Quantitative proteomics analysis in small cell carcinoma of cervix reveals novel therapeutic targets.

BACKGROUND: As a rare pathologic subtype, small cell carcinoma of the cervix (SCCC) is characterized by extensive aggressiveness and resistance to current therapies. To date, our knowledge of SCCC origin and progression is limited and sometimes even controversial. Herein, we explored the whole-protein expression profiles in a panel of SCCC cases, aiming to provide more evidence for the precise diagnosis and targeting therapy. METHODS: Eighteen SCCC samples and six matched normal cervix tissues were collected from January 2013 to December 2017. Data independent acquisition mass spectrometry (DIA) was performed to discriminate the different proteins (DEPs) associated with SCCC. The expression of CDN2A and SYP in corresponding SCCC tissues was verified using immunohistochemistry. GO and KEGG enrichment analyses were used to identify the key DEPs related to SCCC development and tumor recurrence. RESULTS: As a result, 1311 DEPs were identified in SCCC tissues (780 up-regulated and 531 down-regulated). In up-regulated DEPs, both GO analysis and KEGG analysis showed the most enriched were related to DNA replication (including nuclear DNA replication, DNA-dependent DNA replication, and cell cycle DNA replication), indicating the prosperous proliferation in SCCC. As for the down-regulated DEPs, GO analysis showed that the most enriched functions were associated with extracellular matrix collagen-containing extracellular matrix. KEGG analysis revealed that the DEPs were enriched in Complement and coagulation cascades, proteoglycans in cancer, and focal adhesion-related pathways. Down-regulation of these proteins could enhance the mobility of cancer cells and establish a favorable microenvironment for tumor metastasis, which might be accounted for the frequent local and distant metastasis in SCCC. Surprisingly, the blood vessels and circulatory system exhibit a down-regulation in SCCC, which might be partly responsible for its resistance to anti-angiogenic regimens. In the stratification analysis of early-stage tumors, a group of enzymes involved in the cancer metabolism was discriminated in these recurrence cases. CONCLUSIONS: Using quantitative proteomics analysis, we first reported the whole-protein expression profiles in SCCC. Significant alterations were found in proteins associated with the enhancement of DNA replication and cellular motility. Besides the association with mitosis, a unique metabolic feature was detected in cases with tumor recurrence. These findings provided novel targets for disease surveillance and treatments, which warranted further validation in the future.

LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway.

Cervical cancer (CC) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long-term papillomavirus infection. Recent studies have shifted their focus and research attention to the relationship between long non-coding RNAs (lncRNAs) and CC therapeutic. Thus, the aim of the current study was to investigate the underlying mechanism of lncRNA LINC01305 on the cell invasion, migration and epithelial-mesenchymal transition (EMT) of CC cells via modulation of the PI3K/Akt signalling pathway by targeting tenascin-X B (TNXB). The expressions of LINC01305, TNXB, MMP2, MMP9, E-cadherin, vimentin, PI3K, Akt, p-PI3K, p-Akt and TNXB were detected in this study. After which, the cell invasion and migration abilities of the CC cells were determined respectively. Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that TNXB is the target gene of lncRNA LINC01305. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods revealed that the expressions of MMP2, MMP9, vimentin, PI3K, Akt, p-PI3K and p-Akt were decreased following the down-regulation of LncRNA LINC01305 or overexpression of TNXB. LncRNA LINC01305 silencing or TNXB overexpression was noted to decrease the migration and invasion of SiHa cells. Taken together, the key findings of the current study present evidence suggesting that lncRNA LINC01305 silencing suppresses EMT, invasion and migration via repressing the PI3K/Akt signalling pathway by means of targeting TNXB in CC cells, which ultimately provides novel insight and identification of potential therapeutic targets for CC.

The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer.

Objectives Our goal was to investigate the effects of rucaparib on the proliferation of cervical cancer cells and sensitivity to radiotherapy. Methods We used the human cervical cancer cell lines Hela and Siha and evaluated their viability and activity using various methods. Cellular proliferation was assessed by CCK-8 and clonogenic assays after treatment with rucaparib. Cell cycle analysis was performed using propidium iodide staining. Western immunoblotting analysis was used to detect the expression of cyclin D1 and CDK4. Immunofluorescence staining assay was performed to detect the expression of the DNA injury marker ×¥-H2AX after treatment with rucaparib and radiotherapy. Animal experiments were also performed to evaluate tumor size after treatment with rucaparib. Immunohistochemistry was performed to analyze the expression of Ki-67. Results Rucaparib suppressed proliferation, induced G2/M phase arrest, and reduced the expression of cyclin D1 and CDK4 in cervical cancer cells. When rucaparib was combined with radiotherapy in cervical cancer cells, clone formation decreased significantly and G2/M phase arrest was accentuated. The expression of the DNA-damage marker ×¥-H2AX was increased significantly, and rucaparib suppressed tumor growth in vivo. Conclusions Rucaparib exerts significant anti-proliferative effects and can serve as an effective radiosensitizer in cervical cancer, suggesting its candidacy in cervical cancer treatment and worthiness for further investigation.

The overexpression of PXN promotes tumor progression and leads to radioresistance in cervical cancer.

AIM: We aim to investigate the functions of PXN in cervical cancer. MATERIALS & METHODS: PXN protein was investigated by immunohistochemistry in a panel of cervical cancer. A series of in vitro and in vivo assays were used to explore the efficacy of PXN. RESULTS: PXN was significantly upregulated in cervical cancer, which associated with tumor stage, poor differentiation, lymphovascular space invasion and lymphatic metastasis. Knockdown of PXN notably impaired cellular growth and colony formation by suppressing Bcl-2 and inducing marked apoptosis. Moreover, PXN led to resistance to radiation, and downregulation of PXN resensitized C33A cells to radiation. CONCLUSION: PXN was frequently upregulated and acted as an oncogene via regulating Bcl-2 in cervical cancer, which supports PXN as a potent therapeutic target.

HOTAIR: a key regulator in gynecologic cancers.

Long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of human cancers. HOX transcript antisense RNA (HOTAIR) is an lncRNA localized to the mammalian HOXC gene cluster; it can interact with polycomb repressive complex 2 and the lysine-specific histone demethylase/CoREST/REST complex, and it manipulates the expression of various genes. HOTAIR promotes tumor invasion and metastasis by silencing tumor suppressors, and activating oncogenes and signaling pathways. HOTAIR is deregulated in many human cancers; despite its critical roles in health and disease, the underlying mechanisms governing HOTAIR function are unknown. In this review, we summarize the recent findings on the roles of HOTAIR in gynecologic cancers.

HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and poor prognosis in a Chinese population.

AIM: The aim of this study was to determine if HOTAIR rs920778 polymorphism is associated with ovarian cancer susceptibility and prognosis. MATERIALS & METHODS: The data were obtained from two independent groups including 329 ovarian cancer patients and 680 cancer-free, age-matched women. Blood samples were collected and genomic DNA was extracted for genotyping. RESULTS: TT genotype and T allele of HOTAIR rs920778 were significantly associated with a decreased ovarian cancer risk (p = 0.0004 and p < 0.0001, respectively), which associated with advanced tumor stage, lymph node metastasis and poor prognosis. Moreover, TT and TC carriers obtained a much shorter survival (p = 0.026). CONCLUSION: These findings propose that HOTAIR rs920778 polymorphism influences ovarian cancer susceptibility and prognosis, and further studies are warranted in other populations.

Deregulated miRNAs in human cervical cancer: functional importance and potential clinical use.

Cervical cancer (CC) is one of the most common malignancies affecting women worldwide. While the morbidity and mortality associated with CC are decreasing in western countries, they both remain high in developing countries. Unfortunately, many issues about molecular mechanisms of CC are not clear yet. miRNAs are a group of small noncoding RNAs that could post-transcriptionally modulate the expression of specific genes and participate in the initiation and progression of multiple diseases including CC. In the last decade, mounting evidences suggest an association between miRNAs and human papillomavirus infection, as well as variations in biologic behavior, treatment response and prognosis in CC. Herein, we highlight the latest findings in this area and the potential applications.

Overexpression of long non-coding RNA HOTAIR leads to chemoresistance by activating the Wnt/ß-catenin pathway in human ovarian cancer.

Overexpression of HOTAIR (HOX antisense intergenic RNA) is significantly correlated with tumor progression and poor prognosis in human ovarian cancer. However, the underlying mechanisms are largely unknown. In the present study, we investigated the roles of HOTAIR in the initiation and chemoresistance of ovarian cancer. As our data show, HOTAIR overexpression promoted cell cycle progression (and thus cell proliferation) by activating the wnt/ß-catenin signaling pathway. Likewise, knockdown of HOTAIR suppressed cell proliferation and arrested cell cycle at G1 phase via inhibition of wnt/ß-catenin signaling. Moreover, the results of primary culture demonstrated that elevated HOTAIR expression correlated positively with chemoresistance in ovarian cancer. In vitro and in vivo, HOTAIR induced cellular resistance to cisplatin by activating the wnt/ß-catenin pathway, which could be reversed by pre-treatment with the wnt/ß-catenin inhibitor, XAV939. In conclusion, HOTAIR promotes the initiation and chemoresistance of ovarian cancer by activating wnt/ß-catenin signaling, suggesting that HOTAIR might be a potent therapeutic target for ovarian cancer treatment.

A high level of circulating HOTAIR is associated with progression and poor prognosis of cervical cancer.

We recently found that HOTAIR (HOX antisense intergenic RNA) promotes development and induces radioresistance in cervical cancer. In the present study, we investigated the circulating HOTAIR expression and determined its relationships with the clinicopathological parameters in cervical cancer. The sera samples were obtained from 118 pathological diagnosed cervical cancer patients and 100 normal age-matched women. The expression of HOTAIR was measured by quantitative real time PCR. Patients' information were collected and analyzed by the SPSS 17.0 software. Compared with normal control, the expression of HOTAIR was significantly upregulated in the sera of cervical cancer patients (P < 0.0001). In addition, elevated HOTAIR was associated with advanced tumor stages (P < 0.0001), adenocarcinoma (P < 0.0001), lymphatic vascular space invasion (P = 0.0065), and lymphatic node metastasis (P = 0.0259). In addition, our follow-up data showed that high HOTAIR was notably correlated with tumor recurrence (P = 0.013) and short overall survival (P = 0.009). Circulating HOTAIR was commonly upregulated and a potent prognostic marker in cervical cancer.

Suppression of the epithelial-mesenchymal transition by SHARP1 is linked to the NOTCH1 signaling pathway in metastasis of endometrial cancer.

BACKGROUND: Mechanisms governing the metastasis of endometrial cancer (EC) are poorly defined. Recent data support a role for Enhancer-of-split and hairy-related protein 1 (SHARP1), a basic helix-loop-helix transcription repressor, in regulating invasiveness and angiogenesis of several human cancers. However, the role of SHARP1 in metastasis of EC remains unclear. METHODS: Human EC cell lines (Ishikawa and HEC-1B) were used. SHARP1 was upregulated by lentivirus transduction, while intracellular domain of NOTCH1 (ICN) were upregulated by transient transfection with plasmids. Effects of SHARP1 on cell migration and invasion were evaluated by wound healing assay and transwell invasion assay. Experimental metastasis assay were performed in nude mice. Effects of SHAPR1 on protein levels of target genes were detected by western blotting. Furthermore, the association between SHARP1 and the NOTCH1/EMT pathway was further verified in EC tissue specimens by immunohistochemical analysis. RESULTS: Overexpression of SHARP1 in EC cells inhibited cell migration, invasion, and metastasis. Exogenous SHARP1 overexpression affected the proteins levels of genes involved in EMT process and NOTCH1 signaling pathway. Upregulation of ICN in SHARP1-overexpressing Ishikawa cells induced cell migration and an EMT phenotype. Additionally, immunohistochemical analysis demonstrated that SHARP1 protein levels were lower in metastatic EC than in primary tumors, and statistical analysis revealed correlations between levels of SHARP1 and markers of EMT and NOTCH1 signaling pathway in human EC tissue specimen. CONCLUSIONS: This work supports a role for SHARP1 in suppressing EMT and metastasis in EC by attenuating NOTCH1 signaling. Therefore, SHARP1 may be a novel marker for lymphatic metastasis in EC patients.

Over-expression of platelet-derived growth factor-D promotes tumor growth and invasion in endometrial cancer.

The platelet-derived growth factor-D (PDGF-D) was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human endometrial cancer. Alterations of PDGF-D mRNA and protein were determined by real time PCR, western blot and immunohistochemical staining. Up-regulation of PDGF-D was achieved by stably transfecting the pcDNA3-PDGF-D plasmids into ECC-1 cells; and knockdown of PDGF-D was achieved by transient transfection with siRNA-PDGF-D into Ishikawa cells. The MTT assay, colony formation assay and Transwell assay were used to detect the effects of PDGF-D on cellular proliferation and invasion. The xenograft assay was used to investigate the functions of PDGF-D in vivo. Compared to normal endometrium, more than 50% cancer samples showed over-expression of PDGF-D (p < 0.001), and high level of PDGF-D was correlated with late stage (p = 0.003), deep myometrium invasion (p < 0.001) and lympha vascular space invasion (p = 0.006). In vitro, over-expressing PDGF-D in ECC-1 cells significantly accelerated tumor growth and promoted cellular invasion by increasing the level of MMP2 and MMP9; while silencing PDGF-D in Ishikawa cells impaired cell proliferation and inhibited the invasion, through suppressing the expression of MMP2 and MMP9. Moreover, we also demonstrated that over-expressed PDGF-D could induce EMT and knockdown of PDGF-D blocked the EMT transition. Consistently, in xenografts assay, PDGF-D over-expression significantly promoted tumor growth and tumor weights. We demonstrated that PDGF-D was commonly over-expressed in endometrial cancer, which was associated with late stage deep myometrium invasion and lympha vascular space invasion. Both in vitro and in vivo experiments showed PDGF-D could promote tumor growth and invasion through up-regulating MMP2/9 and inducing EMT. Thus, we propose targeting PDGF-D to be a potent strategy for endometrial cancer treatment.

Diagnostic efficacy of combining diffusion-weighted magnetic resonance imaging with serum Mucin 1, Mucin 13, and Mucin 16 in distinguishing borderline from malignant epithelial ovarian tumors.

AIMS: To enhance ovarian tumor diagnosis beyond conventional methods, this study explored combining diffusion-weighted magnetic resonance imaging (DWI-MRI) and serum biomarkers (Mucin 1 [MUC1], MUC13, and MUC16) for distinguishing borderline from malignant epithelial ovarian tumors. METHODS: A total of 126 patients, including 71 diagnosed with borderline (BEOTs) and 55 with malignant epithelial ovarian tumors (MEOTs), underwent preoperative DWI-MRI. Region of interest (ROI) was manually drawn along the solid component's boundary of the largest tumor, focusing on areas with potentially the lowest apparent diffusion coefficient (ADC). For entirely cystic tumors, a free-form ROI enclosed the maximum number of septa while targeting the lowest ADC. Serum biomarkers were determined using enzyme-linked immunosorbent assay. RESULTS: Basic morphological traits proved inadequate for malignancy diagnosis, warranting this investigation. BEOTs had an ADC mean of (1.670 ± 0.250) × 103 mm2 /s, while MEOTs had a lower ADC mean of (1.332 ± 0.481) × 103 mm2 /s, with a sensitivity of 63.6% and specificity of 90.1%. Median MUC1 (167.0 U/mL vs. 87.3 U/mL), MUC13 (12.44 ng/mL vs. 7.77 ng/mL), and MUC16 (180.6 U/mL vs. 36.1 U/mL) levels were higher in MEOTs patients. The biomarker performance was: MUC1, sensitivity 50.9%, specificity 100%; MUC13, sensitivity 56.4%, specificity 78.9%; MUC16, sensitivity 83.64%, specificity 100%. Combining serum biomarkers and ADC mean resulted in a sensitivity of 96.4% and specificity of 100%. CONCLUSION: The integration of DWI-MRI with serum biomarkers (MUC1, MUC13, and MUC16) achieves exceptional diagnostic accuracy, offering a powerful tool for the precise differentiation between borderline and malignant epithelial ovarian tumors.

EMX2 is downregulated in endometrial cancer and correlated with tumor progression.

EMX2 (the human homologue of Drosophila empty spiracles gene 2) is a candidate tumor suppressor. However, its roles in endometrial cancer are still unknown. In this study, we evaluated EMX2 expression in different subtypes of endometrial cancer and its relationships with clinicopathologic characteristics. By immunohistochemical staining, we investigated the level of EMX2 protein in 122 endometrial cancer and 25 normal endometrium tissues. Correlations between EMX2 expression and clinicopathologic features of patients were analyzed using a statistical software. Compared with the normal endometrium, the expression of EMX2 was significantly downregulated in endometrial cancer tissues (P< 0.001). Reduced EMX2 expression was correlated with the tumor stage (P = 0.023), grade (P = 0.016), and the depth of myometrial invasion (P = 0.04), but not with age, pathologic subtype, lymph node metastasis, lymph vascular space invasion, or ER/PR/p53 status. Downregulation of EMX2 was associated with tumor progression and may be a critical factor in the carcinogenesis and progression of endometrial cancer, which provided a novel therapeutic target and a potential marker for prognostic prediction.

Real-world Efficacy Data on Anti-Angiogenic Drugs in Recurrent Small Cell Cervical Carcinoma: A Retrospective Study.

OBJECTIVE: Small cell carcinoma of the cervix (SCCC) is rare but extremely aggressive and resistant to current therapies. We herein evaluate the efficacy of bevacizumab, apatinib, and anlotinib in recurrent/metastatic SCCC patients in a real-world setting. METHODS: Recurrent/metastatic SCCC patients were recruited between January 2013 and July 2020. Baseline characteristics were extracted from medical records, and patients were divided into an anti-angiogenic group and non-anti-angiogenic group. The efficacy of treatments was determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Kaplan-Meier analysis was performed for survival analysis. RESULTS: Sixteen patients received anti-angiogenic drugs after tumor recurrence/metastasis; of them, 10 cases received them as first-line treatment, 5 cases as second-line treatment, and 1 case as fourth-line treatment. Another 23 patients received traditional therapies, including surgery, chemotherapy, and radiotherapy. The use of anti-angiogenic drugs in first-line treatment significantly prolonged progression-free survival (PFS) compared to the controls, with a median PFS of 8 months (2-20 months) and 3 months (1-10 months), respectively (P = .025). This trend was also notable in patients who started anti-angiogenic treatment after the second-line recurrence/metastasis. However, there was no benefits for overall survival (OS) in either the 10 first-line cases or all 16 cases (P = .499 and .31, respectively). Both bevacizumab and small molecule drugs (apatinib and anlotinib) presented similar efficacy in SCCC patients. CONCLUSIONS: At present, this is the largest cohort study that provides real-world data, showing that anti-angiogenic regimens could significantly prolong PFS in recurrent/metastatic SCCC. Aside from bevacizumab, the novel oral small molecule drugs provide more choices with similar efficacy. These findings warrant further validation in well-designed future studies.

Low-coverage whole-genome sequencing for the effective diagnosis of early endometrial cancer: A pilot study.

Background: Endometrial carcinoma (EC) is a disease that predominantly affects peri- and post-menopausal women and its incidence has continued to rise over recent years. Since the gold standard for EC diagnosis-hysteroscopic biopsy-is invasive, expensive, and unsuitable for wide use, there is an urgent need for a non-invasive method that exhibits both high sensitivity and high specificity. We therefore investigated the efficacy of UterCAD (the uterine exfoliated cell chromosomal aneuploidy detector) using tampon-collected specimens for the early detection of EC. Methods: We prospectively recruited 51 patients with a history of abnormal bleeding and who planned to undergo hysteroscopic examination or hysterectomy between March 2020 and January 2021. Before executing an invasive procedure, a tampon was inserted into the patient's vagina for 6 h to collect exfoliated cells from the uterine cavity. Total DNA was extracted and low-coverage whole-genome sequencing was performed on an Illumina HiSeq X10, and we analyzed the differences in chromosomal status between women with EC and those bearing benign lesions using UterCAD. Results: Thirty EC patients-including 26 with endometrioid carcinoma (EEC) and four with uterine serous carcinoma (USC), as well as 14 benign cases-were enrolled in our final analysis. Copy-number variations (CNVs) were detected in tampon specimens collected from 26 EC patients (83.3%), including 21 with EEC (80.7%) and four with USC (100%). In the benign group, only one woman with focal atypical hyperplasia presented with a 10q chromosomal gain (P < 0.001). In the EC group, the most common CNVs were copy gains of 8q (N = 14), 2q (N = 4), and 10q (N = 3); and copy losses of 2q (N = 3) and 17p (N = 2). When we stratified by FIGO stage, the CNV rates in stages IA, IB, and II/III were 83.3% (15/18), 85.7% (6/7), and 80.0% (4/5), respectively. At the optimal cutoff (|Z| ≥ 2.3), UterCAD discriminated 83.3% of EC cases from benign cases, with a specificity of 92.9%. Conclusions: We initially reported that UterCAD could serve as a non-invasive method for the early detection of EC, especially in the rare and aggressive USC subtype. The use of UterCAD might thus avoid unnecessary invasive procedures and thereby reduce the treatment burden on patients.

Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway.

Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.

A novel prognostic model to predict OS and DFS of stage II/III gastric adenocarcinoma patients in China.

Background: The prognosis of advanced gastric adenocarcinoma (GAC) after radical gastrectomy varies greatly. We aimed to build and validate a novel individualized nomogram based on inflammation index and tumor markers for patients with stage II/III GAC. Methods: A total of 755 individuals with stage II/III GAC who had undergone radical gastrectomy at the First Affiliated Hospital of Zhengzhou University between 2012 and 2017 were included in this retrospective study. The patients were randomly divided into a training cohort (n â€‹= â€‹503) and a validation cohort (n â€‹= â€‹252). Univariate and multivariate analyses were used to determine independent prognostic factors of overall survival (OS) and disease-free survival (DFS). A nomogram was developed based on these independent factors. The concordance index (C-index) and calibration curves were used to evaluate the predictive accuracy of the nomogram. Results: Univariate and multivariate analyses demonstrated that older age, poor differentiation, advanced stage, elevated neutrophil-to-lymphocyte ratio (NLR), lower hemoglobin, and high carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were significantly associated with lower OS and DFS and were independent prognostic factors in stage II/III GAC. The nomogram developed based on these factors in the training cohort showed excellent calibration and discrimination (OS: C-index â€‹= â€‹0.739, 95% CI â€‹= â€‹0.706-0.772; DFS: C-index â€‹= â€‹0.735, 95% CI â€‹= â€‹0.702-0.769). In the internal validation cohort, the nomogram was also well-calibrated for the prediction of OS and DFS; it was superior to the 8th edition UICC/AJCC TNM staging system (for OS: C-index â€‹= â€‹0.746 vs. 0.679, respectively; for DFS: C-index â€‹= â€‹0.736 vs. 0.675, respectively; P â€‹< â€‹0.001). Conclusion: The nomogram model could reliably predict OS and DFS in stage II/III gastric cancer patients with radical gastrectomy. It may help physicians make better treatment decisions.

The functions and potential roles of extracellular vesicle noncoding RNAs in gynecological malignancies.

Extracellular vesicles (EVs) are small membranous vesicles secreted by multiple kinds of cells and are widely present in human body fluids. EVs containing various constituents can transfer functional molecules from donor cells to recipient cells, thereby mediating intercellular communication. Noncoding RNAs (ncRNAs) are a type of RNA transcript with limited protein-coding capacity, that have been confirmed to be enriched in EVs in recent years. EV ncRNAs have become a hot topic because of their crucial regulating effect in disease progression, especially in cancer development. In this review, we summarized the biological functions of EV ncRNAs in the occurrence and progression of gynecological malignancies. In addition, we reviewed their potential applications in the diagnosis and treatment of gynecological malignancies.

Assessment of plum rain's impact on power system emissions in Yangtze-Huaihe River basin of China.

As a typical climate that occurs in the Yangtze-Huaihe River basin of China with a size of 500,000 km2, plum rain can reduce the photovoltaic (PV) potential by lowering the surface irradiance (SI) in the affected region. Based on hourly meteorological data from 1980 to 2020, we find that plum rain can lower the SI in the affected region with a weekly peak drop of more than 20% at the most affected locations. This SI drop, coupled with a large number of deployed PV systems, can cause incremental CO2 emissions (ICEs) of local power systems by increasing the additional thermal power. Using a cost optimization model, we demonstrate that the ICEs in 2020 already reached 1.22 megatons and could range from 2.21 to 4.73 megatons, 3.47 to 7.19 megatons, and 2.97 to 7.43 megatons in 2030, 2040, and 2050, respectively, considering a change trend interval of a ±25% fluctuation in power generation and demand in the different years. To offset these ICEs, we compare four pathways integrated with promising technologies. This analysis reveals that the advanced deployment of complementary technologies can improve the PV utilization level to address climate impacts.