Jinghe Lang

FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway

Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. We also found the WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention. This study provides insight into the relationship between obesity and the pathogenesis of endometrial cancer while highlighting future areas of research.

Comparison between laparoscopic and abdominal radical hysterectomy for stage IB1 and tumor size <2 cm cervical cancer with visible or invisible tumors: a multicentre retrospective study

To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type. LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58-1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65-2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors. International Clinical Trials Registry Platform Identifier: CHiCTR180017778.

Comparison between robot-assisted radical hysterectomy and abdominal radical hysterectomy for cervical cancer: A multicentre retrospective study

To compare 3-year overall survival (OS) and disease-free survival (DFS) rates of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer. We retrospectively compared the oncological outcomes of 10,314 cervical cancer patients who received RRH (n = 1048) or ARH (n = 9266) and whose stages were IA1 with lymphovascular space invasion (LVSI)-IIA2. Kaplan-Meier survival analysis and log-rank tests were used to compare the 3-year OS and DFS rates between the RRH and ARH groups. Cox proportional hazards model and propensity score matching was used to estimate the surgical approach-specific survival. RRH and ARH showed similar 3-year OS and DFS rates (93.5% vs. 94.1%, p = 0.486; 90.0% vs. 90.4%, p = 0.302). RRH was not associated with a lower 3-year OS rate by the multivariable analysis (HR 1.23, 95% CI 0.89-1.70, p = 0.206), but it was associated with a lower 3-year DFS rate (HR 1.20, 95% CI 1.09-1.52, p = 0.035). After propensity score matching, patients who underwent RRH had decreased 3-year OS and DFS rates compared to those who underwent ARH (94.4% vs. 97.8%, p = 0.002; 91.1% vs. 95.4%, p = 0.001), and RRH was associated with lower 3-year OS and DFS rates. Among patients with stage IB1 and tumor size <2 cm, RRH was not associated with decreased 3-year OS and DFS rates (HR1.688, 95% CI 0.423-6.734, p = 0.458; HR1.267, 95%CI 0.518-3.098, p = 0.604). Overall, RRH was associated with worse 3-year oncological outcomes than ARH in patients with FIGO stage IA1 with LVSI- IIA2 cervical cancer. However, RRH showed similar 3-year oncological outcomes with ARH among those with stage IB1 and tumor size <2 cm.

Fragmentomics features of ovarian cancer

AbstractOvarian cancer (OC) is a major cause of cancer mortality in women worldwide. Due to the occult onset of OC, its nonspecific clinical symptoms in the early phase, and a lack of effective early diagnostic tools, most OC patients are diagnosed at an advanced stage. In this study, shallow whole‐genome sequencing was utilized to characterize fragmentomics features of circulating tumor DNA (ctDNA) in OC patients. By applying a machine learning model, multiclass fragmentomics data achieved a mean area under the curve (AUC) of 0.97 (95% CI 0.962–0.976) for diagnosing OC. OC scores derived from this model strongly correlated with the disease stage. Further comparative analysis of OC scores illustrated that the fragmentomics‐based technology provided additional clinical benefits over the traditional serum biomarkers cancer antigen 125 (CA125) and the Risk of Ovarian Malignancy Algorithm (ROMA) index. In conclusion, fragmentomics features in ctDNA are potential biomarkers for the accurate diagnosis of OC.