Tumor Node Metastasis Stage Research Articles

Identification of Survival Risk and Immune-Related Characteristics of Kidney Renal Clear Cell Carcinoma

Background Immunity exerts momentous functions in the progression and treatment of kidney renal clear cell carcinoma (KIRC). A better understanding of the relationship between KIRC and immunity may make a great contribution to evaluating the prognosis and immune-related therapeutic response of KIRC. Methods A series of information such as RNA sequence, clinical data, and tumor mutation burden (TMB) of KIRC patients were downloaded through The Cancer Genome Atlas (TCGA). Next, combining the survival information and gene expression data of TCGA and Gene Expression Omnibus (GEO), we established an immune gene-related prognosis model (IGRPM) and analyzed it. Then we constructed a nomogram which was convenient for clinicians to judge the prognosis of KIRC. Last but not the least, the expressions of some genes used to construct IGRPM in early KIRC, and adjacent normal tissues were verified through real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Perl (strawberry-perl-5.30.0.1-64bit), R software (4.0.3), and GraphPad Prism 7 were used to process the relevant data. Results The single-sample gene set enrichment analysis (ssGSEA) showed that there were significant differences in StromalScore, ImmuneScore, ESTIMATEScore, TumorPurity, 22 kinds of human immune cells infiltration, and HLA genes expression between high immunity group (Immunity_H) and low immunity group (Immunity_L). The Immunity_H expressed more immune-related genes and enriched more immune-related functions than the Immunity_L. In addition, compared with the low-risk group, the high-risk group had worse survival outcome and higher TMB. Combining IGRPM-based risk characteristic and TMB, we found that low-TMB + low-risk was the most beneficial to the survival outcome of KIRC patients. The risk characteristic based on IGRPM could be used as an independent prognostic factor for KIRC, and the nomogram constructed for evaluating the prognosis of KIRC showed excellent predictive potential. The RT-qPCR results suggested that not all the genes used to construct IGRPM showed differential expression in early KIRC compared with adjacent normal tissues, but all these genes had significant influence on the prognosis of KIRC. Conclusion These comprehensive immune assessments and survival predictions, integrating multiple aspects of data and clinical information, can provide additional value to the current Tumor Node Metastasis staging system for risk stratification of KIRC and may facilitate the development of KIRC immunotherapy.

Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer.

BackgroundCurrently, the prognosis of patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. This current study evaluated the relationship between histology of NSCLC and protein expression of exosomes in the plasma from NSCLC patients, and furthermore investigate the impact of the exosome profile on the tumor, node, metastasis (TNM) classification.MethodsPlasma samples were collected from 26 NSCLC patients before surgery. The exosomes were extracted from the plasma and liquid chromatography-mass spectrometry (LC/MS) was used to evaluate the expression of the proteins in the exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Cytoscape 3.8.2 software. Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to identify proteins which could effectively distinguish between lung adenocarcinoma and lung squamous cell carcinoma. The relationship between protein expression and the TNM stage was calculated using Spearman rank correlation.ResultsThe expression levels of ZSWIM9, FYB1, SERPINF1, C1orf68, MASP2, and IGHV3-72 were higher in patients with lung adenocarcinoma compared to patients with lung squamous cell carcinoma. MFGE8 was associated with the occurrence of squamous cell carcinoma. CORO1A was positively correlated with the TNM stage of the patients, and COL4A2 was negatively correlated with TNM stage. GO and KEGG analyses revealed that cholesterol metabolism was important in NSCLC development.ConclusionsLung adenocarcinoma may be distinguished from squamous cell carcinoma by the molecular profile of exosomes in the plasma samples. And, proteomics analysis suggested that cholesterol metabolism may play an important role of cancer progress in NSCLC.

Comparison of 6th, 7th, and 8th editions of the TNM staging in non-small cell lung cancer patients: Validation of the 8th edition of TNM staging.

Background In this study, we aimed to evaluate the effects of the transition from the 6th edition of the Tumor, Node, Metastasis (TNM) staging system to the 7th edition, and from the 7th edition to the 8th edition by comparing the stage migrations. We also aimed to externally validate the 8th edition of the TNM staging system. Methods Between September 2005 and June 2015, a total of 1,077 patients (986 males, 91 females; mean age: 59.6±8.3 years; range, 35 to 84 years) with non-small cell lung cancer who underwent lung resection were retrospectively analyzed. We re-staged patients according to 6th, 7th, and 8th TNM staging and compared the stage migrations of cases among the three staging systems. Results Stage migration in the transition to the 7th edition of the TNM staging system was observed in 368 (34.1%) patients whereas it was observed in 541 (50.2%) patients in the transition to the 8th edition (p<0.001). The rate of upstaging in transition to the 7th edition staging system was 50.2% (n=185), whereas it was 98.1% (n=531) for the transition to the 8th edition (p<0.001). The survival rates of Stages 1B, 2B and 3A increased with transition to the 7th edition and the survival rates of Stages 1B, 2A, 2B, 3A, and 3B increased with the transition to the 8th edition. The best stratification in the survival curves in the 6th edition was between 1B-1A and 3B-3A. In the 7th edition, it occurred between 1B-1A, 3A-2B and 3B-3A and, in the 8th edition, between 1B-1A and 3B-3A. Conclusion Stratification according to the 7th edition showed better prognostic validity compared to the 6th edition; and that of the 8th edition was better compared to the 7th edition.

Significance of platelet parameters in squamous cell carcinoma of oral cavity - A case-control study.

Tumor microenvironment plays an important role in cancer progression. Platelets are one of the components of the tumor environment shown to have a role in cancer survival and progression. Ninety-six cases of squamous cell carcinoma (SCC) cases of the oral cavity and 96 age/sex-matched healthy controls were considered for the study. Data regarding platelet count, platelet distribution width (PDW), mean platelet volume (MPV), Platelet-Large Cell Ratio (P-LCR), Plateletcrit (PCT), platelet/neutrophil ratio (PNR), platelet/lymphocyte ratio (PLR), and Platelet/Monocyte Ratio (PNR) from automated hematology analyzer records and clinicopathological data from the Department of Pathology were captured. These data were compared between cases and controls and also with tumor size, tumor grade, lymph node status, and tumour node metastasis (TNM) stage of cases. Mean ± standard deviation for platelet count, PDW, MPV, P-LCR, PCT, PNR, PLR and PMR among cases were 315.03 ± 98.26, 10.94 ± 1.66, 9.91 ± 0.77, 23.52 ± 5.64, 0.31 ± 0.086, 62.55 ± 31.51, 149.34 ± 61.32, and 498.67 ± 194.91, respectively, and among controls were 287.88 ± 74.11, 10.84 ± 1.18, 9.89 ± 0.72, 23.45 ± 4.55, 0.29 ± 0.061, 60.27 ± 21.02, 138.71 ± 49.28, and 497.64 ± 172.28, respectively. The association between means of platelet count, PDW, P-LCR, and PCT among cases and controls were statistically significant (P = 0.020, 0.006, 0.030, and 0.000, respectively). No statistically significant association was found between means of platelet count, PDW, MPV, P-LCR, PCT, PNR, PLR, and PMR versus tumor size, lymph node status, and tumor grades. The association between the means of PCT/PMR and TNM Stages I and II were statistically significant (P = 0.029 and 0.016, respectively). Platelet count, morphology, and functions are altered in oral SCC. Platelet activation plays an important role in oral cancer. PCT and PMR can be used to predict the progress of oral SCC as a cost-effective inflammatory marker.

EHD2 inhibits the invasive ability of lung adenocarcinoma and improves the prognosis of patients

BackgroundEH domain contains protein 2 (EHD2) may be involved in tumorigenesis and development. However, the role of EHD2 in lung adenocarcinoma (LUAD) is unknown.MethodsThe link between EHD2 and LUAD and the associated underlying mechanism was determined using bioinformatics analysis. Then, immunohistochemistry (IHC) was employed to detect EHD2 expression level in LUAD patients. The stable transfection cell line was used to establish with lentivirus vector, and then the transfection efficiency was detected by western blot. Phagokinetic motility assays, transwell assays, and western blotting were also employed to investigate EHD2 impacts on cell viability.ResultsThe results indicated that EHD2 protein expression in human LUAD samples was significantly lower than that in the adjacent normal tissues. Low EHD2 expression was significantly linked to lymph node metastasis as well as advanced tumor-node-metastasis (TNM) staging (P<0.05). The Kaplan-Meier survival curve showed that low EHD2 expression was significantly associated with low survival (P=0.01). The multivariate Cox regression analysis confirmed that EHD2 expression and TNM stage were independent prognostic factors for LUAD patients (all P<0.05). The in vitro experiments demonstrated that EHD2 knockdown markedly contributed to an increase in migration and invasion in A549 cells. Overexpression of EHD2 substantially suppressed H1299 cell migration and invasion. Furthermore, decreased E-cadherin expression was observed in A549 cells with EHD2 knockdown, as well as increased N-cadherin and vimentin expressions. By contrast, E-cadherin expression was increased in H1299 cells, whereas N-cadherin and vimentin expressions were decreased as a result of EHD2 overexpression.ConclusionsOur study demonstrated that EHD2 reduces LUAD migration and invasion by preventing the epithelial-mesenchymal transition (EMT) process. Furthermore, the results suggest that EHD2 may be a novel biomarker for prognosis prediction.

High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer.

Background: Gastric cancer (GC) has a high mortality rate and is particularly prevalent in China. The extracellular matrix protein, prolyl 4-hydroxylase subunit alpha 3 (P4HA3), has been implicated in various cancers. We aimed to assess the diagnostic and prognostic value of P4HA3 in GC and investigate its correlation with immune cell infiltration. Methods: The present study used microarray data from the Cancer Genome Atlas (TCGA) to analyze the association of P4HA3 expression with clinicopathological features. Data from the Gene Expression Omnibus (GEO) were used for validation. Receiver operating characteristic (ROC) and Kaplan–Meier curves were constructed to determine the diagnostic and prognostic value of P4HA3 in GC. Univariate and multivariate regression analyses were performed to assess the impact of P4HA3 on overall survival (OS) rates. A protein–protein interaction (PPI) network was generated and functional enrichment evaluated. Single-sample gene set enrichment analysis (ssGSEA) was conducted to correlate P4HA3 expression with immune cell infiltration. The correlation between P4HA3 and immune check point genes was studied. Results: P4HA3 was over-expressed in GC, along with 15 other types of cancer, including breast invasive carcinoma and cholangiocarcinoma. P4HA3 showed high diagnostic and prognostic value in GC and was an independent prognostic factor. P4HA3, TNM (tumor, node, metastases) stage, pathological stage and age all correlated with OS rates. Genes related to P4HA3 were enriched in the lumen of the endoplasmic reticulum and included procollagen-proline 3-dioxygenase activity. P4HA3 expression correlated with numbers of macrophages, natural killer (NK) cells, immature dendritic cells (iDC), mast cells, eosinophils, effective memory T cells (Tem), T-helper 1 (Th1) cells and dendritic cells (DC). P4HA3 was positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2) and programmed cell death 1 ligand 2 (PDCD1LG2). Conclusion: P4HA3 is a potential independent biomarker for prognosis of GC and may be an immunotherapy target in the treatment of GC.

Clinicopathological and prognostic role of ROC1 in neoplasms: A PRISMA-compliant systematic review and meta-analysis.

Background:Regulator of cullins 1 (ROC1) is frequently overexpressed in multiple tumors, and many pieces of research demonstrate that ROC1 is associated with the prognosis and development of a diversity of neoplasms and it is able to serve as a promising prognostic biomarker. Here we performed this meta-analysis to evaluate the prognostic and clinicopathological significance of ROC1 in patients suffering from cancer.Methods:We searched Pubmed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and WanFang database. The role of ROC1 in cancers was evaluated by pooled hazard ratios (HRs), odd ratios (ORs) and 95% confidence intervals (CIs).Results:In total, 9 studies including 1002 patients were enrolled in this analysis. The pooled results showed that patients with high expression of ROC1 had poor overall survival (OS) (HR: 2.04, 95% CI: 1.48–2.60, P < 0.001) and recurrence-free survival (RFS) (HR: 1.727, 95% CI: 0.965–2.488, P < 0.001). Additionally, elevated expression of ROC1 was significantly correlated with advanced clinical Tumor Node Metastasis stage (OR: 2.708, 95% CI: 1.856–3.951, P < 0.001), positive lymph node metastasis (OR: 1.968; 95% CI: 1.294–2.993, P = .002), large tumor size (OR: 1.522, 95% CI: 1.079–2.149, P = .017) and poor tumor differentiation (OR: 2.448, 95% CI: 1.793–3.344, P < 0.001).Conclusions:Elevated ROC1 expression predicted worse prognosis and advanced pathological parameters in various cancers. ROC1 was a significant prognostic biomarker for poor survival in human cancers.

Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections.

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.

Cell graph neural networks enable the precise prediction of patient survival in gastric cancer

Gastric cancer is one of the deadliest cancers worldwide. An accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the multiplexed immunohistochemistry (mIHC) images as Cell-Graphs, we propose a graph neural network-based approach, termed Cell−GraphSignatureorCGSignature, powered by artificial intelligence, for the digital staging of TME and precise prediction of patient survival in gastric cancer. In this study, patient survival prediction is formulated as either a binary (short-term and long-term) or ternary (short-term, medium-term, and long-term) classification task. Extensive benchmarking experiments demonstrate that the CGSignature achieves outstanding model performance, with Area Under the Receiver Operating Characteristic curve of 0.960 ± 0.01, and 0.771 ± 0.024 to 0.904 ± 0.012 for the binary- and ternary-classification, respectively. Moreover, Kaplan–Meier survival analysis indicates that the “digital grade” cancer staging produced by CGSignature provides a remarkable capability in discriminating both binary and ternary classes with statistical significance (P value < 0.0001), significantly outperforming the AJCC 8th edition Tumor Node Metastasis staging system. Using Cell-Graphs extracted from mIHC images, CGSignature improves the assessment of the link between the TME spatial patterns and patient prognosis. Our study suggests the feasibility and benefits of such an artificial intelligence-powered digital staging system in diagnostic pathology and precision oncology.

A dataset resource for clinically associated phosphosites in hepatocellular carcinoma.

Phosphorylation is one of the most common post-translational modifications (PTMs) and is closely related to protein activity and function, playing a critical role during cancer development. Quantitative phosphoproteomic strategies have been widely used to study the underlying mechanisms of cancer progression or drug resistance. In this report, we analyzed the association of phosphosite levels originated from our previously reported proteogenomic study in hepatocellular carcinoma (HCC) with clinical parameters, including prognosis, recurrence, and Tumor-Node-Metastasis (TNM) stages. By using both the log-rank test and univariate Cox proportional hazards regression analysis, we found that the abundance levels of 1712 phosphosites were associated with prognosis and those of 393 phosphosites associated with recurrence. Besides, 692 phosphosites had different abundance levels among TNM stages (I, II, III+IV) by Analysis of Variance (ANOVA) test. Gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using proteins with these statistically significant phosphosites. In conclusion, we provided a dataset resource for clinically associated phosphosites in HCC, which may be beneficial to liver cancer related basic research.

Polo-like kinase 4 is associated with advanced TNM stages and reduced survival and its inhibition improves chemosensitivity in colorectal cancer.

High expression of polo-like kinase 4 (PLK4) promotes tumorigenesis and is correlated with poor prognosis in several kinds of cancer. However, the prognostic value of PLK4 in colorectal cancer (CRC) has not been elucidated. The aim of the present study was to investigate the association between PLK4 and the prognosis and effect of PLK4 inhibition on chemosensitivity in CRC. A total of 142 patients with CRC were enrolled, and 142 pairs of CRC and para-carcinoma tissues were used to measure PLK4 protein expression using immunohistochemistry (IHC). Among them, 69 pairs were used to detect PLK4 mRNA expression using reverse transcription-quantitative PCR. In addition, PLK4-small interfering RNA (siRNA) was transfected into CRC cells, followed by 5-fluorouracil (5-FU) treatment for it was a fundamental chemotherapy for CRC. In addition, western blotting was used to detect PLK4 protein expression among human colonic epithelial cell and human CRC cell lines, including HCT-116, LoVo, SW480 and HT-29, as well as nuclear translocation of β-catenin. The IHC score and mRNA expression of PLK4 were higher in CRC tissues compared with para-carcinoma tissues (both P<0.001). Furthermore, the IHC score of tumor PLK4 was not correlated with pathological grade (P=0.585), T stage (P=0.357), N stage (P=0.107225) or tumor-node-metastasis (TNM) stage (P=0.093). The mRNA expression of tumor PLK4 was positively correlated with N stage (P=0.019) and TNM stage (P=0.004), but not with pathological grade (P=0.498) or T stage (P=0.112). Of note, the high protein expression of tumor PLK4 was an independent factor for poor overall survival (OS; P=0.048). In addition, PLK4 was elevated in CRC cell lines; PLK4-siRNA reduced the 50% inhibitory concentration value of 5-FU in HCT-116 (4.4±0.1 µM vs. 7.6±1.4 µM) and LoVo cells (5.5±0.6 µM vs. 9.9±1.8 µM) (both P<0.05). Besides, PLK4-siRNA decreased nuclear translocation of β-catenin. In conclusion, the high expression of tumor PLK4 was associated with advanced TNM stage and shorter OS in patients with CRC. In addition, targeting PLK4 improved chemosensitivity in CRC cells.

SENP1 Aberrance and Its Linkage to Clinical Features, Adjuvant Regimen, and Prognosis in Patients With Surgical Non-small Cell Lung Cancer Receiving Adjuvant Chemotherapy.

BackgroundSmall ubiquitin-like modifier-specific protease 1 (SENP1) plays vital roles in cancer progression and chemoresistance, but its prognostic value in non-small cell lung cancer (NSCLC) is vague. This study aimed to explore the correlation of SENP1 with clinical features, adjuvant chemotherapy regimen, and prognosis in patients with surgical NSCLC receiving adjuvant chemotherapy.MethodsTumor and adjacent tissues were collected from 157 patients with surgical NSCLC receiving adjuvant chemotherapy. Meanwhile, tumor tissue and paired adjacent tissue specimens were obtained to evaluate SENP1 protein expression by immunohistochemistry (IHC) assay; among which, 102 pairs were used to detect SENP1 messenger RNA (mRNA) by reverse transcription quantitative PCR.ResultsSENP1 IHC score and SENP1 mRNA expression were increased in tumor tissue than adjacent tissue (p < 0.001). Besides, elevated SENP1 IHC score was correlated with > 5 cm tumor size (p = 0.045), lymph node metastasis occurrence (p = 0.003), and advanced tumor-node-metastasis (TNM) stage (p = 0.012); meanwhile, increased SENP1 mRNA expression was associated with histopathological subtype (p = 0.011), lymph node metastasis occurrence (p = 0.008), and higher TNM stage (p = 0.015). Besides, no correlation was found in SENP1 IHC score (p = 0.424) or mRNA expression (p = 0.927) with specific adjuvant chemotherapy regimen. Additionally, both the SENP1 protein (high) (p = 0.003) and mRNA high (p = 0.028) were correlated with poor disease-free survival (DFS), while SENP1 protein high was also associated with shorter overall survival (OS) (p = 0.029). Furthermore, SENP1 protein (high vs. low) was independently associated with unsatisfying DFS [p = 0.009, hazard ratio (HR) = 1.798] and OS (p = 0.049, HR = 1.735).ConclusionSENP1 may serve as a potential biomarker to improve the management of patients with surgical NSCLC receiving adjuvant chemotherapy.

Abstract 5305: Delta-like ligand 3 immunohistochemical expression landscape in high-grade lung neuroendocrine tumors

Abstract Background: High-grade lung neuroendocrine tumors are a heterogeneous group of cancers with aggressive common features and a lack of effective therapeutic options. Recently, efforts have been made to identify new targets and drugs to improve clinical outcomes in these patients. Because of its high expression in neuroendocrine tumors compared to normal tissue, delta-like ligand 3 (DLL3) has emerged as a new therapeutic target in this setting.1,2 Targeting DLL3 with the half-life extended bispecific T cell engager (HLE BiTE®) immune therapy, tarlatamab, in a phase 1 clinical trial has demonstrated promising anti-tumor activity in small cell lung cancer (SCLC) patients.3 In order to more precisely guide patient selection and clinical trial design, a better understanding and quantification of DLL3 expression is required. Thus, we investigated DLL3 immunohistochemical expression across SCLC, large cell neuroendocrine carcinoma (LCNEC), and neuroendocrine carcinoma with combined histology (CNEC), and its associations with clinicopathological characteristics. Design: Formalin-fixed and paraffin-embedded surgically resected lung neuroendocrine carcinomas (SCLC, n=17; LCNEC, n=20; CNEC, n=8) were selected based on tissue availability at MD Anderson Cancer Center and stained with a commercially available immunohistochemistry assay for DLL3 (clone SP347, Ventana). Total percentage and intensity of DLL3 expression of neuroendocrine carcinoma cells were scored and the results were presented as H-Score (0-300) and percentage (%) of DLL3 positive tumor cells. We correlated DLL3 expression with clinicopathological characteristics. Results: DLL3 expression was observed in 37/45 (82%) of all cases (SCLC: %, median=65%, 0-100%; H-score, median=95, 0-175; LCNEC: %, median=65%, 0-100%; H-score, median=100, 0-180; CNEC: %, median=55%, 0-95%; H-score, median=90, 0-175). In patients with LCNEC, DLL3 % was higher in male patients (p=0.0500) and former smokers (p=0.0298) compared to females and current smokers, respectively. No other clinicopathological associations were found with age, Tumor-Node-Metastasis (TNM) staging system, recurrence, neoadjuvant therapy or overall survival. Conclusion:Our work confirms that most high-grade neuroendocrine tumors express DLL3 across histology types and TNM stage. Our results suggest that a large subset of patients with high-grade lung neuroendocrine tumors may be a target population of interest for DLL3-targeted therapies.

Abstract 1949: Circulating tumor cells presence shorten the cancer specific survival in colorectal cancer: 10 years follow-up study

Abstract Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide and metastases-related death is the main cause of its high mortality. Circulating/disseminated tumor cells (CTCs/DTCc) are considered as precursors of distant metastatic spread and can act as an independent prognostic biomarker. The impact of CTCs/DTCs presence in perioperative period on long-term cancer specific survival (CSS) was assessed. Patients and methods: The presence of CTCs/DTCs in peripheral blood, tumor-draining blood, and bone marrow of 188 colorectal cancer patients was analyzed before, immediately after, and one month after surgery using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to detect the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA-positive CTCs. The trial was registered at ClinicalTrials.gov (NCT 03337347), patients were followed-up and the cause of death was determined. Results: Over a median follow-up period of 116.5 months, 81 of 148 (54.7%) stage I-III CRC patients died. In total, 40.7% of them (33/81) died of cancer. The presence of CTCs/DTCs did not correlate with any conventional clinical or pathological features (tumor node metastasis (TNM) stage, grade, KRAS mutations or microsatellite instability). Patients with CTCs/DTCs in the peripheral blood and bone marrow one month after surgery had significantly shorter CSS (p=0.013, HR=2.6; resp. p=0.019, HR=2.3) than those without CTCs/DTCs. Shorter overall survival was also observed in patients with tumor-draining blood CEA mRNA-positive CTCs before surgery (p=0.014). Conclusion: The presence of CK20 mRNA-positive CTCs/DTCs in blood and bone marrow after surgery was confirmed as an independent negative prognostic factor for the long-term cancer-specific survival in stage I-III colorectal cancer patients.The study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132; LM2018133), Palacky University Olomouc (LF 2021_019) and European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868, ACGT CZ.02.1.01/0.0/0.0/16_026/0008448). Citation Format: Josef Srovnal, Pavel Skalicky, Alona Rehulkova, Kamil Vyslouzil, Monika Vidlarova, Jana Vrbkova, Marian Hajduch. Circulating tumor cells presence shorten the cancer specific survival in colorectal cancer: 10 years follow-up study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1949.

Construction of a Six-Gene Prognostic Risk Model Related to Hypoxia and Angiogenesis for Cervical Cancer.

Background: The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model. Methods: Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. Results: Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes (MOCSI, PPP1R14A, ESM1, DES, ITGA5, and SERPINF1). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, p < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores. Conclusions: We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.

Lymphovascular invasion: A non-sized T descriptor for stage IA non-small cell lung cancer.

BackgroundLymphovascular invasion (LVI) has not been included in the tumor‐node‐metastasis (TNM) staging manual of non‐small‐cell lung cancer (NSCLC). We aimed to investigate the predictive value of LVI on stage IA NSCLC and proposed a method of incorporating LVI into the T category based on the latest TNM staging manual.MethodsThe least absolute shrinkage and selection operator (LASSO)‐penalized Cox multivariable regression model was performed to identify prognostic factors. The Kaplan–Meier method was used to compare overall survival (OS) and disease‐free survival (DFS) between groups. Propensity score matching (PSM) was used to minimize bias.ResultsA total of 1452 eligible stage I NSCLC cases (stage IA without LVI, 1022 cases; stage IA with LVI, 120 cases; stage IB, 310 cases) were included. LASSO‐penalized multivariable Cox analysis revealed that LVI was an independent prognostic factor for both OS and DFS. Survival analysis demonstrated that the survivals of stage IA NSCLCs without LVI were better than those of stage IA with LVI and stage IB NSCLCs. In the matched cohort, the survivals of stage IA NSCLCs with LVI were comparable to those of stage IB NSCLCs.ConclusionsStage IA NSCLCs with LVI and stage IB NSCLCs had similar survivals, and we proposed that LVI might be a non‐sized T descriptor that upstaged stage IA diseases to stage IB.

Peking Prognostic Score, Based on Preoperative Sarcopenia Status, Is a Novel Prognostic Factor in Patients With Gastric Cancer.

BackgroundThis study focused on assessing the role of the Peking prognostic score (PPS), a novel prognostic index based on muscle atrophy and lymphocyte-to-C-reactive protein ratio, within gastric cancer patient prognosis.MethodsWe analyzed the data collected from 774 gastric cancer cases between April 2011 and February 2016 (discovery cohort). The results were assessed in 575 gastric cancer cases from March 2016 to September 2019 (validation cohort). For evaluating skeletal muscle mass, we obtained computed tomography images at the third lumbar vertebra level (L3). We performed a time-dependent receiver operating characteristic curve (t-ROC) to analyze PPS’s prognostic significance with others.ResultsThe discovery cohort enrolled altogether 774 patients with non-metastatic gastric cancer, including 639 (82.5%) men along with 135 (17.5%) women. The patients were divided into 3 groups; 166 patients (21.4%) were assigned into group 0, 472 (60.9%) in group 1, and 136 (17.7%) in group 2, respectively. An increased PPS was in direct proportion to an elder age, reduced body mass index, higher Pathological Tumor Lymph Node Metastasis stage, perineural invasion, and vascular invasion. We identified PPS to independently estimate patient overall survival (OS) together with disease-free survival (DFS; both P < 0.001). Additionally, as revealed by t-ROC analysis, PPS exhibited the highest sensitivity compared with other prognostic scoring systems in predicting patient survival. Finally, we evaluated the prognostic value of PPS in the validation cohort and confirmed that preoperative PPS independently estimates patient OS and DFS.ConclusionThe PPS accounts for an efficient nutrition-inflammation prognostic scoring system in gastric cancer patients.

Does pretreatment elevated calcitonin level cause the poor prognosis in patients with medullary thyroid cancer?

BackgroundMedullary thyroid carcinoma (MTC) patients have poor survival, tumor/node/metastasis (TNM) stage and biochemical prognosis are the most important factors. We investigated the clinical significance of calcitonin (Ctn) to assess the biochemical prognosis of MTC.MethodsThis retrospective observational study enrolled 77 MTC patients with complete information and primary surgery at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University between 2009 and 2020. Patient and MTC characteristics were recorded. All patients were divided into remission, stable, and progression according to biochemical prognosis. We analyzed the correlation between preoperative serum Ctn, TNM stage and biochemical prognosis.ResultsElevated preoperative serum Ctn was positively correlated with TNM stage. Patients with higher Ctn, multifocality, and bilateral tumors were associated with a higher TNM stage. Multivariate logistic regression analysis showed that preoperative serum Ctn level was an independent risk factor for TNM stage. Receiver operating characteristic (ROC) analysis found the best Ctn cut-off value for predicting TNM III was 45.88 pg/mL, which had a sensitivity of 87.2% and a specificity of 65.8%. The best Ctn cut-off value for predicting TNM IV was 167.00 pg/mL, with a sensitivity of 92.9% and a specificity of 77.6%. In univariate analysis, patients with higher preoperative serum Ctn, multifocality, bilateral tumors, and higher TNM stage were more likely to progress. The optimal cut-off value for progression was 195.5 pg/mL, which had a sensitivity of 80.0% and a specificity of 70.2%. For every 1-unit increase in preoperative serum Ctn levels, the risk of progression increased by 1.004 times (P=0.008), and patients with TNM stage III [hazard ratio (HR) =9.663; 95% confidence interval (CI): 1.411, 66.156] were nearly 9.7-fold more likely to progress than those in TNM stage I/II.ConclusionsElevated preoperative serum Ctn predicted poor clinical outcomes in MTC.

The Prognostic Value of Long Non-Coding RNA SNHG7 in Human Cancer: A Meta-Analysis.

The long non-coding RNA SNHG7 is upregulated in many types of cancer and plays a role as an oncogene. However, its overall predictive ability in human cancer prognosis has not been assessed using existing databases. Therefore, further study of its prognostic value and clinical significance in human malignancies is warranted. We systematically collected relevant literature from multiple electronic document databases about the relationship between SNHG7 expression level and prognosis in patients with solid cancers. We further screenped them for eligibility. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the prognostic value. Odds ratios (ORs) and their 95% CIs were collected to evaluate the relationship between the expression of SNHG7 and clinicopathological features, including lymph node metastasis (LNM), tumour size, tumour node metastasis (TNM) stage and histological grade. Fourteen original studies involving 971 patients were enrolled strictly following the inclusion and exclusion criteria. The meta-analysis showed that SNHG7 expression significantly correlated with poor overall survival (HR = 1.93, 95% CI: 1.64-2.26, p<0.001) in human cancer patients. In addition, the pooled OR indicated that overexpression of SNHG7 was associated with earlier LNM (OR = 1.83, 95% CI: 1.44-2.32; P <0.001), and advanced TNM stage (OR = 1.82, 95% CI: 1.44-2.30; P <0.001). Meanwhile, there was no significant heterogeneity between the selected studies, proving the reliability of the meta-analysis results. High SNHG7 expression may predict poor oncological outcomes in patients with multiple human cancers, which could be a novel prognostic biomarker of unfulfilled clinicopathological features. However, further high-quality studies are needed to verify and strengthen the clinical value of SNHG7 in different types of cancer.

The efficacy and safety of continuous intra-arterial infusion neoadjuvant chemotherapy with surgery for locally advanced gastric cancer: a preliminary pilot study.

Neoadjuvant chemotherapy (NAC) followed by R0 resection is regarded as a standard treatment strategy for locally advanced gastric cancer (GC); however, the response to systemic chemotherapy remains unsatisfactory. Continuous intra-arterial infusion chemotherapy (CAIC) is a new method, compared with systematic chemotherapy, it can deliver chemotherapy drugs more accurately, so as to achieve higher surgical conversion rate. This study aimed to explore the efficacy and safety of CAIC in locally advanced GC patients. In this retrospective pilot study, four patients with histologically confirmed locally advanced GC were identified from a tertiary hospital between May 2018 and December 2018. Clinic stage was belonged to T4N1-3M0 in all cases with potential probability for surgery. All cases received three cycles of NAC by CAIC with oxaliplatin (100 mg on day 1) plus oral S-1 (80 mg/m2/day twice daily for 14 days) (SOX). Contrast-enhanced computed tomography (CT) scans and pathological examinations were performed to evaluate chemotherapeutic response based on the tumor regression grade (TRG) and post-neoadjuvant pathological Tumor Node Metastasis (ypTNM) staging. All cases were regularly followed up with face-to-face interviews at outpatient, abdominal enhanced CT scan and serum tumor markers were be requested at 3-month intervals for up to 1 year postoperatively. The obstruction was significantly alleviated after three cycles of CAIC. Contrast-enhanced CT scans showed decreased tumor volume to some extent, along with lymph node shrinkage after treatment. Radical (R0) resection was achieved in all cases. Histopathological analysis showed tumor downstaging in three cases and upstaging in one case. The tumor response to treatment demonstrated TRG1a in one case, TRG1b in one case, and TRG2 in two cases, with an overall tumor regression rate of 100%. No obvious adverse events or perioperative complications were observed during or following treatment. All cases were alive without tumor recurrence or progression after the 1-year postoperative follow-up. Our study may shed light on super-selective CAIC as an effective method for improving the NAC response in locally advanced GC. Future studies with a larger sample sizes and long-term outcomes are required for a final conclusion.