Clinicopathological Stage Research Articles

An immune infiltration-related long non-coding RNAs signature predicts prognosis for hepatocellular carcinoma.

Background: With a high incidence and dismal survival rate, hepatocellular carcinoma (HCC) tops the list of the world's most frequent malignant tumors. Immunotherapy is a new approach to cancer treatment, and its effect on prolonging overall survival (OS) varies from patient to patient. For a more effective prognosis and treatment of HCC, we are committed to identifying immune infiltration-related long non-coding RNAs (IIRLs) with prognostic value in hepatocellular carcinoma. Methods: In our study, we calculated immune scores of 369 hepatocellular carcinoma samples from the Cancer Genome Atlas (TCGA) database by using an estimation algorithm, and obtained long non-coding RNAs (lncRNAs) associated with immune infiltration by using Weighted Gene Co-expression Network analysis (WGCNA). For training cohort, univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis were used to determine prognostic IIRLs, we established a prognostic IIRLs signature. By testing cohort and entire cohort, we confirmed that the signature is practical. The prognosis of people with different clinicopathological stages and risk scores were predicted by the nomogram we constructed. In addition, Immune cell infiltration analysis and prediction of therapeutic drugs were performed. Results: 93 IIRLs were obtained by WGCNA. Furthermore, the prognostic value of these IIRLs were evaluated by using univariate Cox, Lasso and multivariate Cox analysis. Four IIRLs were used to create a signature with a prognosis. Time-related receiver operating characteristic (ROC) curve revealed that this model had an acceptable prognostic value for HCC patients. By using univariate and multivariate Cox regression analysis, this risk score has been shown to be an independent prognostic factor for HCC. The nomogram we made showed good predictions. Except for that, the treatment with immune checkpoint inhibitors (ICI) was likely to be more effective for low-risk patients. Conclusion: Based on four IIRLs, a prognostic signature was created in this research showed good accuracy in predicting OS. This study also provided valuable references for Immunotherapy of hepatocellular carcinoma.

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis is still unclear. The present study aimed to investigate the role of miR-202-3p and its downstream target gene, ribonucleotide reductase regulatory subunit M2 (RRM2), in the occurrence and development of LUAD and elucidate the correlation between RRM2 and the clinicopathological stage and prognosis of LUAD. The expression of miR-202-3p was analyzed using the CancerMIRNome database and quantitative polymerase chain reaction (qPCR). The effects of miR-202-3p and RRM2 on the proliferation, migration, and invasion of A549 cells were analyzed. A dual luciferase reporter assay was used to verify the targeting of miR-202-3p and RRM2. Additionally, the correlation between RRM2 expression and clinicopathology was analyzed. (I) MiR-202-3p was lowly expressed in LUAD and the LUAD cell lines. qPCR confirmed that microRNA (miRNA) transfection was effective and sufficient for subsequent experiments. (II) MiR-202-3p inhibited the proliferation, invasion, and migration of LUAD cells. (III) There was a targeting relationship between miR-202-3p and RRM2, and miR-202-3p affected the expression of the RRM2 protein. RRM2 was highly expressed in lung cancer tissue. (IV) RRM2 was associated with the clinicopathological staging of lung cancer. The prognosis of patients with low RRM2 expression was better, and the prognostic sensitivity of RRM2 to lung cancer was high. RRM2 may exert its effects via the Notch pathway. (V) Si-RRM2 inhibited the expression of the RRM2 protein. RRM2 promoted the proliferation, migration, and invasion of LUAD cells. A miR-202-3p inhibitor restored the inhibitory effect of si-RRM2 on LUAD cells. MiR-202-3p was lowly expressed in lung cancer tissue. MiR-202-3p overexpression inhibited the proliferation and metastasis of lung cancer cells. RRM2 was highly expressed in lung cancer tissue and promoted the proliferation and metastasis of lung cancer cells. MiR-202-3p targeted and inhibited RRM2, thereby reducing the proliferation and metastasis of LUAD cells. LUAD patients with low RRM2 expression had a better prognosis, and the expression level of RRM2 was correlated with the clinical characteristics of lung cancer patients.

Cytodiagnosis of rhinoscleroma and its morphological clues: Our experience with four cases

Rhinoscleroma, a chronic progressive inflammatory disease of the upper respiratory tract, has a prolonged course and passes through three overlapping clinicopathologic stages. The histopathology findings are well illustrated in the literature; however, there is a paucity of reports explaining cytomorphological features of rhinoscleroma. It is the proliferative stage when disease presents as a nodular mass which can be targeted for cytological study. Here, the authors report fine-needle aspiration (FNA) cytology of four cases of rhinoscleroma who presented with intranasal firm, nodular lesions; its cytology revealed numerous, large, singly scattered histiocytes in a dense inflammatory background of lymphocytes, plasma cells, and few eosinophils. The microorganisms were visualized as intracytoplasmic loosely clustered, short rods within the histiocytes (Mikulicz cells) in May-Grunwald-Giemsa (MGG) smears. FNA sampling of rhinoscleroma in its nodular stage can yield classic cytomorphology with demonstration of organisms on air-dried smears which can further substantiate the cytodiagnosis. Thus, high index of suspicion and diligent search can aid in early and accurate diagnosed even on cytology with the help of conventional wet fixed Pap and air-dried MGG stain; both being complementary to each other and further can be supported with special stains such as periodic acid–Schiff stain or Gram whenever required.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment

Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancers owing to high invasiveness and high metastatic potential. Tumor microenvironment (TME) provides powerful evidences for discerning SKCM, raising the prospect to identify biomarkers of SKCM. Based on the transcriptome profiles of patients with SKCM and the corresponding clinical information from The Cancer Genome Atlas (TCGA), we used ESTIMATE algorithm to calculate ImmuneScore and StromalScore and identified the TME-Related differentially expressed genes (DEGs), than the intersected TME-Related DEGs were used for subsequent functional enrichment analysis. Protein–protein interaction (PPI) analysis was used to identify the functionality-related DEGs and univariate Cox regression analysis was used to identify the survival-related DEGs. Furthermore, SKCM-related DEGs were identified based on two Gene Expression Omnibus (GEO) datasets. Finally, we intersected functionality-related DEGs, survival-related DEGs, and SKCM-related DEGs, ascertaining that six DEGs (CCL4, CXCL10, CCL5, GZMB, C1QA, and C1QB) function as core TME-related genes (CTRGs). Significant differences of GZMB, C1QA, and C1QB expressions were found in gender and clinicopathologic staging of SKCM. High levels of GZMB, C1QA, and C1QB expressions were associated with favorable prognosis. Gene set enrichment analysis (GSEA) showed that cell–cell interaction, cell behavior, and intracellular signaling transduction may be mainly involved in both C1QA, C1QB and GZMB expressions and metabolism of phospholipid and amino acid, transcription, and translation may be implicated in low GZMB expressions. C1QA, C1QB, and GZMB are novel SKCM-relating CTRGs, providing promising immune-related prognostic biomarkers for SKCM.

Enterotypical Prevotella and three novel bacterial biomarkers in preoperative stool predict the clinical outcome of colorectal cancer

BackgroundA significant proportion of colorectal cancer (CRC) patients suffer from early recurrence and progression after surgical treatment. Although the gut microbiota is considered as a key player in the initiation and progression of CRC, most prospective studies have been focused on a particular pathobionts such as Fusobacterium nucleatum. Here, we aimed to identify novel prognostic bacteria for CRC by examining the preoperative gut microbiota through 16S ribosomal RNA gene sequencing.ResultsWe collected stool samples from 333 patients with primary CRC within 2 weeks before surgery and followed up the patients for a median of 27.6 months for progression and 43.6 months for survival. The sequence and prognosis data were assessed using the log-rank test and multivariate Cox proportional hazard analysis. The gut microbiota was associated with the clinical outcomes of CRC patients (Pprogress = 0.011, Pdecease = 0.007). In particular, the high abundance of Prevotella, a representative genus of human enterotypes, indicated lower risks of CRC progression (P = 0.026) and decease (P = 0.0056), while the occurrence of Alistipes assigned to Bacteroides sp., Pyramidobacter piscolens, Dialister invisus, and Fusobacterium nucleatum indicated a high risk of progression. A microbiota-derived hazard score considering the five prognostic bacteria accurately predicted CRC progression in 1000 random subsamples; it outperformed widely accepted clinical biomarkers such as carcinoembryonic antigen and lymphatic invasion, after adjustment for the clinicopathological stage (adjusted HR 2.07 [95% CI, 1.61–2.64], P = 7.8e−9, C-index = 0.78). PICRUSt2 suggested that microbial pathways pertaining to thiamine salvage and L-histidine degradation underlie the different prognoses.ConclusionsThe enterotypical genus Prevotella was demonstrated to be useful in improving CRC prognosis, and combined with the four pathobionts, our hazard score based on the gut microbiota should provide an important asset in predicting medical outcomes for CRC patients.48KLrU1kw-NevPNeR-hyqwVideo

Evidence of Filamin A loss of solubility at the prodromal stage of neuropathologically-defined Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder diagnosed through the assessment of amyloid-beta (Aβ) and tau protein depositions. Filamin A (FLNA) could be a key partner of both Aβ and tau pathological processes and may be an important contributor to AD progression. The main aim of this study was to describe the differences in FLNA levels across clinicopathologic groups. From parietal cortex samples of 57 individuals (19 with no cognitive impairment (NCI), 19 mild cognitively impaired (MCI) and 19 with dementia) from the Religious Orders Study (ROS), we quantified total tau, phosphorylated tau (pTau), FLNA, synaptophysin, vesicular acetylcholine transporters (VAChT) and choline acetyltransferase (ChAT) by Western blot. Aβ42 and neuritic plaques (NP) were quantified by ELISA and Bielschowsky silver impregnation, respectively. AD staging was determined using ABC method combining Thal, Braak and the CERAD staging. From this, clinicopathologic stages of AD were established by subdividing subjects with neuropathological AD between preclinical AD, prodromal AD and AD dementia (ADD). Receiver operating characteristics analyses were performed to predict AD neuropathology from FLNA quantifications. Insoluble FLNA was significantly and positively correlated with Aβ42, NP, Thal stages, ABC scores and AD clinicopathologic stages (p < 0.05 False discovery rate-corrected). No correlation of FLNA with tau measures was found. Insoluble FLNA levels were significantly higher in the prodromal AD, ADD and intermediate ABC groups. This was consistent with significantly lower levels of soluble FLNA specifically in prodromal AD. Insoluble (AUC: 0.830) and soluble FLNA levels (AUC: 0.830) as well as the ratio of soluble over insoluble FLNA (AUC: 0.852), were excellent predictors of prodromal AD among subjects with MCI from the ROS cohort. We observed opposite level changes between insoluble and soluble FLNA in prodromal AD. As this stage coincides with the appearance of cognitive symptoms, this may be a key event in the transition from preclinical to prodromal AD. Insoluble FLNA could be useful to identify prodromal AD among subjects with an MCI, indicating that it might be a hallmark of prodromal AD.

Racial and ethnic differences in type II endometrial cancer mortality outcomes: The contribution of sociodemographic, clinicopathologic, and treatment factors

ObjectiveThe burden of type II endometrial cancer (EC) is rising dramatically in the U.S. Although type II EC disproportionately affects Black women, the magnitude of racial/ethnic differences in type II EC mortality outcomes and factors underlying these differences remain understudied. We examined racial/ethnic differences in cancer-specific and overall mortality in women with type II EC and quantified the extent to which mortality differences are mediated by sociodemographic, clinicopathologic, and treatment factors. Methods14,710 women ≥18 years with type II EC from 2007 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. The association between race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, and non-Hispanic Asian/Pacific Islander [NHAPI]) and cancer-specific and overall mortality was examined. Mediation analysis was used to identify factors underlying differences in mortality outcomes. ResultsNHB women had a higher risk of cancer-specific mortality than NHW women (hazard ratio [HR]: 1.22, 95% CI: 1.12–1.33), whereas NHAPI (HR: 0.88, 95% CI: 0.78–0.99) and Hispanic women (HR: 0.91, 95% CI: 0.81–1.01) had a lower risk of cancer-specific mortality than NHW women. Differences in clinicopathologic (stage, grade, histologic subtype), sociodemographic (insurance type, geographic region and location, neighborhood socioeconomic status), and treatment factors (treatment type, lymphadenectomy) explained 43.5%, 8.1%, and 7.3% of the difference in cancer-specific mortality between NHB and NHW women, respectively. Similar results were noted for overall mortality. ConclusionsMultidisciplinary and multilevel approaches that integrate and address social and biological factors are needed to reduce the disproportionate burden of type II EC mortality in NHB women.

Novel long noncoding RNA LINC02820 augments TNF signaling pathway to remodel cytoskeleton and potentiate metastasis in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. However, there are no targets to treat ESCC because the molecular mechanism behind the cancer is still unclear. Here, we found a novel long noncoding RNA LINC02820 was upregulated in ESCC and associated with the ESCC clinicopathological stage. Through a series of functional experiments, we observed that LINC02820 only promoted the migration and invasion capabilities of ESCC cell lines. Mechanically, we found that LINC02820 may affect the cytoskeletal remodeling, interact with splice factor 3B subunit 3 (SF3B3), and cooperate with TNFα to amplify the NF-κB signaling pathway, which can lead to ESCC metastasis. Overall, our findings revealed that LINC02820 is a potential biomarker and therapeutic target for the diagnosis and treatment of ESCC.

SLC11A1 associated with tumor microenvironment is a potential biomarker of prognosis and immunotherapy efficacy for colorectal cancer.

Colorectal cancer (CRC) is one of the most lethal cancers of the digestive system. The tumor microenvironment (TME) plays a central role in the initiation and development of CRC. However, little is known about the modulation mechanism of the TME in CRC. In our study, we attempted to identify a biomarker related to the TME modulation that could serve as a potential prognostic biomarker for CRC. We identified differentially expressed genes between the ImmuneScore high/low and StromalScore high/low groups. Using univariate COX regression analysis and hub gene analysis (cytoHubba), SLC11A1 was identified as the only candidate gene for subsequent analysis. CIBERSORT, EPIC, MCPcounter, and immunogenic cell death were performed to evaluate the effect of SLC11A1 on the TME. We also collected samples and performed Real-time quantitative PCR to verify the expression levels of SLC11A1 in CRC and adjacent normal tissues. The IMvigor210 cohort, TIDE score, and immunophenoscore (IPS) were used to analyze the association between SLC11A1 and immunotherapy efficacy. SLC11A1 was highly expressed in CRC tissues compared with its expression in normal colorectal tissues and was associated with poor prognosis and advanced clinicopathological stages. Gene set enrichment analysis showed that TGF-β pathways, JAK-STAT pathways, and angiogenesis were significantly enriched in the high-SLC11A1 group. Single-cell analysis validated the correlation between SLC11A1 and the TME. Using CIBERSORT, EPIC, and MCPcounter algorithms, we found that there was more macrophage and fibroblast infiltration in the SLC11A1 high-expression group. Meanwhile, high-SLC11A1 patients had lower IPS scores, higher TIDE scores, and fewer immunotherapy benefits than those of low-SLC11A1 patients. In conclusion, SLC11A1 plays a crucial role in the TME and could serve as a potential biomarker for poor prognosis and immunotherapy efficacy in CRC.

Implications of m6A-associated snRNAs in the prognosis and immunotherapeutic responses of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear. In this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups. Eight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy. Our study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.

The roles of BTG1 mRNA expression in cancers: A bioinformatics analysis.

BTG1 (B-cell translocation gene 1) may inhibit proliferation and cell cycle progression, induce differentiation, apoptosis, and anti-inflammatory activity. The goal of this study was to clarify the clinicopathological and prognostic significances of BTG1 mRNA expression and related signal pathways in cancers. Using the Oncomine, TCGA (the cancer genome atlas), xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal), and Kaplan-Meier plotter databases, we undertook a bioinformatics study of BTG1 mRNA expression in cancers. BTG1 expression was lower in gastric, lung, breast and ovarian cancer than normal tissue due to its promoter methylation, which was the opposite to BTG1 expression. BTG1 expression was positively correlated with dedifferentiation and histological grading of gastric cancer (p < 0.05), with squamous subtype and young age of lung cancer (p < 0.05), with infrequent lymph node metastasis, low TNM staging, young age, white race, infiltrative lobular subtype, Her2 negativity, favorable molecular subtyping, and no postmenopause status of breast cancer (p < 0.05), and with elder age, venous invasion, lymphatic invasion, and clinicopathological staging of ovarian cancer (p < 0.05). BTG1 expression was negatively correlated with favorable prognosis of gastric, lung or ovarian cancer patients, but the converse was true for breast cancer (p < 0.05). KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that the top signal pathways included cytokine-cytokine receptor interaction, cell adhesion molecules, chemokine, immune cell receptor and NF (nuclear factor)-κB signal pathways in gastric and breast cancer. The top hub genes mainly contained CD (cluster of differentiation) antigens in gastric cancer, FGF (fibroblast growth factor)-FGFR (FGF receptor) in lung cancer, NADH (nicotinamide adenine dinucleotide): ubiquinone oxidoreductase in breast cancer, and ribosomal proteins in ovarian cancer. BTG1 expression might be employed as a potential marker to indicate carcinogenesis and subsequent progression, even prognosis.

Multi-omics analysis of the oncogenic value of copper Metabolism-Related protein COMMD2 in human cancers.

The copper metabolism MURR1 domain (COMMD) protein family is involved in tumorigenicity of malignant tumors. However, as the member of COMMD, the role of COMMD2 in human tumors remains unknown. We used The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA) database, Cancer Cell Line Encyclopedia (CCLE) platform, univariate Cox regression analysis, Kaplan-Meier curve, cBioPortal, UALCAN database, Sangerbox online platform, GSCA database gene set enrichment analysis (GSEA), and GeneMANIA to analyze the expression of COMMD2, its prognostic values, genomic alteration patterns, and the correlation with tumor stemness, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrates, drug sensitivity, and gene function enrichment in pan-cancer. qRT-PCR, CCK-8, EdU, wound healing, and transwell migration assays were performed to confirm the function of COMMD2. COMMD2 was strongly expressed in most cancer types. Elevated COMMD2 expression affects the prognosis, clinicopathological stage, and molecular or immune subtypes of various tumors. Moreover, promoter hypomethylation and mutations in the COMMD2 gene may be associated with its high expression and poor survival. Additionally, we discovered that COMMD2 expression was linked to tumor stemness, TMB, MSI, immune cell infiltration, immune-checkpoint inhibitors, and drug sensitivity in pan-cancer. Furthermore, the COMMD2 gene co-expression network is constructed with GSEA analysis, displaying significant interaction of COMMD2 with E2F targets, G2-M checkpoint, and mitotic spindle in bladder cancer (BLCA). Finally, RNA interference data showed suppression of COMMD2 prevented proliferation and migration of BLCA and uterine corpus endometrial carcinoma (UCEC) cells. Our findings shed light on the COMMD2 functions in human cancers and demonstrate that it is a promising prognostic biomarker and therapeutic target in pan-cancer.

Diagnostic Approach for Acute Myeloid Leukemia Based on the World Health Organization Classification of Hematologic Neoplasms

Acute myeloid leukemias (AMLs) are heterogeneous hematologic neoplasms characterized by myeloblast or promyelocyte proliferation without normal differentiation. The World Health Organization (WHO) classifies AMLs on the basis of chromosomal and genetic aberrations, with different prognoses for each subtype. Therefore, accurate diagnosis and classification of AMLs is critical for timely and appropriate treatment. Initial diagnostic workup includes morphologic assessment of the bone marrow aspirate and trephine biopsies, immunophenotyping using flow cytometry or immunohistochemistry stains, chromosomal analysis using the G-banding technique or fluorescence in situ hybridization, and mutation analysis using polymerase chain reaction, direct sequencing, or next-generation sequencing. The present study provides an algorithm for AML diagnosis and classification based on the WHO criteria and describes different clinicopathological stages of the workup.

Real-World Evidence Shows Clinicians Appropriately Use the Prognostic 40-Gene Expression Profile (40-GEP) Test for High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients

Treatment decisions for patients with cutaneous squamous cell carcinoma (cSCC) are traditionally based upon clinicopathologic risk factors and staging systems. Due to the accuracy limitations of these resources in predicting poor outcomes, there is a clinically significant need for more accurate methods of risk assessment. The 40-gene expression profile (40-GEP) test was developed to augment metastatic risk prediction of high-risk cSCC patients and has been validated in two independent, multi-center studies involving over 1,000 patients. This study substantiates that the 40-GEP is appropriately utilized by clinicians and that the personalized risk-stratification results are impactful in guiding risk-aligned patient management.

Correlation of FOXA1 with some clinicopathological features, lymph node, grade, stage and tumor size

The Forkhead box (FOX) protein family includes FOXA1, and is a transcription factor (TF). It work as a pioneer factor, interacting with compressed chromatin to allow ER to bind more easily later (Nagaraj and Ma, 2021). It significantly contributed to the development and invasiveness of endocrine-resistant cells by changing the ER dependent transcriptome in numerous endocrine-resistant preclinical BC cell types (Chun et al., 2017). The present study is done during the period September 2021 and May 2022 at the University of Kufa's, Faculty of Medicine, Middle Euphrates Unit for Cancer Research. as a control group. These samples gathered from archives of the two private laboratories and re-evaluted by two pathologist. Positive nuclear IHC expression of FOXA1 is significantly reduced in 43 BC cases (58.9%) compared to 38 control persons (100%) while negative nuclear IHC expression of FOXA1 is significantly reduced in BC patients, 30 cases (41.1%) compared to 0 control persons (0.0%), Odd ratio 1.66, 95% CI (1.37-1.98), P=0.0001. Moreover, FOXA1 positivity was elevated significantly in patients with grade I and II (P=0.002) and absent of lymph node metastasis (p=0.027).

Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer.

BackgroundGallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC.MethodsThis was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves.ResultsB7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8+ TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction.ConclusionsImmune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary.

Centromere protein U is highly expressed in colorectal cancer and associated with a poor long-term prognosis

To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients. We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay. The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ2=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells. CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.

Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer.

The novel gene YBX3 is important for regulating translation and RNA catabolism and encodes a protein with a highly conserved cold-shock domain. However, its pathogenic roles across cancers (e.g., colon cancer) and its regulation remain unclear. We identified the pathogenic roles of YBX3 and its regulatory lncRNA HEIH in various cancers and investigated their effects on tumor progression in colon cancer. Methods including RNA pull-down, MS, and TMA of 93 patients, qPCR of 12 patients with diverse clinicopathologic stages, and western blotting were performed. The pancancer analysis showed that YBX3 expression varies significantly among not only cancer types but also molecular and immune subtypes of the same cancer. Furthermore, its expression in colon cancer is clinically significant, and there is an obvious negative regulatory association between HEIH and YBX3. Among various cancers, especially colon cancer, YBX3 is more related than HEIH expression to the clinical features and prognosis of subgroups. The receiver operating characteristic analysis showed that HEIH and YBX3 have similar predictive capacity in various cancers. The analysis of differentially expressed genes in colon cancer revealed that they have similar hub gene networks, indicating an oncogenic system with a strong overlap. The results also suggest that YBX3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by the tumor infiltration of immune cells. Interestingly, scRNA-seq revealed that HEIH inhibits this phenomenon. Our results also suggest that YBX3 expression is associated with immune or chemotherapeutic outcomes in various cancers, and YBX3 exhibited a higher predictive power than two of seven standardized biomarkers for response outcomes and overall survival of immune checkpoint blockade subcohorts. In colon cancer cell lines, lncRNA-HEIH and YBX3 associate. MS confirmed that YBX3 was pulled down with HEIH, and western blot showed that HEIH knockdown disinhibited YBX3. This study strongly suggests that lncRNA-HEIH/YBX3 is a pancancer immune-oncogenic system and could serve as a biomarker for diagnosis and prognosis and as a therapeutic target, especially in colon cancer.

Correlations between Intestinal Microbiota and Clinical Characteristics in Colorectal Adenoma/Carcinoma.

Background Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma. Aims To investigate the characteristics of intestinal microbiota in colorectal adenoma and carcinoma patients and the correlations with clinical characteristics. Methods Fecal samples were collected from 154 colorectal carcinoma patients (CRC group), 20 colorectal adenoma patients (AD group), and 199 healthy controls (control group). The intestinal microbiota was investigated by 16S rRNA gene sequencing. Results Compared to the healthy controls, microbial diversity was dramatically decreased in AD/CRC. At the genus level, Acidaminococcus significantly decreased with the order of control-AD-CRC (P < 0.05). Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. Combination of the top 10 most important species, including Butyricimonas synergistica, Agrobacterium larrymoorei, Bacteroides plebeius, Lachnospiraceae bacterium feline oral taxon 001, Clostridium scindens, Prevotella heparinolytica, bacterium LD2013, Streptococcus mutans, Lachnospiraceae bacterium 19gly4, and Eubacterium hallii, showed the best performance in distinguishing AD patients from CRC (AUC = 85.54%, 95% CI: 78.83%-92.25%). The clinicopathologic features, including age, sex, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC. Conclusion Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.