of the control group ( P<0.05). During the 3-year-long follow-up, the 1-year survival rate of the observation group was significantly higher than that of the control group (79.6% vs. 59.2%, χ2=5.027, P<0.05). The 2-year and 3-year survival rates of the observation group were higher than those of the control group, but there was no significant difference ( P>0.05). Conclusion:HBO-assisted chemotherapy has a good clinical effect on the patients with esophageal cancer and can improve the quality of life, which is of perceivable clinical significance for the treatment of esophageal cancer.

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