The Biosynthesis Pattern and Transcriptome Analysis of Sapindus saponaria Oil.

The Sapindus saponaria (soapberry) kernel is rich in oil that has antibacterial, anti-inflammatory, and antioxidant properties, promotes cell proliferation, cell migration, and stimulates skin wound-healing effects. S. saponaria oil has excellent lubricating properties and is a high-quality raw material for biodiesel and premium lubricants, showing great potential in industrial and medical applications. Metabolite and transcriptome analysis revealed patterns of oil accumulation and composition and differentially expressed genes (DEGs) during seed development. Morphological observations of soapberry fruits at different developmental stages were conducted, and the oil content and fatty acid composition of the kernels were determined. Transcriptome sequencing was performed on kernels at 70, 100, and 130 days after flowering (DAF). The oil content of soapberry kernels was lowest at 60 DAF (5%) and peaked at 130 DAF (31%). Following soapberry fruit-ripening, the primary fatty acids in the kernels were C18:1 (oleic acid) and C18:3 (linolenic acid), accounting for an average proportion of 62% and 18%, respectively. The average contents of unsaturated fatty acids and saturated fatty acids in the kernel were 86% and 14%, respectively. Through the dynamic changes in fatty acid composition and DEGs analysis of soapberry kernels, FATA, KCR1, ECR, FAD2 and FAD3 were identified as candidate genes contributing to a high proportion of C18:1 and C18:3, while DGAT3 emerged as a key candidate gene for TAG biosynthesis. The combined analysis of transcriptome and metabolism unveiled the molecular mechanism of oil accumulation, leading to the creation of a metabolic pathway pattern diagram for oil biosynthesis in S. saponaria kernels. The study of soapberry fruit development, kernel oil accumulation, and the molecular mechanism of oil biosynthesis holds great significance in increasing oil yield and improving oil quality.

Role of increased IGFBP2 in trophoblast cell proliferation and recurrent spontaneous abortion development: A pilot study.

Recurrent spontaneous abortion (RSA) is a serious condition that adversely affects women's health. Differentially expressed proteins (DEPs) in plasma of patients experiencing RSA is helpful to find new therapeutic targets and identified with mass spectrometry. In 57 DEPs, 21 were upregulated and 36 were downregulated in RSA. Gene ontology analyses indicated that identified DEPs were associated with cell proliferation, including significantly downregulated insulin-like growth factor binding protein 2 (IGFBP2). Immunohistochemical result using clinical decidual tissues also showed that IGFBP2 expression was significantly decreased in RSA trophoblasts. Cell proliferation assay indicated that IGFBP2 treatment increased the proliferation and mRNA expressions of PCNA and Ki67 in trophoblast cells. Transcriptome sequencing experiments and Kyoto Encyclopedia of Genes and Genomes analyses revealed that gene expression for components in PI3K-Akt pathway in trophoblasts was significantly upregulated following IGFBP2 treatment. To confirm bioinformatics findings, we did cell-based experiments and found that treatment of inhibitors for insulin-like growth factor (IGF)-1 receptor-PI3K-Akt pathway significantly reduced IGFBP2-induced trophoblast cell proliferation and mRNA expressions of PCNA and Ki67. Our findings suggest that IGFBP2 may increase trophoblast proliferation through the PI3K-Akt signaling pathway to affect pregnancy outcomes and that IGFBP2 may be a new target for future research and treatment of RSA.

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula.

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development. Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67. The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.

Extraperitonealization of the ileal conduit decreases the risk of parastomal hernia: A single-center, randomized clinical trial.

Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.

Immune characteristics analysis and construction of a four-gene prognostic signature for lung adenocarcinoma based on estrogen reactivity.

Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.

CXCL10 and CCL5 as feasible biomarkers for immunotherapy of homologous recombination deficient ovarian cancer.

This study aims to identify biomarkers of ovarian cancer, specifically those tumors exhibiting homologous recombination deficiency (HRD), to contribute to the optimization of immunotherapy. We screened the differentially expressed genes coding for CXCL10 and CCL5 by analyzing the transcriptome data of patient with different HRD scores in the ovarian cancer cohort of the TCGA database and validated our results using pathological tissue sections. The cellular origin of CXCL10 and CCL5 were identified using the single-cell sequencing data extracted from the GEO database combined with the tumor mutational burden (TMB) and single nucleotide polymorphism (SNP) data obtained from the TCGA database. We found that CXCL10 and CCL5 expression levels were correlated with HRD score. Analysis of single-cell sequencing results and tumor mutation data suggested that both CXCL10 and CCL5 present in the tumor microenvironment were primarily derived from immune cells. In addition, we found that samples with high expression of CXCL10 and CCL5 also had higher stromal cell and immune cell scores, indicating low tumor homogeny. Further analysis showed that CXCL10 and CCL5 expression was associated with immune checkpoint-related genes, and the efficacy of using these proteins as biomarkers was significantly higher than that of PD-1 in predicting the effect of anti-PD-1 immunotherapy. The expression of CXCL10 and CCL5 had statistically different effects on the survival of patients, based on multivariate Cox regression. In summary, the results demonstrate that in ovarian cancer, the expression of CXCL10 and CCL5 are correlated with HRD. When CXCL10 and CCL5 are secreted by immune cells, immune cell infiltration can be chemotactic and predict the effect of immunotherapy more efficiently than using PD-1 as a biomarker. Therefore, CXCL10 and CCL5 look to be promising novel biomarkers to guide immunotherapy in ovarian cancer.

PHB promotes bladder cancer cell epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway.

As a member of PHB (prohibitin1) family, PHB plays important roles in many cancers, but its property in bladder carcinoma aggressiveness is unknown. This research was to explore the function and potential mechanism of PHB in bladder carcinoma in vivo and in vitro. The invasive abilities of cancer cell were determined by transwell and wound-healing assays. The function of PHB was confirmed by gene knockdown and overexpression methods. Further in vivo confirmation was performed in a nude mouse model with lung metastasis. The relationship of PHB and ß-catenin was confirmed by immunoprecipitation and immunofluorescence staining assays. The protein expression of epithelial-mescenchymal transition (EMT) and Wnt/ß-catenin signaling pathway was tested by immunofluorescence staining and western blotting assay. The depletion of PHB prevented bladder cancer cell invasiveness and inhibited EMT. Contrarily，the abilities of bladder carcinoma cells migration and invasion in vitro as well as metastasis in vivo were enhanced when the PHB overexpressed unnormally. Importantly, the ß-catenin was identified to be bound by PHB and ß-catenin knockdown reduced the cancer cell migration, invasion and EMT in PHB overexpressing cells. In addition, PHB stabilized ß-catenin by inhibiting its ubiqutin-mediated degradation thus leading to increased Wnt/ß-catenin signaling. These observations indicate that PHB could promote bladder cancer aggressiveness by binding with ß-catenin to prevent the degradation of ß-catenin and the localized invasive bladder cancer patients with PHB overexpression should take more aggressive postsurgical adjuvant anticancer therapies.

Rare Pseudo-Chediak-Higashi Inclusions in Therapy-Related Acute Myeloid Leukemia with Myelodysplasia-Related Changes.

BACKGROUND: Defined as rare large azurophilic cytoplasmic inclusions, Pseudo-Chediak-Higashi granules mimic those in granulocytes cytoplasm of Chediak-Higashi syndrome. Rare cases of hematopoietic and lymphoid tissues tumors showed Pseudo-Chediak-Higashi inclusions in cytoplasm, some of which presented with unusual morphological characteristics. METHODS: Herein, we report the first case, in which rare pseudo-Chediak-Higashi inclusions were observed in therapy-related acute myeloid leukemia with myelodysplasia-related changes (t-AML-MRC). RESULTS: The rare pseudo-Chediak-Higashi inclusions may be positive for Sudan black, and some scholars think that these rare inclusions are a kind of dysgranulopoiesis. CONCLUSIONS: The case highlights the significance of an integrated diagnostic work-up, with an interesting effect for morphology.

Lymphocyte-to-monocyte ratio after primary surgery is an independent prognostic factor for patients with epithelial ovarian cancer: A propensity score matching analysis.

Background: The aim of this study was to elucidate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) after primary surgery in epithelial ovarian cancer (EOC) patients using a propensity score matching (PSM) analysis. Methods: We retrospectively reviewed consecutive EOC patients who underwent primary surgery between January 2008 and December 2019. Patients were divided into two groups according to the optimal cutoff value of preoperative LMR. PSM (1:1) was conducted to eliminate confounding factors. A Cox proportional hazards model and the Kaplan-Meier estimator were employed to investigate the potential prognostic factors. Results: A total of 368 EOC patients were included in this study. The optimal cutoff value of LMR was identified as 4.65. Low preoperative LMR was significantly correlated with low albumin, high CA125 level, more blood loss, a high likelihood of ascites, advanced FIGO stage, and poor differentiation (all p < 0.05). After matching, Kaplan-Meier curves showed that the group with LMR < 4.65 experienced significantly shorter OS (p = 0.015). Multivariate Cox analysis revealed that low LMR (HR = 1.49, p = 0.041), advanced FIGO stage (HR = 5.25, p < 0.001), and undefined residual disease (HR = 3.77, p = 0.002) were independent factors in predicting poor OS. A forest plot revealed that LMR had better prognostic value in younger EOC patients, patients with BMI ≥ 25 kg/m2 and albumin ≥ 35 g/L, CA125 ≥ 35 U/L, patients who had undergone optimal surgery, and those who had completed chemotherapy. Additionally, low-LMR patients who had undergone incomplete chemotherapy had a shorter median OS compared with those who completed chemotherapy treatment (48.5 vs. 105.9 months, p = 0.026). Conclusions: LMR could be used as an independent prognostic factor for EOC patients after primary surgery; a noticeable negative effect of LMR was observed among EOC patients with age < 65, good preoperative nutritional status, and more aggressive tumor biology, and among those who underwent optimal surgery. Completing adjuvant chemotherapy is essential to improve survival outcomes among EOC patients with LMR < 4.65 after surgery.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Autochthonous DOM had solar disinfection effect but nitrate counteracted with them.

Pathogens in natural water can pose great threat to public health and challenge water quality. In sunlit surface water, dissolved organic matters (DOMs) can inactivate pathogens due to their photochemical activity. However, the photoreactivity of autochthonous DOM derived from different source and their interaction with nitrate on photo-inactivation remained limited understood. In this study, the composition and photoreactivity of DOM extracted from Microcystis (ADOM), submerged aquatic plant (PDOM) and river water (RDOM) were studied. Results revealed that lignin and tannin-like polyphenols and polymeric aromatic compounds negatively correlated with quantum yield of 3DOM*, whilst lignin like molecules positively correlated with •OH generation. ADOM had highest photoinactivation efficiency of E. coli, followed by RDOM and PDOM. Both the photogenerated •OH and low energy 3DOM* could inactivate bacteria damaging cell membrane and causing increase of intracellular reactive species. PDOM with more phenolic or polyphenols compounds not only weaken its photoreactivity, also increase regrowth potential of bacteria after photodisinfection. The presence of nitrate counteracted with autochthonous DOMs on photogeneration of •OH and photodisinfection activity, as well as increased the reactivation rate of PDOM and ADOM, which might be attributed to the increase of survival bacteria and more bioavailable fractions provided in systems.

Pregnancy Outcomes after Uterus-sparing Operative Treatment for Adenomyosis: A Systematic Review and Meta-analysis.

OBJECTIVE: A meta-analysis was conducted to evaluate the overall pregnancy outcomes after uterus-sparing operative treatment in patients with adenomyosis (AD). DATA SOURCES: We searched PubMed, Web of Science, Cochrane Library, and Embase for literature from January 2000 to January 2022. METHODS OF STUDY SELECTION: We included all studies reporting reproductive outcomes of uterine-sparing surgery for patients with AD with fertility requirements. Surgical treatment was classified as complete excision or incomplete removal of AD and nonexcisional techniques for induction of necrosis in AD. The latter included physically removing the tissue where pathology is present or disrupting the blood flow to the affected area, involving high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, and uterine artery embolization. Two independent researchers performed study selection according to the screening criteria. TABULATION, INTEGRATION, AND RESULTS: A total of 13 studies with 1319 patients with AD were included in this study, comprising 795 women wishing fertility. Pooled estimates of pregnancy, miscarriage, and live-birth rates after excisional treatment for women attempting to conceive were 40% (95% confidence interval [CI], 29-52), 21% (95% CI, 16-27), and 70% (95% CI, 64-76), respectively, and corresponding rates after nonexcisional treatment were 51% (95% CI, 42-60), 22% (95% CI, 13-34), and 71% (95% CI, 57-83), respectively. The differences were not statistically significant. CONCLUSION: Excisional treatment could be a treatment consideration for patients with symptomatic AD and infertility for several years or repeated failure of assisted reproductive technology. Nonexcisional techniques may be considered probably for AD-related infertility.

Prognostic significance and immune correlates of FADD in penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) with a poor prognosis lacks reliable biomarkers for stratifying patients. Fas-associated death domain (FADD) could regulate cell proliferation and has shown promising diagnostic and prognostic significance in multiple cancers. However, researchers have not determined how FADD exerts its effect on PSCC. In this study, we set out to investigate the clinical features of FADD and the prognostic impact of PSCC. Additionally, we also assessed the role of affecting the immune environment in PSCC. Immunohistochemistry was carried out to evaluate the protein expression of FADD. The difference between FADDhigh and FADDlow was explored by RNA sequencing from available cases. The immune environment evaluation of CD4, CD8, and Foxp3 was performed by immunohistochemical. In this study, we found that FADD was overexpressed in 19.6 (39/199) patients, and the overexpression of FADD was associated with phimosis (p=0.007), N stage (p<0.001), clinical stage (p=0.001), and histologic grade (p=0.005). The overexpression of FADD was an independent prognostic factor for both PFS (HR 3.976, 95% CI 2.413-6.553, p<0.001) and OS (HR 4.134, 95% CI 2.358-7.247, p<0.001). In addition, overexpression of FADD was mainly linked to T cell activation and PD-L1 expression combined with PD-L1 checkpoint in cancer. Further validation demonstrated that overexpression of FADD was positively correlated with the infiltration of Foxp3 in PSCC (p=0.0142). It is the first time to show that overexpression of FADD is an adjunct biomarker with poor prognosis in PSCC and could also serve as a tumor immune environment regulator.

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

First-line programmed death receptor-1 (PD-1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum-based chemotherapy, for stage IV penile cancer.

OBJECTIVES: To evaluate the anti-tumour activity and safety of anti-programmed death receptor-1 (PD-1) antibody plus epidermal growth factor receptor blockade combined with platinum-based chemotherapy (PEP) as first-line therapy for stage IV penile squamous cell carcinoma (PSCC). PATIENTS AND METHODS: We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first-line PEP at Sun Yat-sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Of 17 patients who received first-line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow-up time was 24.87 (3.63-29.40) months. Median PFS and median OS were not reached, with 2-year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7-96.1) and 62.9% (95% CI 41.6-95), respectively. Eight patients experienced Grade 3 or 4 treatment-related AEs. No Grade 5 AEs or death associated with treatment was observed. CONCLUSIONS: Anti-PD-1 antibody plus epidermal growth factor receptor blockade and platinum-based chemotherapy showed promising anti-tumour activity, acceptable toxicity, and satisfying long-term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings.

Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients.

BACKGROUND: To investigate the association between squamous cell carcinoma antigen (SCCAg) level and epidermal growth factor receptor (EGFR) mutation status in Chinese lung adenocarcinoma patients. METHODS: We retrospectively analyzed 293 patients with lung adenocarcinoma, divided into EGFR mutant group (n = 178) and EGFR wild-type group (n = 115). The general data and laboratory parameters of the two groups were compared. We used univariable and multivariable logistic regression to analyze the association between SCCAg level and EGFR mutation. Generalized additive model was used for curve fitting, and a hierarchical binary logistic regression model was used for interaction analysis. RESULTS: Squamous cell carcinoma antigen level in the EGFR wild-type group was significantly higher than that in the mutant group (p < 0.001). After adjusting for confounding factors, we found that elevated SCCAg was associated with a lower probability of EGFR mutation, with an OR of 0.717 (95% CI: 0.543-0.947, p = 0.019). For the tripartite SCCAg groups, the increasing trend of SCCAg was significantly associated with the decreasing probability of EGFR mutation (p for trend = 0.015), especially for Tertile 3 versus Tertile 1 (OR = 0.505; 95% CI: 0.258-0.986; p = 0.045). Curve fitting showed that there was an approximate linear negative relationship between continuous SCCAg and EGFR mutation probability (p = 0.020), which was first flattened and then decreased (p < 0.001). The association between the two was consistent among different subgroups, suggesting no interaction (all p > 0.05). CONCLUSION: There is a negative association between SCCAg level and EGFR mutation probability in Chinese lung adenocarcinoma patients.

RITA1 drives the growth of bladder cancer cells by recruiting TRIM25 to facilitate the proteasomal degradation of RBPJ.

Bladder cancer (BC) is one of the most prevalent malignancies worldwide, but it lacks effective targeted therapy due to its elusive molecular mechanism. Therefore, it is important to further investigate the molecular mechanisms that mediate BC progression. By performing a tumor tissue-based gene microarray and shRNA library screening, we found that recombination signal binding protein for immunoglobulin kappa J region (RBPJ) interacting and tubulin associated 1 (RITA1) is crucial for the growth of BC cells. Moreover, RITA1 is aberrantly highly expressed in BC tissues and is also correlated with poor prognosis in patients with BC. Mechanistically, we determined that RITA1 recruits tripartite motif containing 25 (TRIM25) to ubiquitinate RBPJ to accelerate its degradation via proteasome, which leads to the transcriptional inhibition of Notch1 downstream targets. Our results suggest that aberrant high expression of RITA1 drives the growth of BC cells via the RITA1/TRIM25/RBPJ axis and RITA1 may serve as a promising therapeutic target for BC.

Nkx2.8 promotes chemosensitivity in bladder urothelial carcinoma via transcriptional repression of MDR1.

Multidrug resistance gene 1 (MDR1), a key factor contributing to drug insensitivity, has been associated with treatment failure and poor prognoses in various cancers, including bladder urothelial carcinoma (UC). Here we show that positive Nkx2.8 expression was associated with better prognosis of UC patients received chemotherapy. Patients with positive Nkx2.8 expression had promising prognosis from adjuvant chemotherapy. Enforced expression of Nkx2.8 promotes drug sensitivity of UC cells. Mechanistic investigations showed that Nkx2.8 negatively regulated expression of MDR1 by binds directly to the MDR1 promoter and transcriptionally represses MDR1 expression. P-gp inhibitor reversed chemosensitivity inhibition by Nkx2.8 scilencing. In clinical UC specimens, expression of Nkx2.8 inversely correlated with P-gp expression, and UC patients with Nkx2.8 positivity and low P-gp expression displayed the best prognosis. Our findings uncovered a new mechanism of chemosensitivity in UC cells and proposing Nkx2.8-MDR1 axis as a novel candidate target for therapeutic intervention of UC.