Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

One-stage scalp reconstruction using single-layer dermal regeneration template and split-thickness skin graft: a case series.

PURPOSE: Scalp full-thickness defects reconstruction following the resection of skin carcinoma poses significant challenges due to scalp anatomy complexity and limited vascularity. Despite various techniques available, including tissue expansion and local flaps, no single method stands as the gold standard. Moreover, cases requiring adjuvant radiotherapy further complicate reconstruction, demanding durable solutions. This study explores the efficacy of Integra® Dermal Regeneration Template Single Layer (Integra DRTSL) followed by split-thickness skin grafting (STSG) in one-stage scalp reconstruction post oncologic resection. METHODS: A retrospective analysis was conducted on patients undergoing this procedure from January 2020 to October 2023. Surgical outcomes, including graft take rates, complications, and adjuvant therapy tolerability, were assessed. RESULTS: Results demonstrated successful reconstruction in the majority of cases, with a complete graft take rate of 77% and minimal complications. Notably, the single-stage approach facilitated timely initiation of adjuvant therapy, crucial for oncologic management. Healing times were notably reduced (< 60 days), enabling early radiotherapy commencement. No local recurrences were observed during the 16-month follow-up. CONCLUSION: The use of Integra DRTSL with STSG in one-stage reconstruction presents a promising alternative, offering optimal cosmetic and functional outcomes with low complication rates. This approach streamlines the reconstruction process, ensuring timely adjuvant therapy initiation and maximizing patient outcomes, especially in the context of scalp cutaneous tumors requiring radiotherapy. CLINICAL TRIAL NUMBER: This research was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of University of Campania "Luigi Vanvitelli" (protocol code N. 0013333, 29 April 2021).

Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Analysis of Saliva as a Diagnostic Specimen for Rapid Classification of Oral Squamous Cell Carcinoma Using Chemometrics Methods.

BACKGROUND & AIM: Recent advancements in analytical techniques have highlighted the potential of Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy as a quick, cost-effective, non-invasive, and efficient tool for cancer diagnosis. This study aims to evaluate the effectiveness of ATR-FTIR spectroscopy in combination with supervised machine learning classification models for diagnosing OSCC using saliva samples. METHODS & MATERIALS: Eighty unstimulated whole saliva samples from OSCC patients and healthy controls were collected. The ATR-FTIR spectroscopy was performed and spectral data were used to classify healthy and OSCC groups. The data were analyzed using machine learning classification methods such as Partial Least Squares-Discriminant Analysis (PLS-DA) and Support Vector Machine Classification (SVM-C). The classification performance of the models was evaluated by computing sensitivity, specificity, precision, and accuracy. RESULTS: The samples were classified into two classes based on their spectral data. The obtained results demonstrate a high level of accuracy in the prediction sets of the PLS-DA and SVM-C models, with accuracy values of 0.960 and 0.962, respectively. The OSCC group sensitivity values for both PLS-DA and SVM-C models was 1.00, respectively. CONCLUSION: The study indicates that ATR-FTIR spectroscopy, combined with chemometrics, is a potential method for the non-invasive diagnosis of OSCC using saliva samples. This method achieved high accuracy and the findings of this study suggest that ATR-FTIR spectroscopy could be further developed for clinical applications in OSCC diagnosis.

Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib.

BACKGROUND: Loss of heterozygosity (LOH) diminishes genetic diversity within cancer genomes. A tumour arising in an individual heterozygous for a functional and a loss-of-function (LoF) allele of a gene occasionally retain only the LoF allele. This can result in deficiency of specific protein activities in cancer cells, creating unique differences between tumour cells and normal cells of the individual. Such differences may constitute vulnerabilities that can be exploited through allele-specific therapies. METHODS: To discover frequently lost genes with prevalent LoF alleles, we mined the 1000 Genomes dataset for SNVs causing protein truncation through base substitution, indels or splice site disruptions, resulting in 60 LoF variants in 60 genes. From these, the variant rs3892097 in the liver enzyme CYP2D6 was selected because it is located within a genomic region that frequently undergoes LOH in several tumor types including hepatocellular cancers. To evaluate the relationship between CYP2D6 activity and the toxicities of anticancer agents, we screened 525 compounds currently in clinical use or undergoing clinical trials using cell model systems with or without CYP2D6 activity. FINDINGS: We identified 12 compounds, AZD-3463, CYC-116, etoposide, everolimus, GDC-0349, lenvatinib, MK-8776, PHA-680632, talazoparib, tyrphostin 9, VX-702, and WZ-3146, using an engineered HEK293T cell model. Of these, talazoparib and MK-8776 demonstrated consistently heightened cytotoxic effects against cells with compromised CYP2D6 activity in engineered hepatocellular cancer cell models. Moreover, talazoparib displayed CYP2D6 genotype dependent effects on primary hepatocellular carcinoma organoids. INTERPRETATION: Exploiting the loss of drug-metabolizing enzyme gene activity in tumor cells following loss of heterozygosity could present a promising therapeutic strategy for targeted cancer treatment. FUNDING: This work was funded by Barncancerfonden (T.S, PR2022-0099 and PR2020-0171, X.Z, TJ2021-0111), Cancerfonden (T.S, 211719Pj and D.G, 222449Pj), Vetenskapsrådet (T.S, 2020-02371 and D.G, 2020-04707), and the Erling Persson Foundation (T.S, 2020-0037 and T.S, 2023-0113).

Diagnostic and prognostic potential of the intra-tumoral microbiota profile in HPV-independent endocervical adenocarcinoma.

Background: Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Objective: Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. Methods: We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Results: Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. Conclusion: The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Oncological outcomes of minimally invasive surgery in non-endometrioid endometrial Cancer patients with varying prognostic risks: a retrospective cohort study based on the ESGO/ESTRO/ESP 2020 guidelines.

BACKGROUND: Non-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines. METHODS: A retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods. RESULTS: The study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062-7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate-risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001). CONCLUSION: This investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.

Unraveling the key role of chromatin structure in cancer development through epigenetic landscape characterization of oral cancer.

Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report.

BACKGROUND: Rectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin. CASE PRESENTATION: A 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence. CONCLUSION: This case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.

Evaluation of CTLA-4 and PD-L1 Expression in Thyroid Carcinoma and Its Prognostic Significance.

Introduction Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) have revolutionised treatment and improved outcomes in various malignancies. We aimed to evaluate CTLA-4 and PD-L1 immunoexpression in thyroid tumours and correlated them with clinicopathological parameters. Methods The study included 90 cases of thyroid malignancies comprising papillary thyroid carcinoma (PTC) (n = 64, 54.2%), follicular thyroid carcinoma (FTC) (n = 19, 16.1%), anaplastic thyroid carcinoma (ATC) (n = 3, 2.5%), and poorly differentiated carcinoma (n = 4, 3.4%), two cases (1.69%) of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) along with 26 cases (22%) of benign thyroid lesions. CTLA-4 (UMAB249) and PD-L1 (SP263) expression were assessed in all the cases of thyroid tumours. Results were compared with clinicopathologic parameters and overall survival. Results PD-L1 was positive in all three cases of anaplastic thyroid carcinoma (ATC), 33% (n = 21) cases of PTC, and 16% (n = 3) cases of FTC. PD-L1 positivity was significantly associated at tumour proportion score (TPS) ≥1% with lymphovascular invasion and age ≤40 years and at TPS ≥50% with tumour necrosis and N-stage. Immune proportion score (IPS) did not correlate with any clinicopathological parameters except for the N-stage. CTLA-4 was positive in six cases of PTC (1-5%); five showed lymph node involvement (p = 0.032). IPS was positive in 14 cases, and a significant association was seen with lymph node metastasis, lymphocytic infiltration, and lymphovascular invasion. Three cases of PTC showed co-expression for PD-L1 and CTLA-4 in tumour cells. No significant association was seen between PD-L1 expression and survival. Conclusion The current data suggest that PD-L1 is expressed in differentiated thyroid carcinoma, mainly PTC and ATC, indicating higher responsiveness to immunotherapy. A subset of PTC showed co-expression of PD-L1 and CTLA-4. These findings suggest the need for further investigation to utilise combinational immunotherapy, including anti-PD-L1 and anti-CTLA-4.

Adenosquamous carcinoma arising within a long-standing intrapulmonary bronchogenic cyst in an adult presenting with hyponatraemia.

A 74-year-old woman's persistent hyponatraemia led to the discovery of an adenosquamous carcinoma within an intrapulmonary bronchogenic cyst (IPBC), diagnosed 59 years prior. This is the first reported case of such a transformation in an IPBC. An adenosquamous carcinoma, originating from an intrapulmonary bronchogenic cyst identified 59 years prior, was discovered during the workup for a patient's unexplained, persistent hyponatraemia.

An Abscopal Effect on Lung Metastases in Canine Mammary Cancer Patients Induced by Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Nanoparticles and Anti-Canine PD-1.

Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events. We found that acPD-1 and CPMV/acPD-1 injections resulted in tumor control and a reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of treated dogs. In two metastatic CMC patients, CPMV/acPD-1 treatments resulted in the control and reduction of established lung metastases. CPMV/acPD-1 treatments were associated with altered gene expression related to TLR1-4 signaling and complement pathways. These novel therapies could be effective for CMC patients. Owing to the extensive similarities between CMC and human BC, IT CPMV combined with approved anti-PD-1 therapies could be a novel and effective immunotherapy to treat local BC and suppress metastatic BC.

Genomic Amplification of TBC1D31 Promotes Hepatocellular Carcinoma Through Reducing the Rab22A-Mediated Endolysosomal Trafficking and Degradation of EGFR.

Hepatocellular carcinomas (HCCs) are characterized by a vast spectrum of somatic copy number alterations (CNAs); however, their functional relevance is largely unknown. By performing a genome-wide survey on prognosis-associated focal CNAs in 814 HCC patients by an integrative computational framework based on transcriptomic data, genomic amplification is identified at 8q24.13 as a promising candidate. Further evidence is provided that the 8q24.13 amplification-driven overexpression of Rab GTPase activating protein TBC1D31 exacerbates HCC growth and metastasis both in vitro and in vivo through activating Epidermal growth factor receptor (EGFR) signaling. Mechanistically, TBC1D31 acts as a Rab GTPase activating protein to catalyze GTP hydrolysis for Rab22A and then reduces the Rab22A-mediated endolysosomal trafficking and degradation of EGFR. Notably, overexpression of TBC1D31 markedly increases the resistance of HCC cells to lenvatinib, whereas inhibition of the TBC1D31-EGFR axis can reverse this resistance phenotype. This study highlights that TBC1D31 at 8q24.13 is a new critical oncogene, uncovers a novel mechanism of EGFR activation in HCC, and proposes the potential strategies for treating HCC patients with TBC1D31 amplification or overexpression.

Gallbladder Neuroendocrine Neoplasms in Dogs and Humans.

Gallbladder neuroendocrine neoplasms (GB NENs) are among the rarest cancers reported in humans and dogs. This review provides a detailed review of the canine GB NEN literature and an interspecies comparison of demographics, clinical pathophysiology, pathobiology, and therapeutic response of GB NENs. The aim of this work is to explore the relevance of dogs as a spontaneous model for human GB NENs.

An Overview of Altered Pathways Associated with Sensitivity to Platinum-Based Chemotherapy in Neuroendocrine Tumors: Strengths and Prospects.

Neuroendocrine neoplasms (NENs) are a diverse group of malignancies with a shared phenotype but varying prognosis and response to current treatments. Based on their morphological features and rate of proliferation, NENs can be classified into two main groups with a distinct clinical behavior and response to treatment: (i) well-differentiated neuroendocrine tumors (NETs) or carcinoids (with a low proliferation rate), and (ii) poorly differentiated small- or large-cell neuroendocrine carcinomas (NECs) (with a high proliferation rate). For certain NENs (such as pancreatic tumors, higher-grade tumors, and those with DNA damage repair defects), chemotherapy is the main therapeutic approach. Among the different chemotherapic agents, cisplatin and carboplatin, in combination with etoposide, have shown the greatest efficacy in treating NECs compared to NETs. The cytotoxic effects of cisplatin and carboplatin are primarily due to their binding to DNA, which interferes with normal DNA transcription and/or replication. Consistent with this, NECs, which often have mutations in pathways involved in DNA repair (such as Rb, MDM2, BRCA, and PTEN), have a high response to platinum-based chemotherapy. Identifying mutations that affect molecular pathways involved in the initiation and progression of NENs can be crucial in predicting the response to platinum chemotherapy. This review aims to highlight targetable mutations that could serve as predictors of therapeutic response to platinum-based chemotherapy in NENs.

Identification of prognostic RNA editing profiles for clear cell renal carcinoma.

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer and currently lacks effective biomarkers. This research aims to analyze and identify RNA editing profile associated with ccRCC prognosis through bioinformatics and in vitro experiments. Methods: Transcriptome data and clinical information for ccRCC were retrieved from the TCGA database, and RNA editing files were obtained from the Synapse database. Prognostic models were screened, developed, and assessed using consistency index analysis and independent prognostic analysis, etc. Internal validation models were also constructed for further evaluation. Differential genes were investigated using GO, KEGG, and GSEA enrichment analyses. Furthermore, qPCR was performed to determine gene expression in human renal tubular epithelial cells HK-2 and ccRCC cells A-498, 786-O, and Caki-2. Results: An RNA editing-based risk score, that effectively distinguishes between high and low-risk populations, has been identified. It includes CHD3| chr17:7815229, MYO19| chr17:34853704, OIP5-AS1| chr15:41590962, MRI1| chr19:13883962, GBP4| chr1:89649327, APOL1| chr22:36662830, FCF1| chr14:75203040 edited sites or genes and could serve as an independent prognostic factor for ccRCC patients. qPCR results showed significant up-regulation of CHD3, MYO19, MRI1, APOL1, and FCF1 in A-498, 786-O, and Caki-2 cells, while the expression of OIP5-AS1 and GBP4 was significantly down-regulated. Conclusion: RNA editing site-based prognostic models are valuable in differentiating between high and low-risk populations. The seven identified RNA editing sites may be utilized as potential biomarkers for ccRCC.

Lymph Node Metastasis in Gastrointestinal Carcinomas: A View from a Proteomics Perspective.

Lymph node metastasis (LNM) is one of the major prognostic factors in human gastrointestinal carcinomas (GICs). The lymph node-positive patients have poorer survival than node-negative patients. LNM is directly associated with the recurrence and poor survival of patients with GICs. The early detection of LNM in patients and designing effective therapies to suppress LNM may significantly impact the survival of these patients. The rapid progress made in proteomic technologies could be successfully applied to identify molecular targets for cancers at high-throughput levels. LC-MS/MS analysis enables the identification of proteins involved in LN metastasis, which can be utilized for diagnostic and therapeutic applications. This review summarizes the studies on LN metastasis in GICs using proteomic approaches to date.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.

Risk of lymph node metastasis in T1 tonsil squamous cell carcinomas patients according to age stratification at diagnosis.

BACKGROUND: The objective of this study is to assess the association between age and lymph nodes metastasis (LNM) in T1 tonsil squamous cell carcinomas (TSCC) patients. METHODS: Patients with T1 TSCC were extracted from the SEER database between 2005 and 2014. Univariate and multivariate logistic regression models were produced to recognize the association between age and risk factors of LNM. RESULTS: A total of 2430 patients were analyzed. Younger patients more frequently presented with LNM compared to their older peers (P < 0.01, respectively.). In multivariate analyses, older age was associated with a significantly lower risk of LNM. Compared to patients aged 29-39-years-old, the hazard ratios for patients aged 40-49, 50-59, 60-69, and 70-88 years old were 0.911 (95 % confidence interval [CI] 0.370-2.245), 0.641 (95 % CI 0.268-1.535), 0.511 (95 % CI 0.212-1.231), and 0.236 (95 % CI 0.095-0.584), respectively. Subgroups analysis shows that the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients (P < 0.05, respectively). CONCLUSION: Our study demonstrates that younger patients with T1 TSCC had a higher risk of LNM than their old peers and the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients. More accurate assessments of LNM and prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck will be imperative for reducing recurrence in younger T1 TSCC.