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IntroductionThis study aimed to evaluate the feasibility of using general Raman spectroscopy as a method to screen for breast cancer. The objective was to develop a machine learning model that utilizes Raman spectroscopy to detect serum samples from breast cancer patients, benign cases, and healthy subjects, with puncture biopsy as the gold standard for comparison. The goal was to explore the value of Raman spectroscopy in the differential diagnosis of breast cancer, benign lesions, and healthy individuals.MethodsIn this study, blood serum samples were collected from a total of 333 participants. Among them, there were 129 cases of tumors (pathologically diagnosed as breast cancer and labeled as cancer), 91 cases of benign lesions (pathologically diagnosed as benign and labeled as benign), and 113 cases of healthy controls (labeled as normal). Raman spectra of the serum samples from each group were collected. To classify the normal, benign, and cancer sample groups, principal component analysis (PCA) combined with support vector machine (SVM) was used. The SVM model was evaluated using a cross-validation method. ResultsThe results of the study revealed significant differences in the mean Raman spectra of the serum samples between the normal and tumor/benign groups. Although the mean Raman spectra showed slight variations between the cancer and benign groups, the SVM model achieved a remarkable prediction accuracy of up to 98% for classifying cancer, benign, and normal groups. DiscussionIn conclusion, this exploratory study has demonstrated the tremendous potential of general Raman spectroscopy as a clinical adjunctive diagnostic and rapid screening tool for breast cancer.

BackgroundFruquintinib, a vascular endothelial growth factor receptor inhibitor, is a new anticancer drug independently developed in China to treat refractory metastatic colorectal cancer (mCRC). In Japan, regorafenib combined with nivolumab has been demonstrated to be promising in patients with refractory mCRC. Here, in a real-world study, we were aimed to evaluate the efficacy of fruquintinib with various programmed death-1 (PD-1) inhibitors after standard treatment in Chinese non-microsatellite instability-high (MSI-H)/mismatch repair proficient mCRC patients.MethodsA total of 45 patients with refractory mCRC were involved in the study. They received fruquintinib (3 or 5 mg, orally administered once a day for 3 weeks followed by 1 week off in 4-week cycles) and a PD-1 inhibitor(200 mg pembrolizumab, 3 mg/kg nivolumab, 200 mg sintilimab or camrelizumab, intravenously administered on D1 once every 3 weeks). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and objective response rate (ORR) were reviewed and evaluated.ResultsAmong the 45 patients, the median age was 54 years (29-85). The ORR was 11.1% (5/45), DCR 62.2% (28/45), median PFS equal 3.8 months, and median OS was 14.9 months. The response duration was 3.4 months. PFS between left and right primary tumors and PFS with or without lung metastases were both not significantly different (p > 0.05), which was inconsistent with the result of REGONIVO study. The multivariate analysis indicated no association of OS benefit in the specified subgroups. No adverse-effect-related deaths were reported.ConclusionsFruquintinib, in combination with anti-PD-1, was observed to have clinical activity in a small population of patients with heavily pretreated mCRC in our center. Further studies are needed to verify this outcome in a large population.

BackgroundIn our previous phase II study, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment for advanced pancreatic adenocarcinoma (APAC). This study aimed to evaluate the effectiveness and safety of S-1 maintenance after NPS in APAC and to explore factors predicting survival benefits when using S-1 maintenance.MethodsBetween 2014 and 2018 a total of 182 patients with APAC, who were primarily treated with NPS, were included. For patients without progression or with treatment discontinuation due to any reasons within 4 months during NPS treatment, S-1 monotherapy was administrable as maintenance therapy at the physicians’ discretion based on the patients’ preference and performance status. Efficacy and safety of S-1 maintenance were investigated.ResultsIn 123 patients without progression within 4 months during NPS treatment, 74 received S-1 maintenance and had median progression-free survival of 9.6 months and median overall survival of 16.7 months. Multivariable analysis showed that in patients receiving S-1 maintenance after first-line NPS therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, non-metastatic disease, and complete or partial response as best response to NPS chemotherapy were independently associated with better survival. The most common all-grade hematological and non-hematological adverse events were neutropenia (82.4%) and peripheral neurotoxicity (66.2%), respectively, and the most common ≥Grade 3 hematological and non-hematological adverse events were neutropenia (40.5%) and peripheral neurotoxicity (6.8%), respectively in patients who received S-1 maintenance.ConclusionsOur real-world study showed that S-1 maintenance after tumor response or stable disease induced by first-line NPS treatment was effective and well-tolerated for some patients with APAC, which offers a promising alternative treatment strategy with encouraging survival for APAC.

BackgroundBiomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.MethodsWe retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.ResultsWe included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).ConclusionsOur study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

BackgroundThere are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC.MethodsWe retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan–Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed.ResultsThis study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%).ConclusionsAnti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.

ObjectiveThis study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC).Methods3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites.ResultsA total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07).ConclusionMolecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

BackgroundIncreasing evidence has suggested that inflammation is related to tumorigenesis and tumor progression. However, the roles of immune-related genes in the occurrence, development, and prognosis of glioblastoma multiforme (GBM) remain to be studied.MethodsThe GBM-related RNA sequencing (RNA-seq), survival, and clinical data were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Immune-related genes were obtained from the Molecular Signatures Database (MSigDB). Differently expressed immune-related genes (DE-IRGs) between GBM and normal samples were identified. Prognostic genes associated with GBM were selected by Kaplan–Meier survival analysis, Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and multivariate Cox analysis. An immune-related gene signature was developed and validated in TCGA and CGGA databases separately. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore biological functions of the signature. The correlation between immune cell infiltration and the signature was analyzed by single-sample gene set enrichment analysis (ssGSEA), and the diagnostic value was investigated. The gene set enrichment analysis (GSEA) was performed to explore the potential function of the signature genes in GBM, and the protein–protein interaction (PPI) network was constructed.ResultsThree DE-IRGs [Pentraxin 3 (PTX3), TNFSF9, and bone morphogenetic protein 2 (BMP2)] were used to construct an immune-related gene signature. Receiver operating characteristic (ROC) curves and Cox analyses confirmed that the 3-gene-based prognostic signature was a good independent prognostic factor for GBM patients. We found that the signature was mainly involved in immune-related biological processes and pathways, and multiple immune cells were disordered between the high- and low-risk groups. GSEA suggested that PTX3 and TNFSF9 were mainly correlated with interleukin (IL)-17 signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway, and the PPI network indicated that they could interact directly or indirectly with inflammatory pathway proteins. Quantitative real-time PCR (qRT-PCR) indicated that the three genes were significantly different between target tissues.ConclusionThe signature with three immune-related genes might be an independent prognostic factor for GBM patients and could be associated with the immune cell infiltration of GBM patients.

Mounting evidence has revealed that many nontumor cells in the tumor microenvironment, such as fibroblasts, endothelial cells, mesenchymal stem cells, and leukocytes, are strongly involved in tumor progression. In hematological malignancies, tumor-associated macrophages (TAMs) are considered to be an important component that promotes tumor growth and can be polarized into different phenotypes with protumor or antitumor roles. This Review emphasizes research related to the role and mechanisms of TAMs in hematological malignancies. TAMs lead to poor prognosis by influencing tumor progression at the molecular level, including nurturing cancer stem cells and laying the foundation for metastasis. Although detailed molecular mechanisms have not been clarified, TAMs may be a new therapeutic target in hematological disease treatment.

ObjectiveExplore the influence of family history of upper gastrointestinal (UGI) cancer on UGI cancer death, based on the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.MethodsFamily history of UGI cancer was defined as at least one first-degree relative (parent, child, or sibling) had a history of esophageal or gastric cancer. Cancer death was carried out by ICD-10 code. Family history information was collected at baseline and cancer deaths were assessed at each annual follow-up. The COX proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). We compared the positive family history group with the negative to determine the risk of family history on UGI cancer death. The effect of category of relatives, number of relatives with UGI cancer, and diagnosis age of relatives on the UGI death risk were further analyzed. Interaction and stratification analyses were done to see the subgroup effects. Sensitivity analyses were also conducted by exclusion of individuals who were followed up less than three years. We considered controlling of covariates including: gender, age (continuity), community, education level, number of siblings (continuity), BMI (continuity), smoking, alcohol use, fresh fruit intake, fresh vegetable intake, hot beverage intake, edible oil intake, meat intake, and moldy staple food intake. All food intake variables were converted into categorical variables.ResultsFrom1985 to2015, we followed up total 3,318 individuals with 898 UGI cancer deaths (537 from ESCC, 77 from GNCC, and 284 from GCC). In a single factor analysis, family history of UGI cancer increased the risk of death of esophageal squamous cell carcinoma (ESCC) by 27% (HR=1.270, 95%CI1.072-1.504). No associations were observed in gastric cardia carcinoma (GCC) and gastric non-cardia carcinoma (GNCC). After adjusting for multi-factor, a family history of UGI cancer risk of death increased by 31.9% from ESCC (HR=1.319,95%CI:1.110-1.567). Subgroup analysis of different types of relatives with UGI cancers, UGI cancers in the mother (HR=1.457,95%CI:1.200-1.768), brother (HR=1.522,95%CI:1.117-2.073), and sister (HR=1.999,95%CI:1.419-2.817) were independent risk factors for ESCC death, while the father was not. In addition, 2 relatives with UGI cancer (HR=1.495, 95%, CI:1.110-2.013) and ≥3 relatives with UGI cancer (HR=2.836, 95%CI:1.842-4.367) significantly increased the risk of ESCC death, and the trend test was statistically significant (P

World Health Organization (WHO) data show that of the top 20 factors that threaten human life and health, cancer is at the forefront, and the therapeutic approaches for cancer consist of surgery, radiotherapy, chemotherapy and immunotherapy. For most highly metastatic and recurrent cancer, radiation therapy is an essential modality to mitigate tumor burden and improve patient survival. Despite the great accomplishments that have been made in clinical therapy, an inevitable challenge in effective treatment is radioresistance, the mechanisms of which have not yet been completely elucidated. In addition, radiosensitization methods based on molecular mechanisms and targets, and clinical applications are still inadequate. Evidence indicates that circular RNAs (circRNAs) are important components in altering tumor progression, and in influencing resistance and susceptibility to radiotherapy. This review summarizes the reasons for tumor radiotherapy resistance induced by circRNAs, and clarifies the molecular mechanisms and targets of action. Moreover, we determine the potential value of circRNAs as clinical indicators in radiotherapy, providing a theoretical basis for circRNAs-based strategies for cancer radiotherapy.

ObjectiveThe objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models.ResultsThere were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HRESCC = 1.45, 95%CI: 1.35–1.56; HRGCC = 1.27, 95%CI: 1.15–1.40; Mortality: HRESCC = 1.40, 95%CI: 1.30–1.52; HRGCC = 1.27, 95%CI: 1.14–1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HRESCC = 1.65, 95%CI: 1.40–1.95; HRGCC = 1.42, 95%CI: 1.12–1.81) and deaths (HRESCC = 1.65, 95%CI: 1.38–1.97; HRGCC = 1.42, 95%CI: 1.09–1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17–1.47; Mortality: HR = 1.33, 95%CI: 1.17–1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results.ConclusionOur data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.

BackgroundPostoperative cerebral edema is common in patients with meningioma. It is of great clinical significance to predict the postoperative cerebral edema exacerbation (CEE) for the development of individual treatment programs in patients with meningioma.ObjectiveTo evaluate the value of three-dimensional radiomics Features from Multi-Parameter MRI in predicting the postoperative CEE in patients with meningioma.MethodsA total of 136 meningioma patients with complete clinical and radiological data were collected for this retrospective study, and they were randomly divided into primary and validation cohorts. Three-dimensional radiomics features were extracted from multisequence MR images, and then screened through Wilcoxon rank sum test, elastic net and recursive feature elimination algorithms. A radiomics signature was established based support vector machine method. By combining clinical with the radiomics signature, a clin-radiomics combined model was constructed for individual CEE prediction.ResultsThree significance radiomics features were selected to construct a radiomics signature, with areas under the curves (AUCs) of 0.86 and 0.800 in the primary and validation cohorts, respectively. Two clinical characteristics (peritumoral edema and tumor size) and radiomics signature were determined to establish the clin-radiomics combined model, with an AUC of 0.91 in the primary cohort and 0.83 in the validation cohort. The clin-radiomics combined model showed good discrimination, calibration, and clinically useful for postoperative CEE prediction.ConclusionsBy integrating clinical characteristics with radiomics signature, the clin-radiomics combined model could assist in postoperative CEE prediction before surgery, and provide a basis for surgical treatment decisions in patients with meningioma.

Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.