Analysis of the disease burden trend of malignant tumors of the female reproductive system in China from 2006 to 2020.

BACKGROUND: Malignant tumors of reproductive system seriously threaten women's life and health. We analyzed the changes in mortality and disease burden of cervical cancer, uterine cancer and ovarian cancer in China from 2006 to 2020 to provide a basis for formulating scientific prevention and control measures. METHODS: Annual death data for cervical cancer, uterine cancer and ovarian cancer were collected from the Chinese Cause of Death Surveillance. The crude mortality rate (CMR), age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were applied to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were used to assess disease burden. RESULTS: From 2006 to 2020, there was no significant change in the total ASMR and standardized YLL rates of malignant tumors of the reproductive system, leading to an average LLE of 0.18 years. The YLL rate was the highest in the 55-59 age group. The mortality rate and disease burden of the three types of cancer have changed from uterine cancer higher than cervical cancer and ovarian cancer in 2006 to cervical cancer higher than ovarian cancer and uterine cancer in 2020. The ASMR and standardized YLL rate of uterine cancer showed a downward trend, and AAPC was - 5.21% (- 9.31% ~ - 0.91%) and - 6.07% (- 9.45% ~ - 2.58%), respectively. The mortality rates of cervical cancer and ovarian cancer remain high. CONCLUSION: The mortality and disease burden of malignant tumors of the female reproductive system in China are still at a high level. It is necessary to improve screening and prevention strategies as soon as possible, improve the techniques of diagnosis and treatment, and take adequate measures to protect women's life and health.

Malignant tumors of the female reproductive system are the leading causes of women's mortality worldwide, mainly including cervical cancer, uterine cancer and ovarian cancer. Numerous studies have reported mortality changes in the three primary reproductive system cancers among different countries, with inconsistent temporal trends. In 2020, almost 17.51% of malignant tumors of the female reproductive system deaths occurred in China because of the large population base and severe aging. However, there are limited studies on the disease burden of malignant tumors of the female reproductive system in China. This study analyzed the mortality, YLL and LLE of cervical cancer, uterine cancer and ovarian cancer using the National Death Cause Surveillance Dataset from 2006 to 2020. The findings revealed that mortality and disease burden of malignant tumors of the reproductive system showed no significant change. The mortality and disease burden of uterine cancer decreased significantly, but that of cervical cancer and ovarian cancer remain high. Cervical cancer has a higher mortality and disease burden than uterine cancer and ovarian cancer, making it the most severe malignant tumor of the female reproductive system. Screening and HPV vaccination will reduce the mortality and disease burden of cervical cancer in China, but this effect will take many years to manifest. Screening and prevention strategies for high-risk groups of uterine cancer and ovarian cancer should be established as soon as possible. In summary, the management and monitoring of malignant tumors of the female reproductive system should be strengthened.

BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer.

Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC). B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3), a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is mediated by its downstream target gene, STAT3.

Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis.

Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation.