Objective. To explore the correlations of cancer-related fatigue (CRF) with clinicopathological features and quality of life in gastric cancer. Methods. Using a convenient sampling method, 230 patients with gastric cancer admitted to our hospital from March 2020 to July 2022 were collected. They were divided into the fatigue group (n=152) and the nonfatigue group (n=78) according to the presence/absence of CRF. Relevant data were collected and compared. Results. Statistically significant differences were found between the two groups in age ratio (χ2=41.671, P<0.001), T stage ratio (χ2=9.973, P=0.019), N stage ratio (P<0.001), PS score (P<0.001), and the degree of gastric cancer thickening (14.21±3.32 vs. 12.12±3.81 mm, t=4.572, P<0.001). Patients with gastric cancer had the lowest CRF Brief Fatigue Inventory (BFI) score for general activities (2.26±0.37) and high scores for work activities (6.23±0.24) and enjoyment of life (7.11±1.34). Pearson’s correlation analysis revealed a positive correlation between patient emotions and the CRF BFI score (r=0.443, P=0.001). Patients with mild, moderate, and severe CRF showed statistically significant differences in physical functioning (83.34±21.12 vs. 65.23±21.14 vs. 32.25±17.29, F=15.382, P<0.001), role emotional (72.53±21.21 vs. 67.33±27.56 vs. 54.37±26.45, F=14.483, P<0.001), fatigue (49.12±18.44 vs. 54.61±26.64 vs. 67.51±14.27, F=13.581, P<0.001), bodily pain (56.56±25.12 vs. 76.43±21.71 vs. 80.32±12.39, F=14.582, P<0.001), appetite reduction (57.45±25.47 vs. 69.51±16.21 vs. 76.23±27.58, F=14.592, P<0.001), and overall health status and quality of life (67.21±19.45 vs. 53.43±22.32 vs. 43.43±12.52, F=16.494, P<0.001). After chemotherapy, the average CRF BFI scores of the partial remission (PR), disease stability (SD), and disease progression (PD) groups all reduced than those before chemotherapy (all P<0.05). At 3 months of follow-up, a comparison of the average CRF BFI scores with those before chemotherapy revealed a decrease in the SD and PR groups and an increase in the PD group. Conclusion. In conclusion, CRF is correlated with age, T stage, and N stage in gastric cancer. The later the T and N stages, the more significant the effect on fatigue. Moreover, CRF can also affect the quality of life in gastric cancer, and the severer the CRF, the poorer the quality of life.

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0.980 in simulated low-pass WGS data, and obtained a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 1.3 × 10−4, compared with BRCA-intact samples). In ovarian cancer, GSscan obtained higher HRD risk scores in BRCA-deficient samples in both simulated data and clinical samples (p = 2.3 × 10−5 and p = 0.039, respectively, compared with BRCA-intact samples). Moreover, HRD-positive patients predicted by GSscan showed longer progression-free intervals in TCGA datasets (p = 0.0011) treated with platinum-based adjuvant chemotherapy, outperforming existing low-pass WGS-based methods. Furthermore, GSscan can accurately predict HRD status using only 1 ng of input DNA and a minimum sequencing coverage of 0.02 × , providing a reliable, accessible, and cost-effective approach. In summary, GSscan effectively and accurately detected HRD status, and provide a broadly applicable framework for disease diagnosis and selecting appropriate disease treatment.

BackgroundMucosa-associated lymphoid tissue (MALT) lymphoma is a group of extranodal lymphomas that originate from B cells. Primary colonic MALT lymphoma is a rare disease, and there is no consensus on its endoscopic features and standard therapies. It is essential to raise awareness of colonic MALT lymphoma and choose the appropriate treatment. Case presentationIn this case report, we describe a 0-IIb-type lesion that was found by electronic staining endoscopy and magnifying endoscopy. The patient underwent a definitive diagnostic ESD for diagnosis. The patient was evaluated for lymphoma after diagnostic ESD according to the Lugano 2014 evaluation criteria, which are divided into imaging remission on the basis of CT and/or magnetic resonance imaging (MRI) evaluation and metabolic remission on the basis of PET-CT evaluation. Based on the PET-CT results suggesting increased glucose metabolism in the sigmoid colon, the patient underwent additional surgical treatment. According to the pathological results of the surgery, we found that ESD could treat such lesions, which may provide a new option for colorectal MALT lymphoma. ConclusionThe low incidence of colorectal MALT lymphoma, especially for 0-IIb lesions, which are difficult to detect, requires the use of electronic staining endoscopy to improve the detection rate. The combination with magnification endoscopy can improve the understanding of colorectal MALT lymphoma, which ultimately requires pathological support for diagnosis. According to our experience with the present patient case, ESD seems to be a feasible and economical choice for the treatment of massive colorectal MALT lymphoma. However, the combined application of ESD and another therapy scheme needs further clinical investigation.

Homologous recombination repair deficiency (HRD) results in a defect in DNA repair and is a frequent driver of tumorigenesis. Poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum-based therapies have increased theraputic effectiveness when treating HRD positive cancers. For breast cancer and ovairan cancer HRD companion diagnostic tests are commonly used. However, the currently used HRD tests are based on high-depth genome sequencing or hybridization-based capture sequencing, which are technically complex and costly. In this study, we modified an existing method named shallowHRD, which uses low-pass whole genome sequencing (WGS) for HRD detection, and estimated the performance of the modified shallowHRD pipeline. Our shallowHRD pipeline achieved an AUC of 0.997 in simulated low-pass WGS data, with a sensitivity of 0.981 and a specificity of 0.964; and achieved a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 5.5 × 10-5, compared with BRCA-intact breast cancer samples). We also estimated the limit of detection the shallowHRD pipeline could accurately predict HRD status with a minimum sequencing depth of 0.1 ×, a tumor purity of > 20%, and an input DNA amount of 1 ng. Our study demostrates using low-pass sequencing, HRD status can be determined with high accuracy using a simple approach with greatly reduced cost.

BackgroundUnderstanding the association between relative mortality with body mass index (BMI) may aid clinicians in making suitable clinical decisions. Our study evaluated the impact of BMI on mortality among cancer survivors.MethodsWe used data from the US National Health and Nutrition Examination Surveys (NHANES) spanning from 1999 to 2018. Relevant mortality data were retrieved up until December 31, 2019. Adjusted Cox models were employed to examine the association of BMI with the risks for total and cause-specific mortality.ResultsAmong 4135 cancer survivors, 1486 (35.9%) were obese (21.0% class 1 obesity [BMI 30-< 35 kg/m2], 9.2% class 2 obesity [BMI 35 -< 40 kg/m2], 5.7% class 3 obesity [BMI ≥ 40 kg/m2]), 1475(35.7%) were overweight (BMI 25-< 30 kg/m2). During an average follow-up of 8.9 years (35895 person-years), a total of 1361 deaths were reported (cancer 392; 356 cardiovascular disease [CVD]; 613, non-cancer, non-CVD). In multivariable models, underweight participants (BMI < 18.5 kg/m2) were associated with significantly higher risks of cancer-specific (HR, 3.31; 95% CI, 1.37-8.03, P=0.01) and CVD cause (HR, 3.18; 95% CI, 1.44-7.02, P < 0.001) mortality compared to individuals with normal weight. Being overweight was associated with significantly lower risks of non-cancer, non-CVD cause mortality (HR, 0.66; 95% CI, 0.51-0.87, P < 0.001). Class 1 obesity was associated with significantly reduced risks of all-cause (HR, 0.78; 95% CI, 0.61-0.99, P = 0.04), and non-cancer, non-CVD cause (HR, 0.60; 95% CI, 0.42-0.86, P = 0.01) mortality. A higher risk of CVD-related mortality (HR, 2.35; 95% CI, 1.07-5.18, P = 0.03) was observed in class 3 obesity cases. Lower risks of all-cause mortality were detected in men (overweight, HR, 0.76; 95% CI, 0.59-0.99, P=0.04; class 1 obesity, HR, 0.69; 95% CI, 0.49-0.98, P = 0.04) but not in woman, in never-smokers (class 1 obesity, HR, 0.61; 95% CI, 0.41-0.90, P=0.01) and former smokers (overweight, HR, 0.77; 95% CI, 0.60-0.98, P=0.04) but not in current smokers; in obesity-related cancer (class 2 obesity, HR, 0.49; 95% CI, 0.27-0.89, P=0.01) but not in non-obesity-related cancers.ConclusionsIn the United States, cancer survivors with overweight or moderate obesity (class 1 or class 2 obesity) demonstrated a lower risk of all-cause and noncancer, non-CVD cause mortality.

Background: Gastric cancer (GC) is a common cancer with a high incidence and mortality rate. Herein, the role of hsa_circ_0002019 (circ_0002019) in GC was investigated.Methods: The molecular structure and stability of circ_0002019 were identified by RNase R, and Actinomycin D treatment. Molecular associations were verified by RIP. Proliferation, migration, and invasion were detected by CCK-8, EdU, and Transwell, respectively. The effect of circ_0002019 on tumor growth was analyzed in vivo.Results: Circ_0002019 was elevated in GC tissues and cells. Circ_0002019 knockdown inhibited the proliferation, migration, and invasion. Mechanically, circ_0002019 activated NF-?B signaling by increasing TNFAIP6 mRNA stability by PTBP1. Activation of NF-?B signaling limited the antitumor effect of circ_0002019 silencing in GC. Circ_0002019 knockdown inhibited tumor growth in vivo by reducing TNFAIP6 expression.Conclusions: Circ_0002019 accelerated the proliferation, migration, and invasion by regulating TNFAIP6/NF-?B pathway, suggesting circ_0002019 could be a key regulatory factor in GC progression.

Background Cancer screening and early detection greatly increase the chances of successful treatment. However, most cancer types lack effective early screening biomarkers. In recent years, natural language processing (NLP)-based text-mining methods have proven effective in searching the scientific literature and identifying promising associations between potential biomarkers and disease, but unfortunately few are widely used. Methods In this study, we used an NLP-enabled text-mining system, MarkerGenie, to identify potential stool bacterial markers for early detection and screening of colorectal cancer. After filtering markers based on text-mining results, we validated bacterial markers using multiplex digital droplet polymerase chain reaction (ddPCR). Classifiers were built based on ddPCR results, and sensitivity, specificity, and area under the curve (AUC) were used to evaluate the performance. Results A total of 7 of the 14 bacterial markers showed significantly increased abundance in the stools of colorectal cancer patients. A five-bacteria classifier for colorectal cancer diagnosis was built, and achieved an AUC of 0.852, with a sensitivity of 0.692 and specificity of 0.935. When combined with the fecal immunochemical test (FIT), our classifier achieved an AUC of 0.959 and increased the sensitivity of FIT (0.929 vs. 0.872) at a specificity of 0.900. Conclusions Our study provides a valuable case example of the use of NLP-based marker mining for biomarker identification.

BACKGROUND:Differential diagnosis of colorectal intramucosal tumors from invasive adenocarcinoma is important in clinical practice due to the different risks of lymph node metastasis and different treatment options. The phenomenon of a colorectal adenoma with part of the gland entering the submucosa is known as pseudoinvasion of the adenoma, which is a major challenge for pathological diagnosis. It is essential to raise awareness of colorectal adenoma with submucosal pseudoinvasion clinically to avoid overtreatment.CASE SUMMARY:We describe a case of rectal adenoma with submucosal pseudoinvasion in a 48-year-old man. The patient was admitted to Jinhua People's Hospital due to a change in stool habit for 5 d. We performed colonoscopy, and the results suggested a submucosal bulge approximately 1.0 cm × 1.0 cm in size in the rectum 8 cm from the anal verge, with red surface erosion. Ultrasound colonoscopy was also performed and a homogeneous hypoechoic mass about 0.52 cm × 0.72 cm in size was seen at the lesion, protruding into the lumen with clear borders and invading the submucosa. Endoscopic surgery was then performed and the pathological specimen showed a tubular adenoma with high-grade intraepithelial neoplasia (intramucosal carcinoma) involving the adenolymphatic complex. In addition, we performed a literature review of rectal tubular adenoma with submucosal pseudoinvasion to obtain a deeper understanding of this disease.CONCLUSION:The aim of this study was to improve awareness of this lesion for clinicians and pathologists to reduce misdiagnosis.

Defects in BRCA1, BRCA2 and other genes of the homology-dependent DNA repair (HR) pathway cause an elevated rate of mutagenesis, eliciting specific mutation patterns including COSMIC signature SBS3. Using genome sequencing of knock-out cell lines we show that Y family translesion synthesis (TLS) polymerases contribute to the spontaneous generation of base substitution and short insertion/deletion mutations in BRCA1 deficient cells, and that TLS on DNA adducts is increased in BRCA1 and BRCA2 mutants. The inactivation of 53BP1 in BRCA1 mutant cells markedly reduces TLS-specific mutagenesis, and rescues the deficiency of template switch-mediated gene conversions in the immunoglobulin V locus of BRCA1 mutant chicken DT40 cells. 53BP1 also promotes TLS in human cellular extracts in vitro. Our results show that HR deficiency-specific mutagenesis is largely caused by TLS, and suggest a function for 53BP1 in regulating the choice between TLS and error-free template switching in replicative DNA damage bypass.

Translesion DNA synthesis (TLS) is a fundamental damage bypass pathway that utilises specialised polymerases with relaxed template specificity to achieve replication through damaged DNA. Misinsertions by low fidelity TLS polymerases may introduce additional mutations on undamaged DNA near the original lesion site, which we termed collateral mutations. In this study, we used whole genome sequencing datasets of chicken DT40 and several human cell lines to obtain evidence for collateral mutagenesis in higher eukaryotes. We found that cisplatin and UVC radiation frequently induce close mutation pairs within 25 base pairs that consist of an adduct-associated primary and a downstream collateral mutation, and genetically linked their formation to TLS activity involving PCNA ubiquitylation and polymerase κ. PCNA ubiquitylation was also indispensable for close mutation pairs observed amongst spontaneously arising base substitutions in cell lines with disrupted homologous recombination. Collateral mutation pairs were also found in melanoma genomes with evidence of UV exposure. We showed that collateral mutations frequently copy the upstream base, and extracted a base substitution signature that describes collateral mutagenesis in the presented dataset regardless of the primary mutagenic process. Using this mutation signature, we showed that collateral mutagenesis creates approximately 10-20% of non-paired substitutions as well, underscoring the importance of the process.

Introduction Cancer is a genetic modification disease. Since genetic aberrations of gastric cancer are heterogeneous, we assume non-coding RNAs play major roles on gastric cancer phenotypes. Long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is related with poor prognosis in different cancer types, however, how it works in gastric cancer is unknown. Methods Two gastric cancer cell lines are chosen, MNK45 and SGC-7901. Transforming growth factor-β (TGF-β) is used to promote epithelial-mesenchymal transition (EMT) by using cancer cell invasion assay. The transmembrane cell quantities are counted and ZEB1, slug, vimentine and E-Cadherin gene expression levels are measured by quantitative PCR assay. siRNA of UCA1 and miR-204 are used to confirm cross-talk among TGF-β, UCA1 and miR-204. Results TGF-β significantly increases gastric cancer cell transmembrane ability and expression levels of four EMT related genes. These increases can be counteracted by using siRNA of UCA1, suggesting that UCA1 is up-stream factor of TGF-β signaling pathways and positively regulates it. miRNA-204 alone can inhibit ZEB1 gene expression, however, this inhibition can be demolished by UCA1, suggesting that UCA1 sponges miR-204 to prevent its function from inhibiting ZEB1. Conclusions miR-204 could be used as an indicator of prognosis of gastric cancer. The higher miR-204 expression levels, the less possibility to develop EMT. Meanwhile, UCA1 inhibitors can be considered as potential genetic medical drugs.

子痫前期( preeclampsia,PE)是妊娠期常见且特有的并发症,发生率为3 ％ ～5 ％. 主要临床表现为妊娠20周后,出现高血压、蛋白尿及全身器官功能损害. 常引起胎儿宫内缺氧和生长受限,是导致孕产妇和围产儿死亡的重要原因[1-2].

Background Homologous recombination (HR) repair deficiency arising from defects in BRCA1 or BRCA2 is associated with characteristic patterns of somatic mutations. In this genetic study, we ask whether inactivating mutations in further genes of the HR pathway or the DNA damage checkpoint also give rise to somatic mutation patterns that can be used for treatment prediction. Results Using whole genome sequencing of an isogenic knockout cell line panel, we find a universal HR deficiency-specific base substitution signature that is similar to COSMIC signature 3. In contrast, we detect different deletion phenotypes corresponding to specific HR mutants. The inactivation of BRCA2 or PALB2 leads to larger deletions, typically with microhomology, when compared to the disruption of BRCA1, RAD51 paralogs, or RAD54. Comparison with the deletion spectrum of Cas9 cut sites suggests that most spontaneously arising genomic deletions are not the consequence of double-strand breaks. Surprisingly, the inactivation of checkpoint kinases ATM and CHK2 has no mutagenic consequences. Analysis of tumor exomes with biallelic inactivating mutations in the investigated genes confirms the validity of the cell line models. We present a comprehensive analysis of sensitivity of the investigated mutants to 13 therapeutic agents for the purpose of correlating genomic mutagenic phenotypes with drug sensitivity. Conclusion Our results suggest that no single genomic mutational class shows perfect correlation with sensitivity to common treatments, but the contribution of COSMIC signature 3 to base substitutions, or a combined measure of different features, may be reasonably good at predicting platinum and PARP inhibitor sensitivity.

The mesenchymal (MES) subtype of glioblastoma (GBM) stem cells (GSCs) represents a subpopulation of cancer cells that are notorious for their highly aggressive nature and resistance to conventional therapy. Aldehyde dehydrogenase 1A3 (ALDH1A3) has been recently suggested as a key determinant for the maintenance of MES features of GSCs. However, the mechanisms underpinning aberrant ALDH1A3 expression remain elusive. Here, we identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of ALDH1A3 in MES GSCs. USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, we showed that FACS-sorted USP9Xhi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. Depletion of USP9X markedly downregulated ALDH1A3, resulting in a loss of self-renewal and tumorigenic capacity of MES GSCs, which could be largely rescued by ectopic expression of ALDH1A3. Furthermore, we demonstrated that the USP9X inhibitor WP1130 induced ALDH1A3 degradation and showed marked therapeutic efficacy in MES GSC-derived orthotopic xenograft models. Additionally, USP9X strongly correlated with ALDH1A3 expression in primary human GBM samples and had a prognostic value for patients with the MES subgroup. Collectively, our findings unveil USP9X as a key deubiquitinase for ALDH1A3 protein stabilization and a potential target for GSC-directed therapy.

DEPDC1 (DEP domain containing 1) is overexpressed in multiple cancers and is associated with cell cycle progression. In this report, we have investigated the expression, localization, phosphorylation and function of DEPDC1 during mitosis. DEPDC1 has two isoforms (isoform a and isoform b), and both of them are increased in mitosis and degraded once cells exit mitosis. DEPDC1a is localized to the centrosome in metaphase, whereas DEPDC1b is localized to the entire cell cortex during mitosis. DEPDC1a, but not DEPDC1b, was required for the integrity of centrosome and organization of the bipolar spindle. Mass spectrometry and biochemical analyses revealed phosphorylation of DEPDC1 at Ser110. The phosphorylation of Ser110 is essential for localization of DEPDC1a to the centrosome. Consistently, non-phosphorylation mutants of DEPDC1a did not rescue disruption of centrosome organization by depletion of endogenous DEPDC1. Our results show a novel role for DEPDC1 in maintaining centrosome integrity during mitosis for the accurate distribution of chromosomes.

习惯性流产(RSA)定义为孕前20周连续3次或以上的流产.细胞因子是一类能在细胞间传递信息、具有免疫调节和效应功能的蛋白质或小分子多肽,影响妊娠的各个阶段,对妊娠结局起到至关重要的作用.鉴于细胞因子在母-胎免疫调节中的重要作用以及遗传多态对细胞因子功能和表达水平的潜在影响,近年来细胞因子遗传多态与复发性流产的关联研究成为国际研究的热点.这类研究目前存在诸多问题:不同研究关联结果不一致甚至相悖,细胞因子多态性在RSA中的作用难以确定;多在一项研究中发现少数的阳性报道,缺乏其他人群的验证,有假阳性的风险;病例-对照研究样本量小(＜ 400例),统计效能偏低,容易造成假阴性结果;对于一个基因遗传多态位点研究不全面,极可能错过真正的致病位点;忽视了基因-基因交互作用和环境-基因交互作用对RSA的影响.因此,扩大样本规模、全面系统地研究细胞因子基因上代表性遗传多态,探讨基因-基因和基因-环境交互作用对复发性流产的影响,成为该研究领域的迫切需求.

Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT) 1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine-and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.

Dynamic changes in microtubule organization are regulated by numerous microtubule‐associating proteins and their post‐translational modification. Microtubule crosslinking factor 1 (MTCL1) is a recently identified protein that regulates microtubule organization. To obtain further insight into its functions, we searched for proteins that associate with it using mass spectrometry analysis. We found that PPP2R5E, a regulatory subunit of protein phosphatase 2A, interacted with MTCL1. Depletion of PPP2R5E reduced the abundance of MTCL1 abundance, whereas exogenous expression of PPP2R5E increased endogenous MTCL1. Furthermore, inhibition of phosphatase activity by okadaic acid reduced MTCL1, which was restored by the addition of the protease inhibitor MG132. Finally, we show that cells depleted of PPP2R5E and MTCL1 exhibited defects in microtubule organization. Our results suggest that the PPP2R5E phosphatase may contribute to microtubule organization by stabilizing MTCL1.

Homeoproteins, a family of transcription factors that have conserved homeobox domains, play critical roles in embryonic development in a wide range of species. Accumulating studies have revealed that homeoproteins are aberrantly expressed in multiple tumors and function as either tumor promoters or suppressors. In this study, we show that two homeoproteins, HOXB13 and ALX4, are associated with epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells. HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either protein promoted EMT and invasion. Conversely, depletion of either protein suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13 or ALX4 suppressed SLUG expression, and exogenous expression of either protein promoted SLUG expression. Finally, we showed that SLUG expression was essential for the HOXB13- or ALX4-mediated EMT and invasion. Our results show that HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion of ovarian cancer cells.