Multiple Cancer Types Research Articles

68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer

68Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer

Pan-cancer Analysis of Homologous Recombination Deficiency in Cell Lines.

Homologous Recombination Deficiency (HRD) drives genomic instability in multiple cancer types and renders tumors vulnerable to certain DNA damaging agents such as PARP inhibitors. Thus, HRD is emerging as an attractive biomarker in oncology. A variety of in silico methods are available for predicting HRD; however, few of these methods have been applied to cell lines in a comprehensive manner. Here we utilized two of these methods, "CHORD" and "HRDsum" scores, to predict HRD for 1,332 cancer cell lines and 84 non-cancerous cell lines. Cell lines with biallelic mutations in BRCA1 or BRCA2, which encode key components of the homologous recombination pathway, showed the strongest HRD predictions, validating the two methods in cell lines. A small subset of BRCA1/2-wildtype cell lines were also classified as HRD, several of which showed evidence of epigenetic BRCA1 silencing. Similar to HRD in patient samples, HRD in cell lines was associated with p53 loss, was mutually exclusive with microsatellite instability and occurred most frequently in breast and ovarian cancer types. In addition to validating previously identified associations with HRD, we leveraged cell line-specific datasets to gain new insights into HRD and its relation to various genetic dependency and drug sensitivity profiles. We found that in cell lines, HRD was associated with sensitivity to PARP inhibition in breast cancer, but not at a pan-cancer level. By generating large-scale, pan-cancer datasets on HRD predictions in cell lines, we aim to facilitate efforts to improve our understanding of HRD and its utility as a biomarker.

Landscape of subsequent therapies in perioperative immunotherapy trials across multiple cancer types

Landscape of subsequent therapies in perioperative immunotherapy trials across multiple cancer types

Single cell atlas reveals multilayered metabolic heterogeneity across tumour types

Metabolic reprogramming plays a pivotal role in cancer progression, contributing to substantial intratumour heterogeneity and influencing tumour behaviour. However, a systematic characterization of metabolic heterogeneity across multiple cancer types at the single-cell level remains limited. We integrated 296 tumour and normal samples spanning six common cancer types to construct a single-cell compendium of metabolic gene expression profiles and identify cell type-specific metabolic properties and reprogramming patterns. A computational approach based on non-negative matrix factorization (NMF) was utilised to identify metabolic meta-programs (MMPs) showing intratumour heterogeneity. In-vitro cell experiments were conducted to confirm the associations between MMPs and chemotherapy resistance, as well as the function of key metabolic regulators. Survival analyses were performed to assess clinical relevance of cellular metabolic properties. Our analysis revealed shared glycolysis upregulation and divergent regulation of citric acid cycle across different cell types. In malignant cells, we identified a colorectal cancer-specific MMP associated with resistance to the cuproptosis inducer elesclomol, validated through in-vitro cell experiments. Furthermore, our findings enabled the stratification of patients into distinct prognostic subtypes based on metabolic properties of specific cell types, such as myeloid cells. This study presents a nuanced understanding of multilayered metabolic heterogeneity, offering valuable insights into potential personalized therapies targeting tumour metabolism. National Key Research and Development Program of China (2021YFA1300601). National Natural Science Foundation of China (key grants 82030081 and 81874235). The Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). The Lam Chung Nin Foundation for Systems Biomedicine.

Exploring the Role of Cuprotosis-Associated Genes in Cancer Progression and Therapy Resistance: A Comprehensive Analysis across Multiple Cancer Types

This review presents a comprehensive overview of the role of cuprotosis-associated genes in various cancer types, highlighting their significance in tumor progression and therapy resistance. In breast cancer and colorectal cancer (CRC), dysregulation of genes involved in mitochondrial function and copper metabolism, such as FDX1, LIAS, LIPT1, DLD, DLAT, and PDHA1/PDHB, promotes metabolic reprogramming and enhances cancer cell survival. Ovarian cancer exhibits unique dysregulations in genes like ATP7B, CCS, and COMMD1, influencing copper metabolism and redox signaling pathways, thereby contributing to chemoresistance and tumor growth. Head and neck cancer involves upregulation of MT1X, ATP7A, and CCS, potentially aiding cancer cell survival under oxidative stress conditions. Lung cancer is characterized by distinct dysregulation of genes like SLC31A1, ATOX1, and COMMD1, modulating copper homeostasis and redox signaling to support tumor proliferation. Liver cancer and kidney cancer each present unique sets of dysregulated cuprotosis-associated genes, such as SLC39A4, SCO2, and ATP7A, suggesting novel therapeutic targets specific to these cancer types. Pathway analysis reveals enrichment in mineral absorption pathways, emphasizing the importance of these genes in maintaining cellular mineral homeostasis. Understanding the intricate interplay between cuprotosis-associated genes and cancer biology offers insights into potential therapeutic strategies targeting copper metabolism for improved treatment outcomes across various cancer types.

Perceptions of Multicancer Detection Tests Among Primary Care Physicians and Laypersons: A Qualitative Study.

Multicancer detection tests (MCDs) are blood-based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs. We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi-structured guide containing open-ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified. Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow-ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result. There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools.

Clinical value of comprehensive genomic profiling on clinical trial enrollment for patients with advanced solid tumors.

The use of biomarker testing to inform treatment decisions has emerged as a standard of care in multiple cancer types. However, the rates of patients with genomic testing results in hand to inform treatment decision-making remain variable. Here, we studied the impact of comprehensive genomic profiling (CGP) on clinical trial enrollment rates in patients with advanced-stage non-small cell lung, colorectal, breast, and prostate cancer using a real-world clinicogenomic database. On average, clinical trial enrollment in the therapy line immediately after CGP report receipt was 5.4%, which represents a 3.0 percentage point increase compared to therapy lines preceding CGP report receipt, supporting a meaningful association between CGP report availability and increased clinical trial enrollment.

Elraglusib induces cytotoxicity via direct microtubule destabilization independently of GSK3 inhibition.

Elraglusib (9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3) with pre-clinical studies demonstrating broad activity against many tumour types. Promising early-phase clinical trial data led to FDA orphan drug status, and a randomized phase 2 study in combination with cytotoxic chemotherapy in pancreatic cancer has recently completed its recruitment. Similarly, single-agent responses in adult T-cell leukaemia/lymphoma and melanoma, and combination treatment data in several other tumour types have been encouraging. The elraglusib mechanism of action is unknown, but it is unlikely to act through GSK3 inhibition because cytotoxicity is observed below the IC50 for GSK3 and other small molecule GSK3 inhibitors do not produce cytotoxic effects, at least in lymphoma cells. We show here that elraglusib perturbs chromosomal alignment to cause a mitotic arrest in multiple tumour lines. This arrest is caused by direct microtubule depolymerization, which prevents the attachment of kinetochores to microtubules. At clinically relevant doses, these mitotically arrested cells eventually undergo mitotic slippage, leading to gross chromosome missegregation, DNA damage and apoptosis. These effects explain the cytotoxicity of elraglusib because temporarily pausing cell cycle progression with the CDK4/6 inhibitor palbociclib abolishes any drug-induced genotoxicity and apoptosis. In summary, elraglusib acts as a direct microtubule destabilizer both in vitro and across multiple cancer types, resulting in mitotic arrest, DNA damage and apoptosis. These effects likely account for its broad pan-cancer activity, which does not rely upon GSK3 inhibition as they are not replicated by other GSK3 inhibitors.

Reduced intestinal-to-diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma.

Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment-naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25%vs. 4%, p<0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal-to-diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor-kappa B (NF-κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal-to-diffuse conversion and reprogramming to an immuno-active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy.

The present and future of the Cancer Dependency Map.

Despite tremendous progress in the past decade, the complex and heterogeneous nature of cancer complicates efforts to identify new therapies and therapeutic combinations that achieve durable responses in most patients. Further advances in cancer therapy will rely, in part, on the development of targeted therapeutics matched with the genetic and molecular characteristics of cancer. The Cancer Dependency Map (DepMap) is a large-scale data repository and research platform, aiming to systematically reveal the landscape of cancer vulnerabilities in thousands of genetically and molecularly annotated cancer models. DepMap is used routinely by cancer researchers and translational scientists and has facilitated the identification of several novel and selective therapeutic strategies for multiple cancer types that are being tested in the clinic. However, it is also clear that the current version of DepMap is not yet comprehensive. In this Perspective, we review (1) the impact and current uses of DepMap, (2) the opportunities to enhance DepMap to overcome its current limitations, and (3) the ongoing efforts to further improve and expand DepMap.

The Journey of Antibody-Drug Conjugates: Lessons Learned from 40 Years of Development.

Antibody-drug conjugates (ADC) represent one of the most rapidly expanding treatment modalities in oncology, with 11 ADCs approved by the FDA and more than 210 currently being tested in clinical trials. Spanning over 40 years, ADC clinical development has enhanced our understanding of the multifaceted mechanisms of action for this class of therapeutics. In this article, we discuss key insights into the toxicity, efficacy, stability, distribution, and fate of ADCs. Furthermore, we highlight ongoing challenges related to their clinical optimization, the development of rational sequencing strategies, and the identification of predictive biomarkers. Significance: The development and utilization of ADCs have allowed for relevant improvements in the prognosis of multiple cancer types. Concomitantly, the rise of ADCs in oncology has produced several challenges, including the prediction of their activity, their utilization in sequence, and minimization of their side effects, that still too often resemble those of the cytotoxic molecule that they carry. In this review, we retrace 40 years of development in the field of ADCs and delve deep into the mechanisms of action of these complex therapeutics and reasons behind the many achievements and failures observed in the field to date.

An Overview of the Cancer Targeting Attributes of the Elastin Like Polypeptide Nano‐Carriers: Discerning Active and Passive Modes

AbstractSince the 1940s, generalized cytotoxic therapy has been a valuable tool in cancer treatment. Over the years, there's been a significant increase in developing potential cytotoxic drugs. However, little progress has been made in enhancing patients' quality of life. The therapeutic index is limited due to the drug's poor solubility and lack of selectivity. Various carriers have been explored for drug delivery to enhance efficacy. Yet, there's a gap for a versatile delivery system that can adjust to specific drug and application requirements. Here, a multifaceted drug delivery platform based on a genetically engineered nature‐inspired polymer, elastin‐like polypeptide (ELP) is introduced. This technology enables the customization of the polymeric vehicle's physicochemical characteristics to suit the needs of a specific drug and application. The review highlights ELP's advantages in cancer targeting, such as site‐specificity, controlled release, biocompatibility, and extended plasma circulation. For the first time, ELP‐based drug delivery into passive and active targeting for better comprehension of its adaptability is classified. Moreover, numerous opportunities for loading different types of drugs onto the polymer are outlined. Finally, the polymer's efficacy in delivery across multiple cancer types, underscoring the wide spectrum of ELP‐based cancer drug delivery is precisely described.

Chromatin interaction maps identify oncogenic targets of enhancer duplications in cancer.

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer-promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1 In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

Synthesis, computational analysis, and anti-proliferative evaluation of novel bithienylbenzamidine derivatives: Towards cytostatic cancer therapeutics

Our research unveils the synthesis and characterization of four novel monocationic 2,5-diarylbithiophene derivatives 4a-d, prepared through Suzuki cross-coupling reactions and subsequent amidine formation. Density Functional Theory (DFT) calculations provide unprecedented insights into the electronic properties and structure-activity relationships of these compounds. In vitro screening against the NCI-60 cancer cell panel demonstrates remarkable anti-proliferative activities. Compound 4c emerges as a standout candidate, exhibiting potent growth inhibition across multiple cancer types, with GI50 values as low as 0.36 µM against certain ovarian cancer lines. Intriguingly, our research suggests a potential shift from purely cytotoxic towards more cytostatic behavior, potentially offering improved therapeutic windows and reduced side effects. Molecular docking studies provide evidence for the compounds' interaction with human carbonic anhydrase IX, hinting at a possible mechanism of action. This comprehensive study not only introduces a promising new class of anti-cancer compounds but also provides a rich foundation of structural, electronic, and biological data to fuel future research. The bithienylbenzamidine derivatives, particularly compound 4c, represent exciting candidates for further development in the ongoing battle against cancer.

CD74 is a potential biomarker predicting the response to immune checkpoint blockade

BackgroundImmune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.MethodsThe unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.ResultsIn this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.ConclusionsThe findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Impact of protein kinase CK2 downregulation and inhibition on oncomir clusters 17 ~ 92 and 106b ~ 25 in prostate, breast, and head and neck cancers

BackgroundProtein kinase CK2 is a ubiquitous and highly conserved protein Ser/Thr kinase with diverse cell functions. CK2 is upregulated in various cancers and affects numerous aspects of their underlying pathobiology. The important role of microRNAs (miRNAs) referred to as oncomirs is also recognized in various cancers. Elevation of both CK2 and altered miRNA expression in cancers raised the question whether there was a connection between CK2 function and oncomirs in cancer.MethodsPCR array analysis was used to examine the effects of CK2 siRNA-mediated downregulation on miRNA levels in C4-2 prostate cancer cells. We employed prostate cancer, breast cancer, and head and neck squamous cell carcinoma (HNSCC) cells as well as a prostate cancer xenograft orthotopic tumor model to examine the effects of CK2 siRNA-mediated downregulation or chemical inhibition on oncomir cluster miR-17 ~ 92 and miR-106b ~ 25 constituent miRNAs by quantitative reverse-transcriptase stem-loop PCR. Pri-miRNAs were measured in cancer cell lines by quantitative reverse-transcriptase PCR. Protein levels were assessed by western blot. PC3-LN4 prostate cancer orthotopic xenograft tumors and blood were collected from nude mice following repeated treatments with tenfibgen ligand nanocapsules containing RNAi-CK2 or RNAi-Control cargoes.ResultsPCR array analysis demonstrated effect on a subset of miRNAs following CK2 downregulation; we focused our investigation on CK2 regulation of miR-17 ~ 92 and 106b ~ 25 oncomir clusters. Chemical inhibition or molecular downregulation of CK2 greatly reduced expression of miR-17 ~ 92 and 106b ~ 25 in prostate, breast and head and neck cancer cells in vitro. CK2α and CK2α´ protein levels were significantly correlated with many of the miR-17 ~ 92 and some of the miR-106b ~ 25 constituent members in prostate cancer cells. Decreased pri-miRNA levels for the miR-17 ~ 92 gene cluster transcript were observed for 5 of 6 cancer cell lines tested following CK2 downregulation. Nanocapsule-mediated delivery of RNAi-CK2 reduced CK2 protein expression in orthotopic prostate xenograft tumors and decreased intra-tumoral and serum levels of the oncomirs.ConclusionsTargeting CK2 for the development of new cancer therapies is under active investigation in many laboratories and pharmaceutical companies. Our data suggest a new role for CK2 in cell signaling and survival in multiple cancer types through maintenance of miR-17 ~ 92 and 106b ~ 25 biogenesis.

Unveiling the pan-cancer landscape of S100A16: A comprehensive analysis of prognostic significance, drug sensitivity, and immunomodulatory roles.

Accumulating evidence supports the notion that S100A16 exhibits differential expression in many human cancers, affecting cellular functions associated with tumorigenesis through various signaling pathways. While extensive research has been conducted on S100A16 in specific cancer types, a comprehensive evaluation of its role across diverse cancers remains lacking. To explore the prognostic significance, drug sensitivity, and immunomodulatory roles of S100A16, a thorough analysis was conducted at a pan-cancer level using multiple databases. Our findings revealed high expression of S100A16 RNA in various human cancers. Importantly, this elevated expression was linked to disease prognosis and drug sensitivity across a spectrum of cancers. Genetic alterations in S100A16 were characterized across multiple cancer types, and a confirmed correlation was observed in the prognosis of skin cutaneous melanoma (SKCM). Furthermore, our study demonstrated a significant association between S100A16 expression and the infiltrating levels of diverse cell types in the tumor microenvironment (TME), suggesting its potential as a prognosis predictor for immunotherapy. Novel collections of miRNAs, such as has-miR-423-5p, has-miR-769-5p, has-miR-151a-3p, and has-miR-550a-5p, targeting S100A16 at a pan-cancer level were predicted through various databases. These findings contribute to a comprehensive understanding the role of S100A16 in prognosis prediction, chemotherapy, and immunotherapy, providing valuable insights for identifying novel targets in cancer treatment.

CASTOR1 phosphorylation predicts poor survival in male patients with KRAS-mutated lung adenocarcinoma

BackgroundLung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. We have previously shown a tumor suppressive role of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1), which is targeted for degradation upon phosphorylation at S14 (pCASTOR1) in multiple types of cancer. This study focuses on the predictive value of pCASTOR1 in lung adenocarcinoma (LUAD) patients with KRAS mutations.ResultsEmploying a newly developed pCASTOR1 specific antibody, we found that tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells (P < 0.05). Higher pCASTOR1 scores predicted poorer overall survival (OS) (HR = 3.3, P = 0.0008) and relapse-free survival (RFS) (HR = 3.0, P = 0.0035) in male patients with KRAS mutations. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations, akin to late-stage patients.ConclusionElevated pCASTOR1 scores serve as biomarkers predicting poorer OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.

Exploring the role of ADAMTSL2 across multiple cancer types: A pan-cancer analysis and validated in colorectal cancer

BackgroundRecent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD).MethodPan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters.ResultsADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p < 0.05). Kaplan‒Meier survival curves demonstrated that the high ADAMTSL2 group had a shorter OS time (p = 0.047) and progression free survival time (p = 0.026) than the low ADAMTSL2 group.ConclusionIn summary, we conducted a comprehensive pan-cancer analysis of ADAMTSL2 and we demonstrated that ADAMTSL2 may serve as a novel prognostic biomarker and immunotherapy target in COADREAD.

Pan-cancer analysis of TP53 mutations and their association with liver cancer and aristolochic acids

Liver cancer is a major global health concern, as its incidence continues to rise in numerous countries, making it a leading cause of cancer-related deaths. The TP53 gene, which encodes the p53 tumor suppressor protein, plays a crucial role in regulating cell growth and division. Mutations in TP53 have been implicated in increased risk for liver cancer development. In this study, we aim to conduct a pan-cancer analysis to further investigate the potential role of TP53 mutations in various cancer types and their relationship with liver cancer. Additionally, we will explore the interplay between TP53 gene mutations, liver cancer, and exposure to Aristolochic acids (AAs). To achieve these goals, we will utilize data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) databases, enabling a comprehensive analysis of TP53 in the context of multiple cancer types.