Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with poor prognosis driven by tumor heterogeneity and therapy resistance. Mitochondrial solute carriers (SLC25 family) are crucial for metabolic and redox regulation, yet their roles in HCC remain poorly understood. Methods Transcriptome analysis integrating TCGA and GTEx datasets identified dysregulated SLC25 genes, from which prognostic members were screened by Cox and LASSO regression. Clinical validation was performed using patient tissues. Functional assays were conducted in SLC25A39 knockdown and overexpression models in vitro and in xenografts. Redox homeostasis and necroptotic signaling were evaluated by ROS/GSH/MDA assays, pharmacological inhibition, RNA-seq, and immunoblotting. Interactions between SLC25A39 and PRDX1 were verified by mass spectrometry, co-immunoprecipitation, and immunofluorescence, with PRDX1 rescue experiments assessing functional relevance. Results SLC25A39 was markedly upregulated in HCC tissues and correlated with poor overall survival. Knockdown of SLC25A39 suppressed cell proliferation, migration, invasion, and tumor growth, while overexpression enhanced malignant behaviors. Mechanistically, SLC25A39 deficiency disrupted mitochondrial redox homeostasis, inducing ROS accumulation, GSH depletion, MDA elevation, and activation of RIPK1/RIPK3/p-MLKL-mediated necroptosis. PRDX1 was identified as a direct binding partner of SLC25A39. Importantly, PRDX1 overexpression alleviated oxidative stress, suppressed necroptotic signaling, and partially restored proliferative and invasive phenotypes of SLC25A39-deficient cells. Conclusion This study identifies SLC25A39 as a novel oncogenic driver in HCC. By stabilizing PRDX1 and sustaining mitochondrial redox balance, SLC25A39 promotes tumor progression while preventing necroptotic cell death. Targeting the interplay between SLC25A39, PRDX1, and necroptotic signaling may provide new therapeutic opportunities for HCC.

Background: Gastric cancer (GC) is one of the most prevalent malignant diseases worldwide. Abnormal metabolic reprogramming, particularly cholesterol metabolism, influences tumor development and treatment outcomes. This study investigates the predictive and functional significance of cholesterol metabolism-related genes in gastric cancer patients. Methods: Clinical and gene expression data related to cholesterol metabolism in gastric cancer were analyzed using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A predictive signature was developed and validated using LASSO, Cox regression, and the GSE26889 cohort, followed by evaluation with Kaplan-Meier analysis. A nomogram was constructed by integrating the signature with clinical factors and ssGSEA for immunological analysis. The role of NPC2 was investigated using western blot, qPCR, and cellular assays. Results: We conducted a bioinformatics analysis of 50 genes associated with cholesterol metabolism in gastric cancer. Using the GEO and TCGA datasets, we identified 28 genes with differential expression in gastric cancer patients. Subsequent COX univariate and LASSO regression analyses of these 28 DEGs identified five genes (APOA1, APOC3, NPC2, CD36, and ABCA1) as independent prognostic risk factors. We then constructed a risk model for cholesterol metabolism genes, revealing that survival was worse in the high-risk group compared to the low-risk group, with more severe case staging outcomes. We conducted a comparative analysis of immune cells between the high-risk and low-risk groups, revealing distinct variations in immune cell type expression. We then developed a model using a correlation nomogram to illustrate these conclusions. We further examined the biological characteristics of NPC2. Immunohistochemistry and qPCR results showed that NPC2 exhibited significant protein and mRNA expression in gastric cancer tissues. We used siRNA technology to suppress NPC2, resulting in reduced viability, proliferation, and invasion capacity of gastric cancer cells, as determined by CCK-8, colony formation, wound healing, and Transwell assays. Conclusion: A risk signature comprising five cholesterol metabolism-related genes was constructed using bioinformatics to estimate outcomes and therapeutic responses in gastric cancer patients. The results suggest that NPC2 may serve as a novel biomarker for gastric cancer patients.

Background: After glucagon and insulin, amylin is the third most significant and active islet hormone. Amylin and insulin act synergistically to suppress postprandial blood glucose levels. Research has shown that insulin plays a vital role in the growth and progression of cancer; however, the relationship between amylin and gastric cancer (GC) is unclear.Methods This study used a combination of in vitro and in vivo experiments to investigate the role of amylin in the progression of GC. The expression of amylin in GC and its clinical correlation were evaluated using 38 pairs of GC and healthy human clinical samples. In vitro studies, human GC cell lines were treated with amylin to evaluate the effects of amylin on the proliferation, apoptosis and migration of GC cells. In in vivo studies, xenograft mouse models were established by subcutaneous injection of GC cells into nude mice, followed by treatment with amylin to assess tumor growth. Finally, Next-Generation Sequencing Technology (RNA-seq) was used to explore the potential mechanism of amylin on GC.Results We found that amylin expression was reduced in GC compared to adjacent normal gastric tissues and that elevated amylin expression was negatively correlated with adverse pathological factors (p < 0.05). Additionally, we demonstrated that amylin impeded the growth, invasion, migration, and colony formation of GC cells and suppressed the epithelial-to-mesenchymal transformation of these cells (p < 0.05). Tumour xenograft model experiments confirmed the tumour-suppressive effect of amylin in subcutaneous tumours in nude mice (p < 0.05). Transcriptome sequencing (RNA-seq) revealed that amylin significantly down-regulated CCN1 gene expression in GC cells (p < 0.001). Further intervention targeting CCN1 verified its significance as a target of amylin’s anti-carcinogenic function in GC. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that amylin exerted its oncogenic effects by inhibiting the PI3K/Akt signalling pathway (p < 0.05).Conclusions Our findings demonstrate that amylin plays a crucial role in suppressing gastric cancer progression by targeting CCN1 and inhibiting the PI3K/Akt signalling pathway. These results suggest that amylin could serve as a potential therapeutic agent for GC treatment.

OBJECTIVE:This study aimed to investigate the expression levels of SIRT1 protein in gastric (GC), colon (CC), and rectal cancer (RC) tissues and patient plasma, analyze its correlation with clinicopathological features and prognosis, and preliminarily explore its relationship with the tumor immune microenvironment. METHODS:Plasma samples were collected from 198 gastrointestinal cancer patients (66 each of GC, CC, and RC) and 66 healthy volunteers. Additionally, cancerous and adjacent normal tissues were obtained from 45 of these patients (15 pairs for each cancer type). SIRT1 concentration in plasma was detected using Enzyme-Linked Immunosorbent Assay (ELISA). SIRT1 protein expression in tissues was examined using Immunohistochemistry (IHC) and Western Blotting. Bioinformatic analysis was performed using TCGA and GEPIA databases. The correlation between SIRT1 and immune cell infiltration was analyzed via the TIMER database. Statistical analyses were conducted using SPSS software. RESULTS:Plasma SIRT1 concentration was significantly higher in the GC group compared to healthy controls (p = 0.045), while it was significantly lower in the CC and RC groups (p = 0.007 and p = 0.009, respectively). In tissues, SIRT1 expression was up-regulated in GC but down-regulated in colorectal cancer (CC and RC) tissues (p < 0.05). SIRT1 expression levels were significantly correlated with clinicopathological features including tumor differentiation degree, depth of invasion, TNM stage, distant metastasis (in colorectal cancer), and lymph node metastasis (in RC) (p < 0.05). Survival analysis revealed that high SIRT1 expression was associated with poorer overall survival (OS) in GC patients (p = 0.032), while low expression was associated with poorer OS in RC patients (p = 0.027). Plasma SIRT1 levels showed significant correlations with various tumor markers (e.g., CEA, CA199, CA125, CA724). Furthermore, SIRT1 expression was positively correlated with the infiltration levels of immune cells such as CD4+ T cells, CD8+ T cells, macrophages, and neutrophils. CONCLUSION:SIRT1 expression in gastrointestinal tumors is tissue-specific (upregulated in GC, downregulated in colorectal cancer). Its expression level is closely associated with malignant progression and patient prognosis, and it may be involved in the modulation of the tumor immune microenvironment. SIRT1 shows promise as a potential diagnostic biomarker and therapeutic target for gastrointestinal cancers.

Emerging evidence underscores the critical, yet frequently underrecognized, role of the nervous system in the development and progression of gastric cancer (GC), primarily mediated through complex neuro-tumoral interactions and modulation of immune responses. GC cells actively invade neural structures, inducing aberrant nerve growth, while, in parallel, neural components infiltrate the tumor microenvironment, collectively promoting tumor proliferation, dissemination, and resistance to therapy. These bidirectional processes are regulated by diverse neurotransmitter systems-including monoaminergic, cholinergic, amino acid-based, peptidergic, and purinergic pathways-which are aberrantly produced by both neurons and malignant cells. Beyond their canonical function in neural signaling, these neuromediators exert diverse effects on tumor biology, coordinating multiple facets of GC progression, including invasion, metastasis, and cellular expansion. This review synthesizes current advances and outlines future directions in elucidating the mechanistic contributions of neurotransmitters to GC pathophysiology.

OBJECTIVE:To explore the biological function of RELA proto-oncogene, NF-kB subunit (RELA) in hepatocellular carcinoma (HCC) progression, and its potential regulatory effects on the regulators of m6A modification.METHODS AND MATERIALS:GEPIA, UALCAN and Human Protein Atlas databases were applied to analyze the expression characteristics of RELA in HCC tissues and non-cancer liver tissues, and its relationship with clinicopathologic indicators and prognosis. Quantitative real-time PCR (qRT-PCR) was used to examine the expression level of RELA mRNA in HCC cells. Cell counting kit-8 (CCK-8) assay, EdU assay and flow cytometry were used to examine cell growth and apoptosis. PROMO database was applied to predict the binding sequence between RELA and methyltransferase like protein 3 (METTL3) promoter region, and this prediction was verified by dual luciferase reporter gene experiment and chromatin immunoprecipitation assay. The effect of RELA on METTL3 expression was examined by Western blot and qRT-PCT, and the regulatory effects of RELA on the other m6A regulators were evaluated by qRT-PCR.RESULTS:RELA was highly expressed in HCC tissues and cell lines, and was closely associated with adverse clinicopathologic indicators and poor prognosis of patients. Overexpression of RELA promoted the growth of HCC cells and inhibited apoptosis; Knocking down RELA had the opposite effects. Overexpression of RELA promoted METTL3 transcription. Knockdown or overexpression of METTL3 reversed the effects of overexpression or knockdown of RELA on HCC cell growth and apoptosis, respectively. RELA also promoted the expression of a series of m6A regulators at mRNA expression level in HCC cell lines.CONCLUSION:RELA promotes the transcription of METTL3 by binding to METTL3 promoter region, thus promoting the malignancy of HCC cells. This study suggests NF-κB signaling contributes the dysregulation of m6A modification in HCC tumorigenesis.

The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.

Innate immune cells in the colorectal cancer microenvironment mainly include macrophages, neutrophils, natural killer cells, dendritic cells and bone marrow-derived suppressor cells. They play a pivotal role in tumor initiation and progression through the secretion of diverse cytokines, chemokines, and other factors that govern these processes. Colorectal cancer is a common malignancy of the gastrointestinal tract, and understanding the role of innate immune cells in the microenvironment of CRC may help to improve therapeutic approaches to CRC and increase the good prognosis. In this review, we comprehensively explore the pivotal role of innate immune cells in the initiation and progression of colorectal cancer (CRC), alongside an extensive evaluation of the current landscape of innate immune cell-based immunotherapies, thereby offering valuable insights for future research strategies and clinical trials.

DBF4 zinc finger (DBF4) is a critical component involved in DNA replication and cell proliferation. It acts as a positive regulator of the cell division cycle 7 kinase. In this study, our investigation encompassed the impact of DBF4 on hepatocellular carcinoma (HCC) progression and delved into the potential mechanisms. We utilized open-access databases like TCGA and GEO to analyze the association between DBF4 and 33 different tumor types. We also conducted immunohistochemistry experiments to validate the expression of DBF4 in HCC, STAD, COAD, READ, PAAD, and LGG. Furthermore, we employed lentiviral transduction to knockdown DBF4 in HLF and SMMC cells, as well as to overexpress DBF4 in Huh7 cells. Subsequently, we evaluated the impact of DBF4 on proliferation, migration, and invasion of hepatocellular carcinoma cells. RNA sequencing and KEGG pathway enrichment analysis were also conducted to identify potential pathways, which were further validated through WB experiments. Finally, pathway inhibitor was utilized in rescue experiments to confirm whether DBF4 exerts its effects on tumor cells via the implicated pathway. Our findings revealed that DBF4 exhibited significant expression levels in nearly all examined tumors, which were further substantiated by the results of immunohistochemistry analysis. High DBF4 expression was correlated with poor overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), disease-free interval (DFI), relapse-free interval (RFI) in majority of tumor types, particularly in patients with HCC. In vitro experiments demonstrated that inhibition of DBF4 impaired the proliferative, migratory, and invasive abilities of HCC cells, whereas overexpression of DBF4 promoted these phenotypes. Sequencing results indicated that DBF4 may induce these changes through the ERBB signaling pathway. Further experimental validation revealed that DBF4 activates the ERBB signaling pathway, leading to alterations in the JNK/STAT, MAPK, and PI3K/AKT signaling pathways, thereby impacting the proliferative, migratory, and invasive abilities of tumor cells. Lastly, treatment of Huh7 cells overexpressing DBF4 with the ERBB2 inhibitor dacomitinib demonstrated the ability of ERBB2 inhibition to reverse the promoting effect of DBF4 overexpression on the proliferative, migratory, and invasive abilities of HCC cells. DBF4 plays a pivotal oncogenic role in HCC by promoting the ERBB signaling pathway and activating its downstream PI3K/AKT, JNK/STAT3, and MAPK signaling pathways. DBF4 may serve as a prognostic biomarker for patients with HCC.

ATP citrate lyase (ACLY) and acyl-CoA short-chain synthetases 2 (ACSS2) are key enzymes in lipid metabolism. We explored the role of ACLY in gastric cancer (GC) and the effect of ACLY and ACSS2 compensation on GC growth. We used immunohistochemistry to verify the expression level of ACLY in GC, shRNA to stably knock down the expression level of ACLY in GC cells. The expression levels of lipid metabolizing enzymes were verified by qPCR and WB, and targeted lipidomics and quantification of lipid metabolism-related indicators helped us to understand the changes in lipid metabolism. Finally, subcutaneous graft tumors validate our findings from in vitro experiments. ACLY is upregulated in GC tissues, downregulation of ACLY reduced lipid accumulation and inhibited GC proliferation, migration, and invasion in vitro. ACSS2 maintains cell growth by compensatory elevation to maintain fatty acid synthesis activity in ACLY-depleted GC cells. Inhibition of ACSS2 enhanced the inhibitory effect of downregulation of ACLY on the growth of transplanted tumors in nude mice. Downregulation of ACLY inhibited GC cell growth in vitro and in vivo. ACSS2 was compensated to increase to maintain cell growth in ACLY-depleted GC cells.

Objective: The impact of sarcopenia on the efficacy of immune checkpoint inhibitors (ICI) in gastroin-testinal cancer (GIC) patients remains uncertain in clinical practice. Hence, this study aims to investigate the potential correlation between sarcopenia and the clinical outcomes of GIC patients treated with ICIs.Methods: To gather pertinent studies, a systematic literature search was implemented across multiple databases, including PubMed, Embase, the Cochrane Library, and Google Scholar. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), measured with the hazard ratio (HR). And the secondary outcomes, including disease control rate (DCR), overall response rate (ORR), and adverse events (AE), were evaluated with the odd ratio (OR). Results: A total of 13 articles involving 1294 patients were collected for this analysis. The pooled results revealed that GIC patients with sarcopenia had significantly poorer OS (HR = 1.697, 95% CI = 1.367-2.106, p < 0.001) and PFS (HR: 1.551, 95% CI: 1.312-1.833, p < 0.001), and lower ORR (OR = 0.594, 95% CI = 0.388-0.909, p = 0.016) and DCR (OR: 0.553, 95% CI: 0.360-0.850, p = 0.007) compared to those without sarcopenia. However, sarcopenia did not increase the incidence of treatment-related adverse events compared with non-sarcopenia (OR = 1.377, 95% CI = 0.693-2.737, p = 0.361). According to subgroup analysis, the association between sarcopenia and the therapeutic effect of ICI on patients with primary liver cancer or gastric cancer was consistent with the above findings.Conclusion: Sarcopenia is significantly correlated with poorer treatment response and worse long-term efficacy in GIC patients treated with ICIs. Moreover, sarcopenia does not increase the incidence of adverse events.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

ObjectiveTo understand the relationship between steroid hormones synthesized by the gonads and colorectal cancer as well as its tumor microenvironment, in the expectation of providing new ideas in order to detect and treat colorectal cancer.MethodsThrough reviewing the relevant literature at home and abroad, we summarized that androgens promote the growth of colorectal cancer, and estrogens and progesterone help prevent bowel cancer from developing; these three hormones also have a relevant role in the cellular and other non-cellular components of the tumor microenvironment of colorectal cancer.ConclusionThe current literature suggests that androgens, estrogens, and progesterone are valuable in diagnosing and treating colorectal cancer, and that androgens promote the growth of colorectal cancer whereas estrogens and progesterone inhibit colorectal cancer, and that, in addition, the receptors associated with them are implicated in the modulation of a variety of cellular components of the microenvironment of colorectal cancer.

Hepatocellular carcinoma (HCC) is a widespread and impactful cancer which has pertinent implications worldwide. Although most cases of HCC are typically diagnosed in individuals aged ≥60 years, there has been a notable rise in the occurrence of HCC among younger patients. However, there is a scarcity of precise prognostic models available for predicting outcomes in these younger patients. A retrospective analysis was conducted to investigate early-onset hepatocellular carcinoma (EO-LIHC) using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2018. The analysis included 1392 patients from the SEER database and our hospital. Among them, 1287 patients from the SEER database were assigned to the training cohort (n = 899) and validation cohort 1 (n = 388), while 105 patients from our hospital were assigned to validation cohort 2. A Cox regression analysis showed that age, sex, AFP, grade, stage, tumor size, surgery, and chemotherapy were independent risk factors. The nomogram developed in this study demonstrated its discriminatory ability to predict the 1-, 3-, and 5-year overall survival (OS) rates in EO-LIHC patients based on individual characteristics. Additionally, a web-based OS prediction model specifically tailored for EO-LIHC patients was created and validated. Overall, these advancements contribute to improved decision-making and personalized care for individuals with EO-LIHC.

Abstract Background Systemic inflammation is crucial for the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is considered to be a better indicator of systemic inflammation than current biomarkers. However, the prognostic value of the ALI in gastrointestinal neoplasms remains unclear. We performed the first meta-analysis to explore the association between ALI and gastrointestinal oncologic outcomes to help physicians better evaluate the prognosis of those patients. Methods Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 29, 2022. Clinical outcomes were overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). Results A total of 18 articles with 6898 patients were included in this meta-analysis. The pooled results demonstrated that a low ALI was correlated with poor OS (HR = 1.914, 95% CI: 1.514–2.419, P < 0.001), DFS (HR = 1.631, 95% CI: 1.197–2.224, P = 0.002), and PFS (HR = 1.679, 95% CI: 1.073–2.628, P = 0.023) of patients with gastrointestinal cancers. Subgroup analysis revealed that a low ALI was associated with shorter OS (HR = 2.279, 95% CI: 1.769–2.935, P < 0.001) and DFS (HR = 1.631, 95% CI: 1.197–2.224, P = 0.002), and PFS (HR = 1.911, 95% CI: 1.517–2.408, P = 0.002) of patients with colorectal cancer. However, the ALI was not related to CSS in the patients with gastrointestinal malignancy (HR = 1.121, 95% CI: 0.694–1.812, P = 0.640). Sensitivity analysis supported the stability and dependability of the above results. Conclusion The pre-treatment ALI was a useful predictor of prognosis in patients with gastrointestinal cancers.

Objective Intrahepatic cholangiocarcinoma (ICC) is a silent liver malignancy with an increasing incidence. Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with ICC remains elusive. This study aimed to elucidate fungal differences in patients with ICC compared to healthy controls. Methods The 40 fecal samples from 23 ICC patients and 17 healthy controls were collected and analyzed using ITS2 rDNA sequencing. Obtaining the OTUs and combining effective grouping, we carried out the biodiversity and composition of the fungi, as well as FUNGuild functional annotation. Results Our results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Candida and C. albicans, and significant depletion of the beneficial fungus Saccharomyces cerevisiae in ICC patients compared with healthy controls. Alpha-diversity analysis demonstrated that patients with ICC showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the two groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the ICC patients with TNM stage III-IV than those with stage I-II. The FUNGuild functional classification predicted that pathotrophs were the most abundant taxon in the ICC group, well above their abundance in healthy controls. Conclusion This study indicates that dysbiosis of the fecal mycobiome might be involved in ICC development. Further research into gut fungi may contribute to new therapeutic options for ICC patients.

OBJECTIVE:We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS:Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). RESULTS:A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.951, P < 0.001) and PFS (HR: 1.632, P < 0.001), lower ORR (OR: 0.484, P < 0.001) and DCR (OR: 0.494, P = 0.027), and higher HPD (OR: 8.190, P < 0.001). The patients with high AFP levels had shorter OS (HR: 1.689, P < 0.001) and PFS (HR: 1.380, P < 0.001), and lower DCR (OR: 0.440, P < 0.001) than those with low AFP levels, however, there was no difference in ORR (OR: 0.963, P = 0.933). We also found that early AFP response was correlated with better OS (HR: 0.422, P < 0.001) and PFS (HR: 0.385, P < 0.001), higher ORR (OR: 7.297, P < 0.001) and DCR (OR: 13.360, P < 0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR: 2.440, P = 0.009) and PFS (HR: 1.373, P = 0.022), lower ORR (OR: 0.618, P = 0.032) and DCR (OR: 0.672, P = 0.049) than those with an ALBI grade 1. CONCLUSION:The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.

OBJECTIVE:Immune checkpoint inhibitors (ICI) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to explore the impact of antibiotic use on outcomes in ICI-treated EGC patients. METHODS:Patients with advanced EGC treated with ICIs at our center were identified between 2017 and 2021. The impact of antibiotic use on overall survival (OS) and progression-free survival (PFS) was assessed by a log-rank test. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 17, 2022. Clinical outcomes were OS, PFS, and disease control rate (DCR). RESULTS:In our cohort, 85 EGC patients were recruited. The results showed that antibiotic use significantly shortens OS (HR: 1.91, 95% CI: 1.11-3.28, P = 0.020) and PFS (HR: 2.13, 95% CI: 1.21-3.74, P = 0.009) and reduces DCR (OR: 0.27, 95% CI: 0.10-0.720, P = 0.013) in EGC patients treated with ICIs. The meta-analysis results revealed that antibiotic use was significantly associated with worse OS (HR = 2.454, 95% CI: 1.608-3.748, P < 0.001), PFS (HR = 2.539, 95% CI: 1.455-4.432, P = 0.001), and lower DCR (OR = 0.246, 95% CI: 0.105-0.577, P = 0.001). No publication bias existed, and sensitivity analysis confirmed stable results. CONCLUSION:In patients with advanced EGC undergoing ICI, the use of antibiotics, such as cephalosporins, was associated with inferior survival rates.

BACKGROUND:The advent of immune checkpoint inhibitors (ICIs) has altered the outlook for cancer treatment. The estimation of predictive biomarkers could contribute to maximizing the benefits from ICIs treatment. Here, we explored the association between HYDIN mutations (HYDIN-MUT) in melanoma and ICIs efficacy.METHODS:Clinical data and sequencing data from published studies were utilized to assess the association between HYDIN-MUT and the efficacy of ICIs treatment in melanoma patients.RESULTS:Compared to other tumor types, HYDIN (36.14%) has the highest mutation rate in melanoma patients. In the anti-PD-1 treated cohort (n = 254), the HYDIN-MUT patients had a longer OS after ICIs treatment than the HYDIN wild-type (HYDIN-WT) patients (HR = 0.590 [95% CI, 0.410-0.847], P = 0.004); the objective response rate (ORR) and durable clinical benefit (DCB) were increased in patients with HYDIN-MUT (ORR = 46.25, DCB = 56.00%) compared to patients with HYDIN-WT (ORR = 30.99%, DCB = 42.76%) (ORR: P = 0.019; DCB: P = 0.060). In the anti-CTLA4 treated cohort (n = 174), HYDIN-MUT patients achieved significantly longer OS than HYDIN-WT patients (HR = 0.549 [95% CI, 0.366-0.823], P = 0.003); the proportion of ORR and DCB in HYDIN-MUT patients was significantly higher than that in HYDIN-WT patients (ORR 40.54% vs. 14.42%, P = 0.031; DCB 45.76% vs. 22.22%, P = 0.002). Further gene set enrichment analysis demonstrated that DNA repair and anti-tumor immunity were significantly enhanced in HYDIN-MUT patients.CONCLUSIONS:HYDIN mutations are a potential predictive biomarker of ICIs efficacy in melanoma patients.

The maintenance of intestinal renewal and repair mainly depends on intestinal stem cells (ISCs), which can also contribute to the growth of intestinal tumours. Hormones, which are vital signalling agents in the body, have various effects on the growth and replacement of intestinal stem cells. This review summarises recent progress in the identification of hormones associated with intestinal stem cells. Several hormones, including thyroid hormone, glucagon-like peptide-2, androgens, insulin, leptin, growth hormone, corticotropin-releasing hormone and progastrin, promote the development of intestinal stem cells. However, somatostatin and melatonin are two hormones that prevent the proliferation of intestinal stem cells. Therefore, new therapeutic targets for the diagnosis and treatment of intestinal illnesses can be identified by examining the impact of hormones on intestinal stem cells.

ObjectiveIn this investigation, we focused on the geriatric nutritional risk index (GNRI), a comprehensive metric that takes into account the patient’s ideal weight, actual weight, and serum albumin levels to measure malnutrition. Our primary objective was to examine the predictive value of GNRI-defined malnutrition in determining the response to immunotherapy among cancer patients.MethodsRelevant articles for this study were systematically searched in PubMed, the Cochrane Library, EMBASE, and Google Scholar up to July 2023. Our analysis evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) as clinical outcomes.ResultsThis analysis comprised a total of eleven articles encompassing 1,417 patients. The pooled results revealed that cancer patients with low GNRI levels exhibited shorter OS (HR: 2.64, 95% CI: 2.08–3.36, p < 0.001) and PFS (HR: 1.87, 95% CI: 1.46–2.41, p < 0.001), and lower ORR (OR: 0.46, 95% CI: 0.33–0.65, p < 0.001) and DCR (OR: 0.42, 95% CI: 0.29–0.61, p < 0.001). Sensitivity analyses confirmed that the above results were stable. Egger’s and Begg’s tests revealed that there was no publication bias in the above results.ConclusionOur results imply that the GNRI is a useful predictor of immunotherapy response in cancer patients.