Molecular analysis of genetic mutations in non-small cell lung cancer in Morocco.

Non-small cell lung cancer (NSCLC) is a significant global health issue with diverse molecular profiles affecting treatment responses. Yet, NSCLC's molecular epidemiology in Morocco is largely unexplored. This study focuses on NSCLC genetic mutations, specifically in adenocarcinoma, among Moroccan patients to contribute to understanding NSCLC in this population. Ninety-four patients diagnosed with lung adenocarcinoma were analyzed. Formalin-fixed paraffin-embedded tissue samples were processed, and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) was extracted using standardized protocols. Mutations were detected using the AmoyDx Pan Lung Cancer Polymerase Chain Reaction (PCR) Panel kit, and their frequencies were assessed through statistical analysis. Epidermal Growth Factor Receptor (EGFR) mutations were detected in 22.34% of patients, predominantly exon 19 deletions (66.66%) and exon 21 L858R mutations (23.80%). Anaplastic lymphoma kinase (ALK) gene fusion was observed in 3.19% of patients, and KRAS mutations in 1.06%. No mutations were found in other tested genes. A slightly higher mutation rate was noted in females (54.16%) compared to males (45.84%). The study reveals a distinct mutation profile in Moroccan NSCLC patients, with a notable prevalence of EGFR mutations, albeit lower than in some Asian populations. The significance of EGFR mutations in treatment response aligns with global findings, highlighting the importance of understanding regional molecular variations for personalized therapy. Despite limitations in sample size and clinical data, this study sheds light on the genetic landscape of NSCLC in Morocco. The observed mutation rates, particularly in EGFR, underscore the potential for targeted therapies in Moroccan NSCLC patients, emphasizing the need for further research to refine treatment strategies tailored to this population.

Antitumor activity and phenolic profile of Melissa officinalis extract against human gastric adenocarcinoma cells.

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.

The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

[Correlation between common driver gene variations and clinicopathological typing in lung adenocarcinoma].

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.

[Application of PRAME immunohistochemistry in the differential diagnosis of primary endometrial and endocervical adenocarcinomas].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

[Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study].

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Premature mortality for patients after completely resected early adenocarcinoma of the esophagus or stomach.

OBJECTIVE: To establish the life expectancy burden of esophago-gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. BACKGROUND: For patients with early EAC or GAC, the short-term prognosis after surgical resection is very good. Little data is available regarding long-term prognosis when compared to the general population. METHODS: Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en-bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2-lymphadenectomy. Surviving patients had a median follow-up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. RESULTS: Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow-up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. CONCLUSION: After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies.

Immunohistochemical Human Epidermal Growth Factor Receptor 2 (HER2) Expression Pattern in Gastric Adenocarcinomas in a Nigerian Tertiary Hospital.

BACKGROUND AND OBJECTIVE: The demonstration of HER2 in gastric adenocarcinoma (GA) tissues by immunohistochemistry assists in deciding whether targeted therapy would optimise the treatment of GA patients who are HER2 positive. However, this has not been extensively studied in our patients hence the need for this study. METHODS: Recipient tissue microarray blocks were constructed from donor archival formalin fixed paraffin embedded gastric tumour tissue from 80 patients seen over a period of 17 years in a retrospective descriptive study. Slides cut from these blocks were stained with antihuman HER2 antibody by immunohistochemistry and scored using the trastuzumab in gastric adenocarcinomas (ToGA) trial criteria. Data on age, gender, site of lesion and histological subtype of the gastric adenocarcinomas were also retrieved and reviewed. RESULTS: Eighty cases (52 males and 28 females; male to female ratio of 1.9:1), 55.65 ±13.50 years (modal age group 60-69 years), were studied. Most tumours (91.2%) involved the distal parts (pylorus, antrum and body) with a few (8.8%) involving the proximal part (cardia and fundus) of the stomach. HER2 was overexpressed in a total of 6 (7.5%) cases only. Two of seven (28.6%) proximal tumours showed HER2 positivity whereas only 4 of 73 (5.5%) of the distal tumours showed HER2 positivity. CONCLUSION: We had only a slightly lower HER2 overexpression rate than in studies from many other parts of the world. The observed overexpression was significantly higher in proximal than distally located tumours suggesting that distal tumours are less likely to respond to Trastuzumab than proximal tumours. The known association of distal gastric tumours with Helicobacter pylori infection probably provides for a possible difference in the molecular aetiopathogenesis of GAs by site of occurrence. The exact mechanisms for proximal gastric carcinogenesis remain to be more clearly elucidated. More studies, including clinical trials with larger sample sizes, are recommended to elucidate this differential expression of HER2 in gastric adenocarcinoma.

CONTEXTE ET OBJECTIF: La démonstration de la présence de HER2 dans les tissus d'adénocarcinome gastrique (AG) par immunohistochimie aide à décider si une thérapie ciblée optimiserait le traitement des patients atteints d'AG HER2 positif. Cependant, cela n'a pas été largement étudié chez nos patients, d'où la nécessité de cette étude. MÉTHODES: Des blocs de microarray de tissus destinataires ont été construits à partir de tissus tumoraux gastriques inclus en paraffine d'archives provenant de 80 patients vus sur une période de 17 ans, dans le cadre d'une étude descriptive rétrospective. Les lames découpées à partir de ces blocs ont été colorées avec un anticorps anti-HER2 humain par immunohistochimie et évaluées selon les critères de l'essai trastuzumab dans les adénocarcinomes gastriques (ToGA). Les données sur l'âge, le sexe, le site de la lésion et le sous-type histologique des adénocarcinomes gastriques ont également été récupérées et examinées. RÉSULTATS: Quatre-vingts cas (52 hommes et 28 femmes ; rapport hommes-femmes de 1,9:1), 55,65 ± 13,50 ans (groupe d'âge modal 60-69 ans), ont été étudiés. La plupart des tumeurs (91,2 %) ont touché les parties distales (pylore, antre et corps) avec quelques-unes (8,8 %) touchant la partie proximale (cardia et fundus) de l'estomac. HER2 a été surexprimé dans un total de 6 cas seulement (7,5 %). Deux des sept tumeurs proximales (28,6 %) ont montré une positivité HER2, tandis que seulement 4 des 73 tumeurs distales (5,5 %) ont montré une positivité HER2. CONCLUSION: Nous avons eu un taux de surexpression de HER2 légèrement inférieur à celui observé dans de nombreuses autres régions du monde. La surexpression observée était significativement plus élevée dans les tumeurs proximales que dans les tumeurs distales, suggérant que les tumeurs distales sont moins susceptibles de répondre au trastuzumab que les tumeurs proximales. L'association connue des tumeurs gastriques distales avec l'infection par Helicobacter pylori fournit probablement une différence potentielle dans l'étiopathogenèse moléculaire des AG par site d'occurrence. Les mécanismes exacts de la carcinogenèse gastrique proximale restent à élucider plus clairement. Davantage d'études, y compris des essais cliniques avec des tailles d'échantillons plus importantes, sont recommandées pour élucider cette expression différentielle de HER2 dans l'adénocarcinome gastrique. MOTS-CLÉS: Adénocarcinome gastrique, expression de HER2, Immunohistochimie, Thérapie ciblée.

NSUN6 mediates 5-methylcytosine modification of METTL3 and promotes colon adenocarcinoma progression.

Colon adenocarcinoma (COAD) is a common and fatal malignant tumor of digestive system with complex etiology. 5-Methylcytosine (m5C) modification of RNA by the NSUN gene family (NSUN1-NSUN7) and DNMT2 reshape cell biology and regulate tumor development. However, the expression profile, prognostic significance and function of these m5C modifiers in COAD remain largely unclear. By mining multiple integrated tumor databases, we found that NSUN1, NSUN2, NSUN5, and NSUN6 were overexpressed in COAD tumor samples relative to normal samples. Clinically, high expression of NSUN6 was significantly associated with shorter survival (including both disease-free survival and overall survival) in COAD patients. NSUN6 was further confirmed to be upregulated at both tissue and cellular levels of COAD, suggesting that NSUN6 plays a critical role in disease progression. Through comprehensive gene enrichment analysis and cell-based functional validation, it was revealed that NSUN6 promoted the cell cycle progression and cell proliferation of COAD. Mechanistically, NSUN6 upregulates the expression of oncogenic METTL3 and catalyzes its m5C modification in COAD cells. Overexpression of METTL3 significantly relieved the cell cycle inhibition of COAD caused by NSUN6 deficiency. Furthermore, NSUN6 was negatively associated with the abundance of infiltrating immune cells in COAD tumors, such as activated B cells, natural killer cells, effector memory CD8 T cells, and regulatory T cells. Importantly, pan-cancer analysis further uncovered that NSUN6 was dysregulated and heterogeneous in various tumors. Thus our findings extend the role of m5C transferase in COAD and suggest that NSUN6 is a potential biomarker and target for this malignancy.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

MISP Is Overexpressed in Intestinal Metaplasia and Gastric Cancer.

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.

Single-cell and spatial transcriptomics analysis of non-small cell lung cancer.

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional "reprogramming" of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

SKA3 Expression as a Prognostic Factor for Patients with Pancreatic Adenocarcinoma.

The spindle and kinetochore-associated complex subunit 3 (SKA3) is a protein essential for proper chromosome segregation during mitosis and thus responsible for maintaining genome stability. Although its involvement in the pathogenesis of various cancer types has been reported, the potential clinicopathological significance of SKA3 in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Therefore, this study aimed to assess clinicopathological associations and prognostic value of SKA3 in PDAC. For this purpose, in-house immunohistochemical analysis on tissue macroarrays (TMAs), as well as a bioinformatic examination using publicly available RNA-Seq dataset, were performed. It was demonstrated that SKA3 expression at both mRNA and protein levels was significantly elevated in PDAC compared to control tissues. Upregulated mRNA expression constituted an independent unfavorable prognostic factor for the overall survival of PDAC patients, whereas altered SKA3 protein levels were associated with significantly better clinical outcomes. The last observation was particularly clear in the early-stage tumors. These findings render SKA3 a promising prognostic biomarker for patients with pancreatic ductal adenocarcinoma. However, further studies are needed to confirm this conclusion.

Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

Content and tissue expression of Collagen I, Collagen IV, and Laminin in the Extracellular Matrix in Prostate Adenocarcinoma.

Prostate cancer is one of the most common neoplasm in the male population. It is not known why some tumors become more aggressive than others. Although most studies show changes in the expression of cell adhesion molecules and the extracellular matrix correlated with the Gleason score, no study has objectively measured the tissue content of these molecules. This study aims to measure the content and tissue expression of collagen type I and IV and laminin in the extracellular matrix of patients with prostate adenocarcinoma and correlate these findings with the Gleason score and clinical characteristics. Forty-one patients who underwent radical prostate surgery at the Urology Department of a reference Hospital in Brazil between January 2015 and December 2020 were studied. The tissue protein content was estimated under light microscopy at a final magnification of 200 × . The mean collagen I score in prostate adenocarcinoma tissue samples was 7.16 ± 1.03 pixels/field. The mean type IV collagen score was 3.44 ± 0.61 pixels/field. The mean laminin score was 5.19 ± 0.79 pixels/field. The total Gleason score was correlated with both collagen and laminin. All the correlations were negative, which shows that the higher the collagen/laminin expression was, the lower the total Gleason score (p-value < 0,05). According to the Pearson correlation analysis, age has no statistical relationship with collagen and laminin content. PSA, in turn, showed a correlation only with laminin, but r = -0.378 (p = 0.015). Among the associated diseases and lifestyle habits, there is only statistical significance in the comparison of alcoholism for collagen I. For collagen IV and laminin, no statistical significance was obtained with the clinical variables analyzed.

An isolated vaginal metastasis from rectal cancer: a case report.

INTRODUCTION: Vaginal metastasis from colorectal cancer is a rare occurrence, typically associated with other metastatic lesions. Isolated metastasis is exceedingly uncommon, with only a few cases documented in the literature. Vaginal involvement in colorectal cancer primarily results from direct contiguous spread from the primary tumor. CASE PRESENTATION: We present the case of a 70-year-old African woman diagnosed with adenocarcinoma of the middle rectum. She underwent chemotherapy, radiotherapy, and subsequent anterior resection. After 2 months, an isolated metastasis of rectal cancer was identified in the lower third of the left vaginal wall, confirmed by biopsy. Colonoscopy ruled out colorectal recurrence. Thoraco-abdominal computed tomography scan showed no distant metastases. The patient underwent abdominoperineal resection, removing the lateral and posterior vaginal wall with free macroscopic margins and a definitive colostomy. The final histopathological analysis confirmed the diagnosis of moderately differentiated adenocarcinoma of the vagina, measuring 5 × 4.5 cm. The rectal wall was extrinsically invaded by the tumor down to the muscularis propria while respecting the rectal mucosa. Resection margins were negative. The patient was discharged 1 week postoperation with no complications. Adjuvant chemotherapy was indicated, and the patient is currently tolerating the treatment well. CONCLUSION: Vaginal metastases from colorectal cancer are extremely rare. A vigilant gynecological examination is recommended during the follow-up of colorectal cancer patients. Diagnosis can be challenging, especially if the metastatic lesion is small and asymptomatic, even after standard radiological examination. Surgical resection followed by chemotherapy is a valid option for patients with early isolated metastases.

Identification of extracellular matrix-related biomarkers in colon adenocarcinoma by bioinformatics and experimental validation.

Backgrounds: Extracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis. Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial-mesenchymal transition (EMT). Results: Three potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model. Conclusion: The three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.

Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.