A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Adherence to Treatment and Follow-Up of Precancerous Cervical Lesions in Ethiopia.

BACKGROUND: In Ethiopia, both incidence and mortality of cervical cancer are relatively high. Screening services, which were implemented during the past few years, are currently being expanded. The World Health Organization recommends patients with a positive VIA (visual inspection with acetic acid) result should immediately receive treatment followed by rescreening after 1 year as precancerous lesions can reoccur or become residential despite treatment. MATERIALS AND METHODS: Screening logbooks dating between 2017 and 2020 were retrospectively reviewed in 14 health facilities of Addis Ababa and Oromia region. Data for 741 women with a VIA-positive result were extracted and those women were asked to participate in a questionnaire-based phone interview to gain insights about adherence to treatment and follow-up. Data were analyzed using descriptive methods and then fitted into 2 generalized linear models to test variables for an influence on adherence to follow up. RESULTS: Around 13 800 women had received a VIA screening, of which approximately 820 (5.9%) were VIA positive. While over 90% of women with a positive screen received treatment, only about half of the treated patients returned for a follow-up examination. After treatment, 31 women had a VIA-positive re-screen. We found that educational status, age over 40, no/incorrect follow-up appointment, health facility-related barriers, and use of reminders are important drivers of adherence to follow up. CONCLUSION: Our results revealed that adherence to treatment after VIA positive screening is relatively high whereas adherence to follow up recommendations still needs improvement. Reminders like appointment cards and phone calls can effectively reduce the loss of follow-up.

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study.

BACKGROUND: The Correa's cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa's cascade are scarce. METHODS: We compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979-2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison. RESULTS: A total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08-1.14) for the normal mucosa group to 1.54 (95% CI 1.46-1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa's cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for "infectious diseases and parasitic diseases", "respiratory system diseases", and "digestive system disease", when using the normal mucosa group as reference. CONCLUSIONS: Increased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Precision therapy for cancer prevention by targeting carcinogenesis.

Cancer represents a major global public health burden, with new cases estimated to increase from 14 million in 2012 to 24 million by 2035. Primary prevention is an effective strategy to reduce the costs associated with cancer burden. For example, measures to ban tobacco consumption have dramatically decreased lung cancer incidence and vaccination against human papillomavirus can prevent cervical cancer development. Unfortunately, the etiological factors of many cancer types are not completely clear or are difficult to actively control; therefore, the primary prevention of such cancers is not practical. In this review, we update the progress on precision therapy by targeting the whole carcinogenesis process, especially for three high-risk groups: (1) those with chronic inflammation, (2) those with inherited germline mutations, and (3) those with precancerous lesions like polyps, gastritis, actinic keratosis or dysplasia. We believe that attenuating chronic inflammation, treating precancerous lesions, and removing high-risk tissues harboring germline mutations are precision methods for cancer prevention.

Role of Hippo pathway dysregulation from gastrointestinal premalignant lesions to cancer.

BACKGROUND: First identified in Drosophila melanogaster, the Hippo pathway is considered a major regulatory cascade controlling tissue homeostasis and organ development. Hippo signaling components include kinases whose activity regulates YAP and TAZ final effectors. In response to upstream stimuli, YAP and TAZ control transcriptional programs involved in cell proliferation, cytoskeletal reorganization and stemness. MAIN TEXT: While fine tuning of Hippo cascade components is essential for maintaining the balance between proliferative and non-proliferative signals, pathway signaling is frequently dysregulated in gastrointestinal cancers. Also, YAP/TAZ aberrant activation has been described in conditions characterized by chronic inflammation that precede cancer development, suggesting a role of Hippo effectors in triggering carcinogenesis. In this review, we summarize the architecture of the Hippo pathway and discuss the involvement of signaling cascade unbalances in premalignant lesions of the gastrointestinal tract, providing a focus on the underlying molecular mechanisms. CONCLUSIONS: The biology of premalignant Hippo signaling dysregulation needs further investigation in order to elucidate the evolutionary trajectories triggering cancer inititation and develop effective early therapeutic strategies targeting the Hippo/YAP pathway.

miR-129-5p inhibits anchorage-independent growth through silencing of ACTN1 and the ELK4/c-FOS axis in HPV-transformed keratinocytes.

A persistent infection with human papillomavirus (HPV) can induce precancerous lesions of the cervix that may ultimately develop into cancer. Cervical cancer development has been linked to altered microRNA (miRNA) expression, with miRNAs regulating anchorage-independent growth being particularly important for the progression of precancerous lesions to cancer. In this study, we set out to identify and validate targets of miR-129-5p, a previously identified tumor suppressive miRNA involved in anchorage-independent growth and HPV-induced carcinogenesis. We predicted 26 potential miR-129-5p targets using online databases, followed by KEGG pathway enrichment analysis. RT-qPCR and luciferase assays confirmed that 3'UTR regions of six genes (ACTN1, BMPR2, CAMK4, ELK4, EP300, and GNAQ) were targeted by miR-129-5p. Expressions of ACTN1, CAMK4, and ELK4 were inversely correlated to miR-129-5p expression in HPV-transformed keratinocytes, and their silencing reduced anchorage-independent growth. Concordantly, miR-129-5p overexpression decreased protein levels of ACTN1, BMPR2, CAMK4 and ELK4 in anchorage-independent conditions. Additionally, c-FOS, a downstream target of ELK4, was downregulated upon miR-129-5p overexpression, suggesting regulation through the ELK4/c-FOS axis. ACTN1 and ELK4 expression was also upregulated in high-grade precancerous lesions and cervical cancers, supporting their clinical relevance. In conclusion, we identified six targets of miR-129-5p involved in the regulation of anchorage-independent growth, with ACTN1, BMPR2, ELK4, EP300, and GNAQ representing novel targets for miR-129-5p. For both ACTN1 and ELK4 functional and clinical relevance was confirmed, indicating that miR-129-5p-regulated ACTN1 and ELK4 expression contributes to HPV-induced carcinogenesis.

Unraveling cervical cancer screening dilemmas: histopathological insights from VIA and LEEP at bugando medical centre, Mwanza.

BACKGROUND: The single-visit strategy, also known as the "screen-and-treat" approach, is widely used to screen for cervical cancer in low- and middle-income countries. The screen-and-treat approach leads to unnecessary or inadequate treatment. Thus, a study was conducted to determine the histopathological patterns of aceto-white lesions on visual inspection with acetic acid (VIA) in patients who underwent a Loop Electrosurgical Excision Procedure (LEEP) at Bugando Medical Centre between January 2016 and December 2020. METHOD: A 5-year retrospective cross-sectional case record review was conducted on 329 women who had LEEP at Bugando Medical Centre following a positive VIA cervical screening test. A standard data abstraction form was used to collect patient information. Missing client information records and LEEP without histopathological results were exclusion criteria. For statistical analysis, STATA version 15 was used; in descriptive statistics, frequency, mean, and standard deviation were used. The Chi2 and Fisher's exact tests were used to investigate the relationship between patient characteristics and histopathological patterns, and a P-value of 0.05 was considered statistically significant in multinomial models. RESULTS: This study looked at 329 patients who had LEEP following a VIA positive but were not eligible for cryotherapy. Our study participants had a mean age of 40 ± 8.2 SD. There were 203 (61.7%) patients with benign lesions, including 4 with schistosomiasis and 2 with cervical tuberculosis. The precancerous lesions were discovered in 100 cases (30.4%), and 26 (7.9%) already had invasive cervical cancer. Out of 100 patients with precancerous lesions, 58 (17.6%) and 42 (12.8%) have high- and low-grade squamous intraepithelial (HSIL and LSIL) lesions, respectively. The presence of a precancerous lesion was found to be associated with age 31-40 years (P-value 0.042) and HIV positivity (P-value 0.004). CONCLUSION: Most patients in this study had benign cervical lesions, which do not require LEEP treatment. Nonetheless, a considerable percentage of invasive cervical malignancies and rare benign diseases such as schistosomiasis and cervical tuberculosis were identified. A screen-and-treat approach within well-equipped tertiary hospitals like Bugando Medical Centre should explore alternative options instead of relying solely on straight LEEP.

The insufficiency of CT examination in early detection of central lung squamous cell carcinoma and squamous epithelial precancerous lesions.

BACKGROUND: CT examination for lung cancer has been carried out for more than 20 years and great achievements have been made in the early detection of lung cancer. However, in the clinical work, a large number of advanced central lung squamous cell carcinoma are still detected through bronchoscopy. Meanwhile, a part of CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions are also accidentally detected through bronchoscopy. METHODS: This study retrospectively collects the medical records of patients in the bronchoscopy room of the Endoscopy Department of Zhejiang Cancer Hospital from January 2014 to December 2018. The inclusion criteria for patients includes: 1.Patient medical records completed, 2.Without history of lung cancer before the diagnosis and first pathological diagnosis of primary lung cancer, 3.Have the lung CT data of the same period, 4.Have the bronchoscopy records and related pathological diagnosis, 5.The patients undergoing radical surgical treatment must have a complete postoperative pathological diagnosis. Finally, a total of 10,851 patients with primary lung cancer are included in the study, including 7175 males and 3676 females, aged 22-98 years. Firstly, 130 patients with CT-occult lesions are extracted and their clinical features are analyzed. Then, 604 cases of single central squamous cell carcinoma and 3569 cases of peripheral adenocarcinoma are extracted and compares in postoperative tumor diameter and lymph node metastasis. RESULTS: 115 cases of CT-occult central lung squamous cell carcinoma and 15 cases of squamous epithelial precancerous lesions are found. In the total lung cancer, the proportion of CT-occult lesions is 130/10,851 (1.20%). Meanwhile, all these patients are middle-aged and elderly men with a history of heavy smoking. There are statistically significant differences in postoperative median tumor diameter (3.65 cm vs.1.70 cm, P < 0.0001) and lymph node metastasis rate (50.99% vs.13.06%, P < 0.0001) between 604 patients with operable single central lung squamous cell carcinoma and 3569 patients with operable peripheral lung adenocarcinoma. Of the 604 patients with squamous cell carcinoma, 96.52% (583/604) are male with a history of heavy smoking and aged 40-82 years with a median age of 64 years. CONCLUSIONS: This study indicates that the current lung CT examination of lung cancer is indeed insufficiency for the early diagnosis of central squamous cell carcinoma and squamous epithelial precancerous lesions. Further bronchoscopy in middle-aged and elderly men with a history of heavy smoking can make up for the lack of routine lung CT examination.

Endoscopic Kyoto and Kimura-Takemoto Classifications Are Comparable in Predicting High-Risk Gastric Precancerous Lesions.

INTRODUCTION: Severe and extensive gastric atrophy, extensive or incomplete gastric intestinal metaplasia, and gastric dysplasia are considered high-risk gastric precancerous lesions (HGPLs). Endoscopic findings based on the endoscopic Kyoto classification (EKC) and the Kimura-Takemoto classification (KTC) have been reported to be significantly associated with HGPLs. This study aimed to compare these two classifications in predicting active Helicobacter pylori (H. pylori) infection and HGPLs. METHODS: This is a cross-sectional study conducted on naïve dyspeptic patients who underwent upper gastrointestinal endoscopy at a tertiary hospital. Endoscopic findings were scored according to the EKC and KTC. Mapping biopsies were taken, and H. pylori infection was determined using a locally validated rapid urease test and histology. The performance of EKC was compared with that of KTC using the area under the receiver operating characteristic curve (AUC) in predicting active H. pylori infection and HGPLs. RESULTS: There were 292 patients with a median age of 46 and a male-to-female ratio of 1:1. The rates of active H. pylori infection and HGPLs were 61.3% and 14.0%, respectively. The EKC was better than the KTC in predicting active H. pylori infection (AUC: 0.771 vs. 0.658, respectively; p < 0.001). However, these two classifications had comparable performance in predicting HGPLs (AUC: 0.792 vs. 0.791, respectively; p = 0.956). CONCLUSION: Compared to EKC, KTC is inferior in predicting active H. pylori infection but has comparable performance in predicting HGPLs.

A risk prediction model for delayed bleeding after ESD for gastric precancerous lesions.

OBJECTIVE: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model. METHODS: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model. RESULTS: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability. CONCLUSION: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients.

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

Dyslipidemia: prevalence and association with precancerous and cancerous lesions of the cervix; a pilot study.

BACKGROUND: In Sub-Saharan Africa, the prevalence of dyslipidemia is on the rise, with studies showing dyslipidemia as a contributing factor to the progression of premalignant lesions to cervical cancer. In Uganda, cervical cancer and dyslipidemia are common health concerns, considering the increasing trends of dyslipidemia in the general population and inadequate information regarding dyslipidemia and cervical lesions. This study aimed to determine the prevalence of dyslipidemia and its association with precancerous and cancerous lesions of the cervix among women attending a cervical cancer clinic at the Uganda Cancer Institute. METHODS: This cross-sectional study was conducted from February to April 2022 among women with premalignant and malignant lesions of the cervix. Data on social demographics and health-seeking behaviours were collected using a pretested structured questionnaire after written informed consent had been obtained. Pap smear collection preceded visual inspection with acetic acid; cervical biopsies were collected appropriately from eligible participants; and cervical lesions were classified using the Bethesda system 2014. Serum lipids, total cholesterol (T.C.), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc), and triglycerides (T.G.s) were analysed using the COBAS™ 6000 Clinical Chemistry Analyser. The associations were assessed using the chi-square test, and P ≤ 0.05 was considered statistically significant. RESULTS: The overall prevalence of dyslipidemia among women with cervical lesions was 118/159 (74%), and low HDLc was the most prevalent at 64.6% (95% CI 39.0-54.3). High T.C. (P = 0.05), high T.G.s (P = 0.011), and low HDL-c (P = 0.05) showed a significant association with precancerous lesions. High LDL-c (P = 0.019), high T.G.s (P = 0.02), and high T.G.s (P < 0.001) showed a statistically significant association with cancerous lesions. CONCLUSION: The prevalence of dyslipidemia was high, with high TC, T.G.s, and low HDL-c significantly associated with precancerous lesions. Also, elevated T.G.s and high LDLc were significantly associated with cancerous lesions. Women may benefit from dyslipidemia screening along with cervical cancer screening. WHAT THIS STUDY ADDS: The present study builds upon previous findings suggesting a link between dyslipidemia and cervical lesions by investigating the relationship between these two factors, specifically in women of this geographical location, where we need adequate information on these associations.

Application of narrow band imaging in the diagnosis of pharyngeal tumors.

BACKGROUND: Narrow-band imaging (NBI) endoscopy is used in various tumor detection and is important in detecting early tumors. OBJECTIVE: To explore the application value of NBI endoscopy in diagnosing pharyngeal tumors. MATERIAL AND METHODS: Ninety-one patients with pharyngeal masses who attended the Department of Otorhinolaryngology, Head and Neck Surgery in Gansu Provincial Hospital from January 2023 to February 2024 were selected, and NBI and white light (WL) endoscopy were applied to examine the pharynx and the relationship between the two was observed. SPSS 25.0 software was used for statistical analysis. RESULTS: The sensitivity of NBI endoscopy for diagnosing laryngeal malignant lesions was 92.0 %, the specificity was 93.0 %, the positive predictive value was 88.5 %, and the negative predictive value was 95.2 %, with a high degree of concordance between the results of NBI endoscopy and the pathology; WL endoscopy had a sensitivity of 64.0 %, a specificity of 76. 7 %, a positive predictive value of 61.5 %, and a negative predictive value of 78.6 %, with WL endoscopic findings had moderate concordance with pathology. The diagnostic accuracy of NBI endoscopy was higher than that of WL endoscopy for both benign and malignant lesions and precancerous lesions. CONCLUSION: NBI endoscopy can detect laryngeal cancer lesions more accurately.

Machine learning-driven SERS analysis platform for rapid and accurate detection of precancerous lesions of gastric cancer.

A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement-based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas-liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC.

Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting seed-matching and the reverse interplay between miRNA levels and their target genes' expression. Incorporating gene-expression data from our group's experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia, and early invasion, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is under-expressed in dysplasia and early invasion. The malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p, and miR-34a-5p. The identification of stage-specific miRNAs may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Incidence of cervical precancerous lesions and cervical cancer in Denmark from 2000 to 2019: Population impact of multi-cohort vaccination against human papillomavirus infection.

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch-up cohorts (October 2008 in girls 13-15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000-2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age-standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000-2005), early after implementation of childhood HPV vaccination and the first catch-up vaccination program (2006-2012), and after implementation of the second catch-up program (2013-2019). For CIN3 and AIS, age-specific incidence rates and EAPCs were calculated. An increasing age-standardized incidence was observed before introduction of HPV vaccination (2000-2005) for CIN3 [EAPCCIN3 : 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPCAIS : 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013-2019), following implementation of the second catch-up program, a decrease was observed for both CIN3 [EAPCCIN3 : -6.5 (95% CI -8.3 to -4.8)], AIS [EAPCAIS : -8.7 (95% CI -12.3 to -5.1)] and for SCC [EAPCSCC : -3.9 (95% CI -7.5 to -0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi-cohort HPV vaccination in Denmark.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk.

OBJECTIVES: Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. METHODS: In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. RESULTS: Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). CONCLUSION: In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.