Investigator

Lei Li

Professor · Peking Union Medical College Hospital, Obstetrics and Gynecology

LLLei Li
Papers(12)
The prognosis of recu…The clinicopathologic…Role of the novel opt…Triage performance of…Intravenous leiomyoma…Cytologic …Successful management…Hsa-miR-105-1 Regulat…Minimally invasive ve…Efficacy of different…DNA methylation for c…Genomic alterations c…
Collaborators(10)
Huanwen WuMing WuHaiqi SuXiaojing ChenShuiqing MaXianjie TanXiaopei ChaoXiao ShangXinxin KouXitong Jin
Institutions(4)
Peking Union Medical …Nantong UniversityLuoyang Central Hospi…Beijing Origin-Poly B…

Papers

The prognosis of recurrent low-grade endometrial stromal sarcoma: a retrospective cohort study

AbstractBackgroundThe prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS.MethodsPatients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities.ResultsFifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2–30.8) and 75.0% (68.0–82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5–13.1, 1.3–7.3, and 0.1–0.7; andp = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1–1.0 and 0.1–1.0,p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse.ConclusionFor patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study

AbstractLittle is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

Role of the novel optoelectronic imaging tracing system in cervical cancer screening: preliminary outcomes of a multi-center study

This study aimed to evaluate the diagnostic performance of the novel Optoelectronic Imaging Tracing System as a triage or adjunct tool for women with high-risk human papillomavirus (hrHPV) infections. Between June 2024 and August 2024, 581 women aged 18 to 65 years undergoing colposcopy were enrolled. The performance of hrHPV testing, cytology, the Optoelectronic Imaging Tracing System, and their combinations in detecting cervical intra-epithelial neoplasia grade 2 or worse and cervical intra-epithelial neoplasia grade 3 or worse was compared by assessing sensitivity, specificity, odds ratios, and area under the receiver operating characteristic curve (AUC). The Optoelectronic Imaging Tracing System demonstrated high sensitivity for detecting cervical intra-epithelial neoplasia grade 2 or higher (96.0%, 95% CI 93.5% to 98.6%) and grade 3 or higher (95.5%, 91.1% to 99.8%), and showed the highest odds ratios for detecting grade 2 or higher (26.0, 13.6 to 56.3) and grade 3 or higher (10.2, 3.72 to 43.3), respectively. In contrast, HPV16/18 genotyping had the highest specificity (65.9% [61.0% to 70.8%] and 63.7% [59.4% to 67.9%], respectively). In detecting cervical intra-epithelial neoplasia grade 2 or higher, the best AUC was achieved by the Optoelectronic Imaging Tracing System alone (0.742, 0.713 to 0.771), whereas the combination of the Optoelectronic Imaging Tracing System and HPV16/18 genotyping had the best AUC in detecting cervical intra-epithelial neoplasia grade 3 or higher (0.699, 0.645 to 0.753). No complaints or adverse events were reported by the participants. This exploratory study demonstrated the potential of the Optoelectronic Imaging Tracing System as a safe and effective triage or adjunct tool for detecting high-grade cervical lesions in women with hrHPV infections.

Triage performance of DNA methylation for women with high-risk human papillomavirus infection

Abstract Objective DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3). Methods The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. Results For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. Conclusions PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

Intravenous leiomyomatosis with cardiac involvement: clinicopathological and molecular insights including fumarate hydratase deficiency

Aims The objective of this study was to explore the clinical diagnostic indicators and treatment approaches for intravenous leiomyomatosis (IVL), particularly when it extends into the inferior vena cava and the right heart system. Methods Nine patients with IVL admitted to our hospital were enrolled in this study. The ultrasonographic, CT, MRI, pathological findings and surgical details of these patients were comprehensively analysed. All patients underwent surgical procedures. Postoperative pathological examination confirmed the presence of IVL, along with intramural leiomyoma of the uterus. Results Immunohistochemical results demonstrated that smooth muscle actin, smooth muscle myosin heavy chain, Desmin, Caldesmon, oestrogen receptor and progesterone receptor were highly positive. The Ki-67 index of most specimens was <3%, except for case 4. In case 4, which invaded the right atrium, the Ki-67 index ranged from 2% to 5%. Through molecular testing, this case with extension to the right atrium and inferior vena cava was identified as intraventricular smooth muscle neoplasia with fumarate hydratase deficiency. No copy number variation mutations were detected in all cases. Conclusions Although IVL is a rare histologically benign tumour, it exhibits the capacity to infiltrate cardiac chambers and pulmonary vasculature. Therefore, early diagnosis via imaging techniques, precise assessment of the extent of intravenous leiomyoma involvement, complete lesion resection and perioperative administration of anti-oestrogen medications are pivotal for enhancing patient prognosis. Additionally, for cases with atypical nuclei or high Ki-67 levels, multidisciplinary collaboration is required to personalised treatment.

Cytologic DNA methylation for managing minimally abnormal cervical cancer screening results

Abstract Objectives To explore the role of a DNA methylation assay for managing minimally abnormal cervical cancer screening results in a prospective cohort undergoing opportunistic cervical cancer screening. Methods In the cohort of the METHY2 and METHY3 screening studies of women undergoing opportunistic cervical cancer screening, cervical cytology samples were sent for high‐risk human papillomavirus (hrHPV) DNA assays, cytologic pathology and methylation assays of PAX1 / JAM3 (CISCER). This study evaluated the discriminative power of CISCER in managing women with minimally abnormal cervical cancer screening results for CIN3+. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. Results A total of 1857 women with minimally abnormal cervical cancer findings had cervical histologic outcomes and were included in the analysis. In women with a minimally abnormal cervical cancer result, the sensitivity and specificity of CISCER was 74.9% (95% confidence interval [CI], 68.3%–81.4%) and 89.1% (95% CI 87.6%–90.6%) for detecting CIN3+. CISCER analysis discriminated well for minimally abnormal cervical cancer results, yielding a CIN3+ risk of 40.5% (95% CI 34.9%–46.2%) after a positive result and a CIN3+ risk of 2.7% (95% CI 2.0%–3.6%) after a negative result. Conclusions In women with a minimally abnormal cervical cancer screening result, the CISCER provides excellent detection of CIN3+. The use of CISCER in women with a minimally abnormal cervical cancer screening result can lead to a substantial reduction in the number of direct colposcopy referrals.

Hsa-miR-105-1 Regulates Cisplatin-Resistance in Ovarian Carcinoma Cells by Targeting ANXA9

Purpose. Cisplatin is one of the most effective drugs for treating ovarian carcinoma (OC), which is among the most lethal types of carcinoma. However, the chemoresistance to cisplatin that develops over time leads to a poor clinical outcome for many OC patients. Therefore, it is necessary to clearly understand the molecular mechanisms of chemoresistance. In this study, we examined how Hsa-miR-105-1 functions in cisplatin-resistant OC cells. Methods. The levels of Hsa-miR-105-1 expression in cisplatin-sensitive and resistant OC cell lines were detected by qRT-PCR. The target gene of Hsa-miR-105-1 was predicted by using the TargetScan and Starbase databases and verified by the double luciferase reporter gene assay. The target gene of Hsa-miR-105-1 was identified as ANXA9, and ANXA9 expression was evaluated by qRT-PCR, western blotting, and immunofluorescence. To validate the function of Hsa-miR-105-1 in OC cells, we silenced or overexpressed Hsa-miR-105-1 in cisplatin-sensitive or resistant OC cell lines, respectively. Furthermore, the expression levels of several apoptosis-related proteins, including P53, P21, E2F1, Bcl-2, Bax, and caspase-3, were examined by western blot analysis. Results. The levels of Hsa-miR-105-1 expression were abnormally downregulated in cisplatin-resistant OC cells, while ANXA9 expression was significantly upregulated in those cells. Treatment with an Hsa-miR-105-1 inhibitor promoted the expression of ANXA9 mRNA and protein, enhanced the resistance to cisplatin, and attenuated the cell apoptosis induced by cisplatin in cisplatin-sensitive OC cells. Moreover, treatment with Hsa-miR-105-1 mimics inhibited ANXA9 expression, which further increased the levels of P53, P21, and Bax expression and decreased the levels of E2F1 and Bcl-2 expression, finally resulting in an increased sensitivity to cisplatin in cisplatin-resistant OC cells. Conclusion. We found that a downregulation of Hsa-miR-105-1 expression enhanced cisplatin-resistance, while an upregulation of Hsa-miR-105-1 restored the sensitivity of OC cells to cisplatin. The Hsa-miR-105-1/ANXA9 axis plays an important role in the cisplatin-resistance of OC cells.

Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China

Abstract Background There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China. Methods This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up. Discussion The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility. Trial registration ClinicalTrials.gov NCT03739944. Registered on November 14, 2018

Efficacy of different surgical approaches on survival outcomes in patients with early-stage cervical cancer: protocol for a multicentre longitudinal study in China

IntroductionRecent studies have revealed that the oncological survival outcomes of minimally invasive radical hysterectomy (MIRH) are inferior to those of abdominal radical hysterectomy (ARH) in early-stage cervical cancer, but the potential reasons are unclear.Methods and analysisEach expert from 28 study centres participating in a previously reported randomised controlled trial (NCT03739944) will provide successive eligible records of at least 100 patients who accepted radical hysterectomy for early-stage cervical cancer between 1 January 2009 and 31 December 2015. Inclusion criteria consist of a definite pathological evaluation of stages IA1 (with positive lymphovascular space invasion), IA2 and IB1 according to the International Federation of Gynecology and Obstetrics 2009 staging system and a histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. The primary endpoint is 5-year disease-free survival between the MIRH and ARH groups. The secondary endpoints include the MIRH learning curves of participating surgeons, 5-year overall survival between the MIRH and ARH groups, survival outcomes according to surgical chronology, surgical outcomes and sites of recurrence and potential risk factors that affect survival outcomes. A subgroup analysis in patients with tumour diameter less than 2 cm will follow the similar flow diagram.Ethics and disseminationThis study has been approved by the Institutional Review Board of Peking Union Medical College Hospital (registration no. JS-1711), and is also filed on record by all other 27 centres. The results will be disseminated through community events and peer-reviewed journals.Trial registration numberNCT03738969

DNA methylation for cervical cancer screening: a training set in China

Abstract Background Despite rapid improvements in DNA methylation tools for cervical cancer screening, few robust, exploratory studies have been performed using the combination of two host genes, EPB41L3 and JAM3, newly developed assays. Methods A review of abnormal liquid-based cytology and/or high-risk human papillomavirus (hrHPV) data from outpatient clinics in the study center from March 2018 to March 2019 was performed. Eligible patients with definitive histological pathology results were included, and their residual cytology samples were assessed for EPB41L3 and JAM3 methylation. The diagnostic accuracies of various screening strategies for definitive pathology and for cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+) were compared. Results In total, 306 patients were successfully tested; 301 cases with cervical histological pathology were included in the final analysis, including 118 (39.2%) and 183 (60.8%) cases of inflammation/CIN1 and CIN2+, respectively. Regarding CIN2+ detection, methylation status and hrHPV plus methylation had similar positive predictive values (0.930 and 0.954, respectively, p = 0.395). Additionally, hrHPV, methylation, and hrHPV plus methylation had similar negative predictive values (0.612, 0.679, and 0.655, p = 0.677) that were significantly higher than that of cytology alone (0.250, p values 0.012, 0.001, and 0.001, respectively). For 49 cases with negative hrHPV results, positive methylation alone was able to differentiate CIN2+ from inflammation/CIN1. Conclusions Methylation of both EPB41L3 and JAM3 is an accurate and feasible screening method for CIN2+.

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Effects of long-acting versus short-acting granulocyte colony stimulating factor after radiotherapy in gynecologic malignancies: a prospective observational cohort study

Little is known about the role of the protective effects of granulocyte colony-stimulating factor (G-CSF) in patients after radiotherapy. The aim of the present study was to explore the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia (FN) and myelosuppression in chemotherapy patients with gynecologic malignancies after pelvic radiotherapy. Patients voluntarily participated in a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF) after they were educated about G-CSF utilization. The incidences of FN and myelosuppression, as well as adverse events, were compared between the two groups. A regression model was used to determine the risk factors for FN and myelosuppression. From January 6, 2019, to August 22, 2019, 61 patients were included in the final analysis, with 286 chemotherapy cycles. There were 14 (23.0%) and 57 (77.0%) patients in the study and control groups, respectively. The study group had significantly fewer complete blood count tests, fewer outpatient clinic visits, fewer short-acting G-CSF doses, and lower incidences of FN and myelosuppression per chemotherapy cycle. According to the binary regression model, the use of long-acting G-CSF was the only factor associated with a decreased incidence of myelosuppression but not FN. The major adverse event related to G-CSF was mild bone pain. In conclusion, long-acting G-CSF may effectively reduce the incidence of FN and myelosuppression with mild adverse effects during chemotherapy after radiotherapy.Trial registrationRegistered at https://www.clinicaltrials.gov/  on January 4, 2019 (NCT03793205).

Clinical Trials (2)

17Works
16Papers
22Collaborators
2Trials

Positions

Professor

Peking Union Medical College Hospital · Obstetrics and Gynecology

Education

2005

MD

Peking Union Medical College · Clinical Medicine

2000

MD

Peking University · College of Life Sciences