Establishment and validation of a risk prediction model for sarcopenia in gastrointestinal cancer patients: A systematic review and meta-analysis-based approach.

OBJECTIVE: The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia. METHODS: This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model. RESULTS: The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847. CONCLUSIONS: The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia.

PROTACs in gynecological cancers: Current knowledge and future potential as a treatment strategy.

Cancer continues to threaten human health regardless of novel therapeutic options. Over the last two decades, targeted therapy has emerged as a significant advancement in treating malignancies, surpassing standard chemoradiotherapy and surgical procedures. Gynecological malignancies, including cervical, endometrial, and ovarian carcinoma, have a bad prognosis in advanced or metastatic stages and are difficult to treat. The advancements in understanding the molecular pathways behind cancer development offer valuable insights into promising targeted medicines, and researchers have always searched for a superior and safe technique to target cancer-related oncoproteins because of the limited therapeutic benefit, drug resistance, and off-target effects of current targeted treatments. Recently, proteolysis-targeting chimeras (PROTACs) have been developed to selectively degrade proteins using the natural ubiquitin-proteasome system (UPS). These approaches have garnered significant attention in the field of cancer research. The rapid progress in PROTACs has also eased the targeting of various oncoproteins in gynecological cancer. Therefore, this review aims to elucidate the mechanism and research advancements of PROTACs and provide a comprehensive overview of their use in gynecological tumors.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers.

BACKGROUND: Immunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear. METHODS: We retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC. Clinical outcomes including tumor response and patient survival were assessed. Kaplan-Meier curves with the log-rank test were employed to compare survival data. Cox regression analysis was utilized to investigate prognostic factors. RESULTS: A total of 65 R/M CC patients treated with immune checkpoint inhibitors were eligible for analysis. We found that immunotherapy combined with palliative radiotherapy showed a significant positive correlation with complete response (OR = 6.31; 95 %CI: 1.74-22.91; p = 0.005). The 36-month progression-free survival (PFS) rate (73.7 % vs 33.8 %, p = 0.0048) and 36-month overall survival (OS) rate (85.7 % vs 38.7 %, p = 0.0043) were also prominently increased. We further demonstrated that patients prolonged 36-month PFS rate (69.9 % vs 15.2 %; p < 0.001) and 36-month OS rate (64.6 % vs 39.7 %; p = 0.032) when they had more than 4 cycles of immunotherapy. Meanwhile, our findings showed that patients with only recurrence had longer 36-month OS rate (77.7 % vs 44.4 % vs 40.1 %; p = 0.024) compared to those with only metastasis and both. We also observed that patients with squamous carcinoma had higher 2-year PFS rate (57.9 % vs 14.6 %; p = 0.042) than those with other pathological subtypes (adenocarcinoma, adenosquamous carcinoma and neuroendocrine carcinoma). CONCLUSIONS: The combination of immunotherapy and palliative radiotherapy increased complete response rates and improved survivals in recurrent or metastatic cervical cancer patients.

Clinical trials involving rare gynaecological cancers.

Clinical trials that investigate therapies for rare gynaecological cancers (RGC) are essential to provide evidence-based data towards new effective and safe treatments, however, they present unique challenges. The main objective of this narrative review is to summarize completed phase III clinical trials investigating therapies for RGC and to discuss the outcomes of these trials. PRISMA guidelines were used to report the steps of the review. We searched the WHO's International Clinical Trials Registry Platform, clinicaltrials.gov and PubMed/Medline for publications reporting results from clinical trials on RGC including at least one medication. From 31 identified phase III clinical trials, 13 were still ongoing, four were terminated and just eight (25.8 %) had posted results and/or publications. The latter completed trials were mostly multi-center and located in at least two continents, participants were mainly adults, and the recruitment period varied from about 2.5 to 10.5 years. Allocation was randomized with parallel assignment in 7 out of 8 trials, while only one trial had double masking. The most common primary outcome measure was progression-free survival (PFS), followed by overall survival (OS). Patient-reported outcomes were secondary outcome measures in four completed trials, assessing quality of life by various questionnaires. Most of the trials did not meet their primary endpoints. By highlighting the scarcity of clinical trials on RGC, our findings further emphasize the need for designing, conducting and sustaining phase III clinical trials to investigate innovative therapies for these conditions and report meaningful outcome measures.

Prognosis of hepatocellular carcinoma using the albumin to alkaline phosphatase ratio, literature review, and meta-analysis.

Background: Data about the impact of albumin-to-alkaline phosphatase ratio (AAPR) on prognosis in hepatocellular cancer (HCC) patients are inconclusive and conflicting. Methods: The authors systematically searched literatures from seven databases (PubMed, Medline, Web of Science, Cochrane Library, Embase, Google Scholar, and CINAHL), updated to September 2023. Hazard ratios (HRs) and 95% CIs were pooled and synthesized using Comprehensive Meta-Analysis version 3 in order to assess the overall impact of AAPR on patient's prognosis. Results: In total, 8 studies involving 13 cohorts with 3774 cases were included. Pooled results from both univariate and multivariate analyses revealed that higher AAPR was an independent prognostic factor for overall survival (HR=0.429, 95% CI: 0.361-0.509, P=0.001; HR=0.476, 95% CI: 0.421-0.538, P=0.001; respectively). Similarly, pooled multivariate results showed that higher AAPR was associated with better disease-free survival (HR=0.558, 95% CI: 0.452-0.688, P=0.001). Moreover, pooled results from both univariate and multivariate analyses revealed that higher AAPR was an independent prognostic factor for recurrence-free survival (HR=0.540, 95% CI: 0.420-0.694, P=0.001; HR=0.647, 95% CI: 0.494-0.848, P=0.002; respectively). Subgroups analysis showed that elevated AAPR still significantly correlated with better overall survival across the confounding factors. Moreover, sensitivity analysis suggested the robustness of these findings and no publication bias was detected. Conclusions: In summary, higher AAPR could be considered as a reliable prognostic factor in patients with HCC, which could be used as a routine inspection of HCC patients to individualized prognosis prediction and clinical decision making.

Risk factors behind the increase of early-onset cancer in Italian adolescents and young adults: An investigation from the Italian AYA Working group.

The incidence of early-onset cancers in adolescents and young adults (AYA) has been increasing worldwide since the 1990s. In Italy, a significant increased rate of 1.6 % per year has been reported for early-onset cancers among females between 2008 and 2016. This is mainly attributable to melanoma, thyroid, breast and endometrial cancer. The aim of our work was to describe temporal trends of the main established lifestyle risk factors (tobacco use, alcohol consumption, obesity, physical inactivity, dietary westernization and reproductive factors) over the last 20 years in the Italian AYA population. Available data on behavioural risk factors, individual and household daily life have been obtained and elaborated from PASSI, ISTAT and Eurostat reports. Lowering age of smoking initiation, an increase in alcohol drinkers among young females, and an obesity and overweight epidemic, particularly among children and adolescents as a result of physical inactivity and dietary habits, may be contributing factors behind this cancer epidemic, especially among females. In-depth investigations are needed to understand the exact role of each contributing factor, the effects of exposure to nicotine-containing products and environmental factors such as endocrine disruptors that could play a role in this phenomenon.

Functional and therapeutic significant of heat-shock protein 90 (HSP90) in reproductive cancers.

Reproductive cancers, such as ovarian, cervical, and endometrial carcinomas, have a poor prognosis in metastatic stages. Researchers are continuously seeking improved and safer methods to target cancer-related oncoproteins, addressing the limitations of current treatments, including their limited effectiveness, drug resistance, and off-target effects. Recent advancements in understanding the molecular mechanisms involved in the progress of reproductive cancers have provided valuable insights into potential targeted therapies. By engaging with oncoproteins and co-chaperones, heat-shock protein 90 (HSP90) regulates signaling networks and fixes protein folding errors in cancer cells. The potential of HSP90 inhibition as cancer-targeted treatments is underscored by the continuous discovery and testing of novel HSP90-targeted molecules for their antitumor properties in preclinical and clinical settings. Therefore, this study aims to shed light on the mechanism and recent research breakthroughs of HSP90, as well as provide an in-depth review of their therapeutic potential in reproductive cancers.

An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies.

OBJECTIVE: Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS: We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS: Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION: Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.

Quercetin (QUE) is a natural flavonoid with well-known anticancer capabilities, although its effect on viral-induced cancers is less studied. Kaposi's sarcoma (KS) is a viral cancer caused by the human herpesvirus-8, which, during its lytic phase, expresses a constitutively activated viral G protein-coupled receptor (vGPCR) able to induce oncogenic modifications that lead to tumor development. The aim of this work was to investigate the potential effect of QUE on in vitro and in vivo models of Kaposi's sarcoma, developed by transforming endothelial cells with the vGPCR of Kaposi's sarcoma-associated herpesvirus. Initially, the antiproliferative effect of QUE was determined in endothelial cells stably expressing the vGPCR (vGPCR cells), with an IC50 of 30 µM. Additionally, QUE provoked a decrease in vGPCR cell viability, interfered with the cell cycle progression, and induced apoptosis, as revealed by annexin V/PI analysis and caspase-3 activity. The presence of apoptotic bodies and disorganized actin filaments was observed by SEM and phalloidin staining. Furthermore, tumors from vGPCR cells were induced in nude mice, which were treated with QUE (50 or 100 mg/kg/d) resulting in retarded tumor progression and reduced tumor weight. Notably, neither kidney nor liver damage was observed, as indicated by biochemical parameters in serum. In conclusion, this study suggests for the first time that QUE exhibits antineoplastic activity in both in vitro and in vivo models of KS, marking a starting point for further investigations and protocols for therapeutic purpose.

Metabolic syndrome is linked to most cancers incidence.

Since many people die of either cancers or cardiovascular diseases worldwide, it is important to find the clinical pitfall that provokes cardiovascular diseases and cancer overall. Since metabolic syndrome (MetS) is largely linked to cardiovascular diseases, we have come to consider that MetS, even in its early state, may prime the occurrence of cancers overall. Indeed, the importance of MetS in causing pancreatic cancer has been proved using our large medical database. We analyzed Japanese healthcare and clinical data in 2005, who were followed up until 2020 and we examined the incidence of major cancers. At the enrollment, we examined the presence or absence of MetS judged by either Japanese criteria or NCEP/ATPIII. Of 2.7 million subjects without missing data, 102,930; 200,231; 237,420; 63,435; 76,172; and 2,422 subjects suffered lung, stomach, colon, liver and prostate cancer, respectively, and myelogenous leukemia during follow-up. MetS, defined by Japanese criteria, increased (p < 0.005 each) the incidence of cancer with a hazard ratio (HR) of 1.03-1.47 for lung, stomach, colon, liver, prostate cancers, and myelogenous leukemia. According to Japanese criteria, cancer incidence in the pre-stage MetS group was comparable to the MetS group. The results were almost identical when we defined MetS using NCEP ATP III. Taken together, we conclude that MetS is linked to majority of cancers.

Comprehensive Review of Post-treatment Imaging in Head and Neck Cancers: From expected to unexpected and beyond.

Head and neck cancer management requires multidisciplinary approach in which radical surgery with or without flap reconstructions and neck dissection, along with radiotherapy (RT)/chemoradiotherapy (CRT) serve as the key components. Neoadjuvant chemotherapy (NACT) and immunotherapy are used in selected cases based on the institutional preference. Knowledge of expected posttreatment changes on imaging is essential to differentiate it from recurrence. In addition, awareness of various posttreatment complications is imperative for their early detection on imaging. Distorted anatomy after treatment poses diagnostic challenge, hence, proper choice of imaging modality and appropriate timing of scan is pertinent for accurate posttreatment evaluation. In this article, we have provided a comprehensive review on expected imaging appearances post RT/CRT and after major types of head and neck squamous cell carcinoma (HNSCC) surgeries. In addition, we have extensively reviewed the imaging appearances of various posttreatment complications, and recurrences at the primary and lymph nodal sites. We have also delved into the patterns of recurrence in human papillomavirus (HPV) positive HNSCC in this article. Furthermore, we have provided flowcharts and discussed recommendations on the site-specific and treatment related imaging modalities to be used along with their appropriate timing, for adequate evaluation of HNSCC after treatment. We have also reviewed posttreatment reporting of imaging findings using Neck Imaging Reporting and Data Systems (NIRADS) and Hopkins criteria. In addition, we have also touched upon the role of advanced imaging techniques for posttreatment HNSCC evaluation.

The Prognostic Implications of Synchronous Cancers in Breast Cancer Patients.

OBJECTIVE: This study aims to examine the prognostic value of synchronous cancer diagnosis following an initial diagnosis of breast cancer, with a focus on site-specific survival rates and the correlation between primary breast cancer and secondary cancers. METHODS: We conducted a retrospective analysis of patients treated at Saint Nicholas Hospital in Pitesti, Romania, from January 2016 to January 2024. The inclusion criteria were a confirmed diagnosis of primary breast cancer and a secondary synchronous cancer diagnosed within two months. Data collection included demographic, clinical, and pathological characteristics, as well as treatment details and follow-up outcomes. Statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, New York, USA), employing Kaplan-Meier survival curves, Cox regression models, and other relevant statistical tests. RESULTS: Out of 73 initially identified patients, 49 met the inclusion criteria. The mean age was 59.6 years, with most patients being postmenopausal. Synchronous cancers were primarily contralateral breast cancer (44.9%) and female genital organ cancer (12.24%). Patients with synchronous bilateral breast cancer had significantly better overall survival (33 months) compared to those with other synchronous cancers (23.5 months). Multivariate analysis indicated that synchronous non-breast cancers were associated with a higher risk of death (hazard ratio (HR)=1.6, 95% CI: 1.22-2.10, p=0.003). CONCLUSION: Synchronous cancer diagnosis following an initial breast cancer diagnosis significantly impacts prognosis, with synchronous bilateral breast cancer associated with better survival outcomes compared to other synchronous cancers. These findings underscore the importance of vigilant screening and personalized treatment strategies for patients with synchronous malignancies.

Adaptive Stereotactic Body Radiation Therapy in the Management of Oligometastatic Uterine Leiomyosarcoma: A Clinical Case Report.

Safe delivery of stereotactic body radiation therapy (SBRT) to large (>5 cm) oligometastatic abdominopelvic tumors can often be challenging, especially in tumors that require a higher biologically effective dose (BED) for tumor control. Adaptive stereotactic body radiation therapy (A-SBRT) involves inter-fraction and real-time replanning while the patient is on the treatment table, potentially allowing for improved dose coverage and greater sparing of critical structures. Our case report illustrates the benefit of CT-based A-SBRT in the treatment and management of an oligometastatic uterine leiomyosarcoma patient with a rapidly enlarging pelvic recurrence. A 60-year-old female presented to the radiation oncology clinic for treatment of an enlarging, right pelvic oligometastatic leiomyosarcoma. She was prescribed 35 Gy in five fractions. Planning prioritized the sparing of nearby small bowels while maximizing coverage of the planning target volume (PTV). On treatment day, two plans were calculated, the initial plan recalculated on the current CBCT (scheduled plan) and a plan reoptimized using current contours (adapted plan), and the more appropriate one was chosen for delivery. The adapted plan was chosen for all five fractions, with the adapted plan offering better small bowel sparing in five fractions and better target coverage in four fractions, delivering a total of 34 Gy to 95% of the PTV while limiting the small bowel to a maximum point dose of 37 Gy. At approximately six months out from treatment, the patient showed continued radiographic response and resolved acute Grade 1 gastrointestinal toxicity. This case study therefore demonstrates the successful treatment of a large oligometastatic abdominopelvic tumor using CT-based A-SBRT and builds on previous experience treating abdominal cases adaptively.

Clinical glycoproteomics: methods and diseases.

Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry-based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.

Sarcomatoid Carcinoma of the Small Intestine: A Case Report.

Sarcomatoid carcinoma of the gastrointestinal tract is an extremely rare and aggressive tumor with both epithelial and mesenchymal characteristics, and it typically has a poor prognosis. We report the case of a 74-year-old male diagnosed with sarcomatoid carcinoma of the duodenum. The patient presented with gastrointestinal bleeding and was found to have a vascular tumor in the third part of the duodenum. Initial duodenal biopsies, repeat biopsies, and extensive immunohistochemical analysis confirmed a diagnosis of sarcomatoid carcinoma. Despite radical surgery and multiple lines of chemotherapy, including carboplatin and paclitaxel, the disease demonstrated aggressive progression, ultimately leading to the patient's death two years post-diagnosis. This report highlights the challenges in diagnosing and treating sarcomatoid carcinoma of the small intestine, the limited efficacy of current therapeutic options, and the need for further research to establish effective treatment protocols.

An Atypical Presentation of Diffuse Basaloid Human Papillomavirus (HPV)-Related Squamous Cell Carcinoma of the Oral Cavity in the Setting of Prior Radiation.

Basaloid squamous cell carcinoma (BSCC) is a rare subtype of squamous cell carcinoma (SCC) that can occur in the head and neck region. This particularly aggressive type of SCC has been linked to human papillomavirus (HPV) and carries a better prognosis when found in the oropharynx. We present a rare manifestation of oropharyngeal basaloid HPV-related SCC in a 75-year-old female with a history of prior radiation to the head and neck area for moderately differentiated SCC of the epiglottis. The patient presented with an erythematous rash-like mucosal lesion that extended from the oral vestibule and mucosa of the lower lip to the right buccal trigone, without any mass lesions. The case presented here is unique due to the presence of oral HPV-related BSCC in the setting of a past medical history of prior head and neck radiation. The nature of this lesion can result in late-stage diagnosis and poor patient outcomes. The uncharacteristic presentation seen in this patient emphasizes the importance of early diagnosis and management. Awareness of a variety of presentations of this aggressive cancer type is warranted due to the poor prognosis this variant carries, especially when diagnosed in advanced stages.

How enteral nutrition modes influence nasopharyngeal carcinoma survivors with late dysphagia after radiotherapy: a randomized controlled study.

BACKGROUND: Palliation to late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC) continues to be a challenge. Intermittent oro-esophageal tube feeding (IOE) is an emerging enteral nutrition mode that can address nutrition and quality of life issues related to nasogastric tube feeding (NGT). OBJECTIVES: This study aims to investigate the effect of IOE versus NGT in late dysphagia after radiotherapy for NPC. METHODS: This randomized controlled study included 82 NPC survivors with late dysphagia after radiotherapy. The subjects were randomized divided into the IOE and NGT groups (n1 = n2 = 41). Both groups received standard-of-care rehabilitation. Enteral nutrition supports were administered through IOE or NGT accordingly. This study lasted 2 weeks for each participant. The primary outcome was nutritional status including albumin, hemoglobin, total serum protein, and body mass index. The secondary outcomes were (i) the functional oral intake scale (FOIS), (ii) the penetration-aspiration scale (PAS), (iii) oral transit time (OTT), (iv) hyoid pause time (HPT), (v) pharyngeal transport time (PTT), and (vi) swallowing-quality of life (SWAL-QoL). RESULTS: Three cases quitted the study halfway and there were no significant baseline differences between the IOE (n = 40) and NGT (n = 39) groups. Both time and group effects were significant in all nutritional indicators. The time effect was significant in the FOIS levels, OTT and PTT, while the group effect was not. Either time or group effect were insignificant in the PAS levels and HPT. Both group and time effects were significant in the SWAL-QoL total scores (zGroup = 5.080, P < 0.001; zTime = 18.005, P < 0.001). The significance of time and group effects varied across different dimensions of the SWAL-QoL. CONCLUSIONS: Rehabilitation interventions can improve swallowing function among NPC survivors with late dysphagia after radiotherapy. In this population who received standard-of-care rehabilitation, IOE is more conducive to the improvement of nutritional status, and swallowing-related quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06301763.

Association Between Type 1 Diabetes Mellitus and Incident Gastrointestinal Cancer in Korean Population: A Nationwide Retrospective Cohort Study.

BACKGROUND: The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex. MATERIALS AND METHODS: This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers. RESULTS: Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age. CONCLUSIONS: The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care.

Dysregulation of lysine acetylation in the pathogenesis of digestive tract cancers and its clinical applications.

Recent advances in high-resolution mass spectrometry-based proteomics have improved our understanding of lysine acetylation in proteins, including histones and non-histone proteins. Lysine acetylation, a reversible post-translational modification, is catalyzed by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Proteins comprising evolutionarily conserved bromodomains (BRDs) recognize these acetylated lysine residues and consequently activate transcription. Lysine acetylation regulates almost all cellular processes, including transcription, cell cycle progression, and metabolic functions. Studies have reported the aberrant expression, translocation, and mutation of genes encoding lysine acetylation regulators in various cancers, including digestive tract cancers. These dysregulated lysine acetylation regulators contribute to the pathogenesis of digestive system cancers by modulating the expression and activity of cancer-related genes or pathways. Several inhibitors targeting KATs, KDACs, and BRDs are currently in preclinical trials and have demonstrated anti-cancer effects. Digestive tract cancers, including encompass esophageal, gastric, colorectal, liver, and pancreatic cancers, represent a group of heterogeneous malignancies. However, these cancers are typically diagnosed at an advanced stage owing to the lack of early symptoms and are consequently associated with poor 5-year survival rates. Thus, there is an urgent need to identify novel biomarkers for early detection, as well as to accurately predict the clinical outcomes and identify effective therapeutic targets for these malignancies. Although the role of lysine acetylation in digestive tract cancers remains unclear, further analysis could improve our understanding of its role in the pathogenesis of digestive tract cancers. This review aims to summarize the implications and pathogenic mechanisms of lysine acetylation dysregulation in digestive tract cancers, as well as its potential clinical applications.