Examining nonlinear effects of socioecological drivers on urban solar energy development in China using machine learning and high-dimensional data.

In the context of carbon neutrality target, renewable energy sources have been transforming from "supplementary energy" to "main energy", which have promoted the green and low-carbon transition of global energy supply system. In-depth analyzing the spatial patterns and driving mechanisms of renewable energy expansion are of significance for optimizing the spatial layout of clean power, and avoiding the phenomenon of wind and solar power curtailment. In this paper, we proposed an ensemble learning model to examine the nonlinear effects of physical geography, resource endowment, and socio-economic factors on solar photovoltaic (PV) capacity at the prefecture-level city scale in China. Using the city-level multi-sources geospatial big data, we extensively collected a total of 175 related explanatory variables and cumulative installed capacity of solar PV power for 295 prefecture-level cities of China. The recursive feature elimination algorithm (SVM-REF) is firstly used to extract the optimal feature subset of urban PV capacity from multi-dimensional features variables. Furthermore, three advanced machine learning models (random forest, decision tree, extreme gradient boosting) are developed to identify the key influencing factors and nonlinear driving effect of urban solar PV power expansion in China. The results show that China's PV installation capacity is highly concentrated in Northern and Northwest parts of China, with the occupancy over 70% in 2019. Moreover, the XGBoost model has the best prediction accuracy (R2 = 0.97) among three methods. We also found that total amount of urban water resources, average solar radiation, and population density are the most important controlling factors for urban solar PV capacity expansion in China, with contribution of 35.6%, 17.7%, and 13.3%, respectively. We suggested that urban solar PV layout mode in China is recommended to gradually shift from resource orientation to the "resource-environment-demand" comprehensive orientation. The paper provides a replicable, scalable machine learning models for simulating solar PV power capacity at the prefecture-level city scale, and serves as a motivation for decision-making reference of the macro siting optimization and sustainable development of China's green power industry.

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next-generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C-KIT mutations were the most common targets of highest-level actionable alterations. In DNA mismatch repair-proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild-type/nondisruptive mutations (KRASmut /TP53wt/non-dis ) were independently associated with an inferior recurrence-free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94-9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.

Factors Affecting the Outcomes of Patients with Malignant Rhabdoid Tumors: A Population-Based Study.

Objective: Malignant rhabdoid tumor (MRT) is a rare but aggressive malignancy. It has been a long time since data on this tumor have been updated. Methods: We retrospectively reviewed patients from the SEER database who were pathologically diagnosed with MRT and analyzed incidence rates, clinical features and survival using Stata 12.0. Results: In total, 544 patients were included in the epidemiological analysis. There were two peak periods of MRT incidence: patients younger than 4 years and those older than 70 years. Further survival analysis showed that the survival of children (especially younger than 1 year) was markedly worse than that of adults (P<0.01), and different primary sites were associated with different age groups and survival outcomes. The central nervous system (CNS) was the most common primary site (50.00%), followed by the kidney (15.66%). Patients with MRTs that originated from the digestive system experienced worse survival outcomes than those with MRTs originating from other locations. Primary site surgery conferred survival benefits to patients with renal and digestive system MRTs (HR = 0.06, CI: 0.02-0.23, P<0.01; HR=0.10, CI: 0.02-0.48, P<0.01), whereas radiotherapy conferred benefits to patients with CNS, bone and soft tissue MRTs (HR=0.22, CI: 0.15-0.34, P<0.01; HR=0.44, CI: 0.21-0.90 P=0.03). Conclusions: Our results indicate that age and the primary site of MRT are critical clinical factors that affect patient survival and treatment choices. Primary site tumor resection should be considered for renal and digestive system MRTs, and systematic therapy, including surgery and radiotherapy, should be recommended for the treatment of CNS, bone and soft tissue MRTs.

Pan-cancer analyses demonstrate that ANKRD6 is associated with a poor prognosis and correlates with M2 macrophage infiltration in colon cancer.

OBJECTIVE: Ankyrin repeat domain-containing protein 6 (ANKRD6) is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego. However, the correlations between ANKRD6 and tumor-infiltrating immune cells in cancers is not clear. METHODS: ANKRD6 expression was analyzed by Oncomine, Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). PrognoScan and GEPIA were used to evaluate the influence of ANKRD6 on clinical prognosis. TIMER and CIBERSORT were used to analyze correlations between ANKRD6 expression levels and tumor immune cell infiltrates. Immunohistochemical analysis of the relationship between ANKRD6 expression and overall survival, as well as the relationship between ANKRD6 expression and M2 macrophage infiltration, was performed. RESULTS: High level of ANKRD6 expression was associated with poor prognosis of colon cancer. ANKRD6 expression level was positively correlated with infiltrating levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in colon cancer by using TIMER. Using CIBERSORT, we found that in plasma cells, CD8+ T cells, CD4+ memory resting T cells, follicular helper T cells and activated natural killer cells were significantly lower in the ANKRD6-high group than in the ANKRD6-low group. M0 and M2 macrophages were significantly higher in the ANKRD6-high group than in the ANKRD6-low group. Immunohistochemistry confirmed that M2 macrophage infiltration in the ANKRD6-high group significantly increased. CONCLUSIONS: The high ANKRD6 expression is associated with poor prognosis of colon cancer. ANKRD6 expression is positively correlated with M2 macrophage infiltration in colon cancer.

High-risk Stage III colon cancer patients identified by a novel five-gene mutational signature are characterized by upregulation of IL-23A and gut bacterial translocation of the tumor microenvironment.

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the five-gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.

Diverse fragment lengths dismiss size selection for serum cell-free DNA: a comparative study of serum and plasma samples.

Background: The objective of this study was to determine the features of fragment length for circulating cell-free DNA (cfDNA) from plasma and serum samples. Methods: Plasma and serum samples from different sources were randomly collected. Circulating cfDNA was extracted and purified by a precipitation-enriched and spin-column-based kit. The concentration of the purified DNA was immediately measured by a highly sensitive dsDNA quantitative assay, and then the fragment length was analyzed by capillary electrophoresis. The abundance of a specific fragment was estimated by the area under curve (AUC) for the fragment peak in the capillary electrophoresis. Results: A total of 199 plasma and 117 serum samples were extracted and analyzed. The average yield of cfDNA from the serum samples (131.67 ng/mL) was significantly higher than that from the plasma samples (32.78 ng/mL, p < 0.001). The average abundance of the 20-400 bp fragments in plasma cfDNA (84.4%) was significantly higher than that of serum cfDNA (51.9%, p < 0.001). Fragment peaks in serum cfDNA always presented in regions around 190 bp, 430 bp, and 630 bp, but plasma cfDNA generally showed a sharp peak in the 165-190 bp region and a much lower peak in the 300

Deciphering molecular properties of hypermutated gastrointestinal cancer.

Great mutational heterogeneity is observed both across cancer types (>1000-fold) and within a given cancer type, with a fraction harboring >10 mutations per million bases, thus termed hypermutation. We determined the genome-wide effects of high mutation load on the transcriptome and methylome of two cancer types; namely, colorectal cancer (CRC) and stomach adenocarcinoma (STAD). Briefly, hierarchical clustering of the expression and methylation profiles showed that the majority of CRC and STAD hypermutated samples were mixed and separated from their respective non-hypermutated samples, exceeding the boundary of tissue specificity. Further in-detailed exploration uncovered that the underlying molecular mechanism may be related to the perturbation of chromatin remodeling genes.

Analysis and inspection techniques for mouse liver injury based on terahertz spectroscopy.

At present, researchers are exploring biological tissue detection method using terahertz techniques. In this paper, techniques to inspect mouse liver injury by using terahertz spectroscopy were studied. The boxplots were applied to remove abnormal data, and the maximal information coefficient was employed to select crucial features from the absorption coefficient and refractive index spectra. Random Forests and AdaBoost were applied to recognize different levels of liver injury. We found that AdaBoost had better performance on low-level injury classification. This work suggests that terahertz techniques have the potential to detect liver injury at an early stage and evaluate liver treatment strategies.

Subtyping of microsatellite instability-high colorectal cancer.

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis than patients with microsatellite stable (MSS) CRC. However, some MSI-H CRC patients do not gain overall survival benefits from immune checkpoint-blockade treatment. In other words, heterogeneity within the subgroup of MSI-H tumors remains poorly understood. Thus, an in-depth molecular characterization of MSI-H tumors is urgently required. METHODS: Here, we use nonnegative matrix factorization (NMF)-based consensus clustering to define CRC MSI-H subtypes in The Cancer Genome Atlas and a French multicenter cohort GSE39582. CIBERSORT was used to calculate the proportions of 22 lymphocytes in tumor tissue in MSI-H subtypes. RESULTS: MSI-H CRC samples basically clustered into two subgroups (MSI-H1 and MSI-H2). MSI-H1 was characterized by a lower BRAF mutational status, higher frequency of chromosomal instability, global hypomethylation, and worse survival than MSI-H2. Further examination of the immune landscape showed that macrophages of the M2 phenotype were enriched in MSI-H1, which may be associated with poor prognosis in this subgroup. CONCLUSIONS: Our results illustrate the genetic heterogeneity in MSI-H CRCs and macrophages may serve as good targets for anticancer therapy in MSI-H1.

SPARCL1, a Novel Prognostic Predictive Factor for GI Malignancies: a Meta-Analysis.

BACKGROUND/AIMS: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is abnormally expressed in gastrointestinal (GI) malignancies. However, the correlation between SPARCL1 expression and the prognosis of patients remains unknown. Therefore, we performed a meta-analysis to investigate the potential value of SPARCL1 as a prognostic predictive marker for GI malignancies. METHODS: The PubMed, Embase, EBSCO, CNKI, and Wanfang databases were systematically searched for studies examining SPARCL1 and clinicopathological features, including the prognoses of patients. Hazard ratios (HRs) and odds ratios (ORs) from individual studies were calculated and pooled using a random-effects or fix-effects model. Heterogeneity and publication bias analyses were performed. RESULTS: Data from 8 studies, including a total of 2,356 patients, were summarized. The expression of SPARCL1 suggested a better prognosis (HR=0.57, 95% CI: 0.445-0.698, P=0.000) and was associated with clinicopathological features of GI malignancies, including distant metastasis (OR=0.44, 95% CI: 0.23-0.85, P=0.014), lymph node metastasis (OR=0.56, 95% CI: 0.39-0.81, P=0.002) and tumor differentiation (OR=2.21, 95% CI: 1.82-2.69, P=0.000). Subgroup analyses based on cancer type revealed that the expression of SPARCL1 had no effect on lymph node metastasis in colorectal cancer, and it did not influence tumor differentiation in gastric cancer. Egger's test showed no evidence of publication bias (all P>0.05). CONCLUSION: SPARCL1 could be a novel prognostic predictive factor for GI malignancies. The expression of SPARCL1 could influence the clinicopathological features of GI malignancies. Further large-scale studies are essential to confirm SPARCL1's prognostic predictive value, and more fundamental experimental studies are needed to illustrate the mechanisms.

Serum profiling by mass spectrometry combined with bioinformatics for the biomarkers discovery in diffuse large B-cell lymphoma.

The aim of this study was to identify potential serum biomarkers of diffuse large B-cell lymphoma (DLBCL) and to detect DLBCL therapy response biomarkers. DLBCL serum proteomic analysis was performed using the CM10 ProteinChip mass spectrometry (SELDI-TOF-MS) approach combined with bioinformatics. A total of 178 samples were analyzed in this study from untreated early stage DLBCL patients (38), patients with inflammatory lymphadenopathy (13), healthy donors (35), post-treatment non-relapsed DLBCL patients (53), and relapsed DLBCL patients (39). Model 1 formed by nine protein peaks (m/z: 6443, 5913, 6198, 4098, 7775, 9293, 5946, 5977, and 4628) could be used to distinguish DLBCL patients from healthy individuals with an accuracy of 95.89% (70/73). The diagnostic pattern constructed using the support vector machine including the nine proteins of model 1, showed a maximum Youden's Index. Model 2 formed by three protein peaks (m/z: 3942, 6639, and 4121) could be used to distinguish DLBCL patients from those with inflammatory lymphadenopathy with an accuracy of 94.12% (48/51). Model 3 formed by six protein peaks could distinguish patients with inflammatory lymphadenopathy from healthy individuals with an accuracy of 97.92% (47/48). Model 4 could be used to distinguish non-relapsed DLBCL patients from relapsed DLBCL patients with an accuracy of 84.78% (78/92). The four patterns were validated by leave-one-out cross-validation. These data demonstrate that the CM10 ProteinChip and SELDI-TOF-MS approach combined with bioinformatics can be used effectively to screen for the differential protein expression profiles of DLBCL patients and to predict the response to therapy.

High expression of SHP2 predicts a promising prognosis in colorectal cancer.

Background: Src homology 2 domain-containing phosphatase 2 (SHP2) is hyper-activated in some solid tumors. Previous findings suggest that the expression of SHP2 in colorectal cancer (CRC) may be associated with prognosis. However, validation with large sample data is lacking. Materials and Methods: Tissue microarrays containing 860 CRCs and 197 mucosal tissues adjacent to the tumors were constructed. Immunohistochemistry was used to evaluate the expression of SHP2. Differences between SHP2 expression and clinicopathological parameters were evaluated. Kaplan-Meier survival curves and log-rank tests were used to analyze the relationships between SHP2 expression and the overall survival of patients. A Cox proportional hazard regression model was used for univariate and multivariate analyses of prognostic factors. Results: SHP2 expression in CRCs tissues was significantly higher than those in adjacent mucosal tissues (P < 0.001). SHP2 expression was related to tumor differentiation, depth of invasion, distant metastasis, vascular tumor thrombus, lymph node metastasis, and TNM classification (P < 0.05). The prognosis of the high-expression group of SHP2 was significantly better than that of the low-expression group (P = 0.008). Univariate analysis showed that the expression of SHP2 was a prognostic factor for CRC (P = 0.008). Multivariate analysis demonstrated that SHP2 remained an independent prognostic factor for CRC (P = 0.033). Conclusion: The expression of SHP2 was significantly higher in CRC tissues than in adjacent normal tissues. High expression of SHP2 was associated with a promising outcome, suggesting that SHP2 may be a favorable prognostic indicator of CRC.

Diagnostic inconsistency of faecal immunochemical tests for haemoglobin in population screening of colorectal cancer.

BACKGROUND: There is currently very little data available on the consistency of quantitative and qualitative faecal immunochemical test (FIT) for colorectal cancer screening. METHODS: A representative random population (n=1889, 40-74 year olds) in Jiashan, China was invited for FIT screening in 2012. Faecal samples were collected by a single specimen collection device and simultaneously tested by a quantitative FIT (OC-SENSOR, OC) and two qualitative FITs (FIT A and FIT B with intrinsic positive haemoglobin cut-off concentrations of 20 µg Hb/g faeces and 40 µg Hb/g faeces, respectively). The observational criteria for a positive result of the qualitative FIT were set according to the density of the colour appearing in the test strip. The results produced by the quantitative and qualitative FIT for each sample were compared. κ coefficient was used to measure consistency. RESULTS: A total of 1368 (72.4%) individuals returned faecal samples. Both FIT A and FIT B precisely identified all faecal samples with haemoglobin concentration above 100 µg Hb/g faeces, but the overall consistency was poor for OC & FIT A (κ=0.32, 95% CI 0.20-0.44) and was moderate for OC & FIT B (κ=0.74, 95% CI 0.64-0.85). A more favourable consistency (κ=0.64, 95% CI 0.57-0.72) was achieved when a different positive criterion was employed for FIT A. CONCLUSIONS: The diagnostic inconsistency between quantitative and qualitative FITs mainly exists in the faecal samples with low haemoglobin concentrations. Refining the criterion for a positive result may be a feasible way to improve the accuracy of qualitative FIT.

The high expression of FOXE1 in colorectal cancer predicts a promising prognosis: a retrospective study.

Purpose Forkhead box (FOX) family proteins regulate transcription and DNA repair and are involved in cell growth, differentiation, embryogenesis, and lifespan. The transcription factor FOXE1 is a member of the FOX family. The relationship between the expression level of FOXE1 and colorectal cancer (CRC) prognosis remains controversial. It is vital to verify the relationship between FOXE1 expression and the prognosis of patients with CRC. Methods We constructed a tissue microarray containing 879 primary colorectal cancer tissues and 203 normal mucosa samples. The tumor and normal mucosa tissues were stained with FOXE1 by immunohistochemistry, and the staining results were divided into two groups: high expression group and low expression group. Chi-square test was performed for the classification variable of the difference between FOXE1 expression levels and clinicopathological parameters. The survival curve was calculated according to the Kaplan-Meier method and the logarithmic rank test. The Cox proportional risk regression model was used for multivariate analysis of prognostic factors in patients with CRC.Results The expression level of FOXE1 in colorectal cancer was higher than that in the normal mucosa adjacent to cancer, although the difference was not significant. However, the expression of FOXE1 was correlated with tumor size, T stage, N stage, M stage, and pTNM stage. Univariate and multivariate analyses suggested that FOXE1 could be used as an independent prognostic factor in patients with CRC. Conclusions FOXE1 may be a potential independent prognostic factor for colorectal cancer patients.

Gene expression profile of human colorectal cancer identified NKTR as a biomarker for liver metastasis.

OBJECTIVE: Liver metastasis is one of the prognostic factors of colorectal cancer (CRC). The aim of this study is to identify biomarkers that facilitate easier detection of liver metastasis. METHODS: Significance Analysis of Microarrays (SAM) and Array Data Analyzer (ADA) were applied used for the analysis of differentially differently expressed mRNAs. mRNA expression was verified by quantitative real-timer reverse transcriptiontase polymerase chain reaction (qRT-PCR). Immunohistochemistry were was used to show natural killer-tumor recognition (NKTR) expression in CRC. NKTR-knockdown CRC cells were constructed obtained by using short hairpin RNA (shRNA). Followed by CCK-8 assay, plate colony formation test, and transwell assay were used to evaluate the influence of NKTR on cell proliferation, migration, and invasion in vitro. RESULTS: SAM yielded showed 256 up-regulated and 224 down-regulated differentially differently expressed genes. Seven genes were identified by using ADA, tools and four genes were verified by using qRT-PCR. Three genes (metastasis associated lung adenocarcinoma transcript 1 (MALAT1), nuclear factor I/B (NKTR), and nuclear factor I/B (NFIB)) showed a statistically significant considerabley difference between CRC with and liver metastasis and CRC without liver metastasis. Immunohistochemical analysis showed that NKTR expression was much lower in primary CRC with liver metastasis than that in primary CRC without liver metastasis. The NKTR protein plays a role in the lytic function of natural killer (NK) cells and it has been rarely studied in the CRC. The down-regulation of NKTR by shRNA interference in CRC cells increased cell proliferation, migration, and invasion in vitro.

Comprehensive Analysis of Genomic Alterations in Hepatoid Adenocarcinoma of the Stomach and Identification of Clinically Actionable Alterations.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignancy with aggressive biological behavior. This study aimed to compare the genetic landscape of HAS with liver hepatocellular carcinoma (LIHC), gastric cancer (GC), and AFP-producing GC (AFPGC) and identify clinically actionable alterations. Thirty-eight cases of HAS were collected for whole-exome sequencing. Significantly mutated genes were identified. TP53 was the most frequently mutated gene (66%). Hypoxia, TNF-α/NFκB, mitotic spindle assembly, DNA repair, and p53 signaling pathways mutated frequently. Mutagenesis mechanisms in HAS were associated with spontaneous or enzymatic deamination of 5-methylcytosine to thymine and defective homologous recombination-related DNA damage repair. However, LIHC was characteristic of exposure to aflatoxin and aristolochic acid. The copy number variants (CNVs) in HAS was significantly different compared to LIHC, GC, and AFPGC. Aggressive behavior-related CNVs were identified, including local vascular invasion, advanced stages, and adverse prognosis. In 55.26% of HAS patients there existed at least one clinically actionable alteration, including ERBB2, FGFR1, CDK4, EGFR, MET, and MDM2 amplifications and BRCA1/2 mutations. MDM2 amplification with functional TP53 was detected in 5% of HAS patients, which was proved sensitive to MDM2 inhibitors. A total of 10.53% of HAS patients harbored TMB > 10 muts/Mb. These findings improve our understanding of the genomic features of HAS and provide potential therapeutic targets.

Primary tumor location (right versus left side of the colon) and resection affect the survival of patients with liver metastases from colonic neuroendocrine carcinoma: a population-based study.

BACKGROUND: Colonic neuroendocrine carcinomas (co-NECs) are heterogeneous and aggressive, especially with regard to metastasis. Whether co-NECs on the right and left sides of the colon have different characteristics from colon adenocarcinoma is unknown. METHODS: The co-NEC patients were selected from the 2010-2017 Surveillance, Epidemiology, and End Results Program (SEER) database. The right and left sides of the colon were separated by the splenic flexure. Coarsened exact matching (CEM) was performed to adjust for relevant factors before regression models were constructed. RESULTS: A total of 669 pathologically diagnosed co-NEC patients with sufficient baseline data were identified from the SEER database. A total of 80.72% of the patients had co-NEC that originated from the right side of the colon, and their mean overall survival (mOS) was similar to that of the patients with left-sided co-NECs (right versus left: 22.30 m versus 22.55 m). A total of 44.84% of the patients were diagnosed with liver metastasis (46.68% right side versus 37.98% left side). In patients with liver metastasis, those with right-sided co-NECs had better survival than those with left-sided co-NECs (mOS right versus left: 15.37 m versus 9.62 m; adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI): 0.49-0.98, p = 0.035). To further investigate the survival benefits of primary site resection, we separated the patients who had liver metastasis according to the primary site and performed CEM to balance the groups (no patients underwent liver metastasis resection or intervention). The results suggested that primary surgery could benefit patients with both left- and right-sided co-NECs (adjusted HR = 0.50, 95% CI: 0.33-0.77, p = 0.001 on the right side; HR = 0.38, 95% CI: 0.16-0.89, p = 0.026 on the left side). CONCLUSIONS: Co-NECs frequently originate on the right side and commonly develop liver metastasis. Right-sided co-NECs are associated with better survival than left-sided co-NECs after liver metastasis has occurred. Primary site resection is associated with prolonged survival in co-NEC patients with liver metastasis, regardless of the side from which the co-NEC has originated.

Hypermutated tumours across 11 cancer types show three distinct immune subtypes.

BACKGROUND: Complete remission is observed in less than half of hypermutated (HM) tumours after immune checkpoint blockade therapy, indicating that HM tumours are very heterogeneous. Thus, there is an urgent requirement to decipher the unknown intrinsic HM tumour subtypes. METHODS: Statistical analysis was performed on somatic mutation data from 5519 tumours across 11 cancer types obtained from The Cancer Genome Atlas and 338 colorectal cancer (CRC) samples obtained from an Asian cohort. Samples with a tumour mutation burden >10 mut/Mb were classified as HM. A total of 1040 HM samples harbouring corresponding transcriptomes were used for non-negative matrix factorisation clustering. Tumour mutational burden, neoantigens, T cell receptor (TCR) diversity, stromal score and immune score were compared between the subtypes. RESULTS: HM tumours fell into three distinct immune subtypes: HM1, HM2 and HM3. HM3 tumours were correlated with increased CD8 T cell infiltration, high TCR diversity, a high immune score and prolonged survival. HM2 tumours were correlated with an abundant stromal component, epithelial-mesenchymal transition, TGFß, angiogenesis hallmarks and poor outcomes. The infiltration of more CD8 T cells and increased chemokine expression in HM3 were validated in CRC by immunofluorescence. CONCLUSIONS: These findings will facilitate the development of a subtype-oriented therapy strategy to enhance the treatment effect in the near future.

Characterization and discrimination of human colorectal cancer cells using terahertz spectroscopy.

Terahertz technology has been widely used in biomedical research. Herein, terahertz time-domain attenuated total reflection (THz TD-ATR) spectroscopy was employed to characterize and discriminate human cancer cell lines (DLD-1 and HT-29). Terahertz responses of the cell lines were measured and Savitzky-Golay algorithm was applied to smooth the spectra of refractive index, absorption coefficient and dielectric loss tangent in terahertz regime. Principal component analysis (PCA) was then adopted for feature extraction and cell characterization. Based on the processed data, cancer cell lines were discriminated by applying random forests (RF) method to analyze three characteristic parameters separately and the results from them were compared. Results indicate that absorption coefficient was the most sensitive parameter for cancer cell discrimination. Our study suggests great potential for human cancer cell recognition and provides experimental basis for liquid biopsy.

Ultra-mutated colorectal cancer patients with POLE driver mutations exhibit distinct clinical patterns.

POLE mutations, which lead to an ultramutated phenotype in colorectal cancer (CRC), have been reported as a promising marker in immunotherapy. We performed sequencing of CRC cases in Zhejiang University (ZJU) and extracted obtainable data from recently published results, including The Cancer Genome Atlas (TCGA), Japanese studies and clinical trials, to present clinical patterns of POLE driver-mutated CRC and reveal its heterogeneity. The rate of somatic POLE driver mutations has been reported as 2.60% (ZJU cohort), 1.50% (TCGA cohort), 1.00% (Japan cohort), and 1.00% (Lancet cohort). POLE driver mutations show a clearly increased mutation burden (mean TMB: 217.98 mut/Mb in ZJU; 203.13 mut/Mb in TCGA). Based on pooled data, more than 70.00% of patients with POLE driver mutations were diagnosed before they were 55 years old and at an early disease stage (Stage 0-II >70.00%), and more than 70.00% were male. Among Asian patients, 68.40% developed POLE driver mutations in the left-side colon, whereas 64.00% of non-Asian patients developed them in the right-side colon (p < 0.01). The top three amino acid changes due to POLE driver mutations are P286R, V411L, and S459F. Investigators and physicians should ascertain the heterogeneity and clinical patterns of POLE driver mutations to be better equipped to design clinical trials and analyze the data.