The relationship between urologic cancer outcomes and national Human Development Index: trend in recent years.

OBJECTIVES: To describe the influence of the socioeconomic development on worldwide age-standardized incidence and mortality rates, as well as mortality-to-incidence ratio (MIR) and 5-year net survival of urologic cancer patients in recent years. METHODS: The Human Development Index (HDI) values were obtained from the United Nations Development Programme, data on age-standardized incidence/mortality rates of prostate, bladder and kidney cancer were retrieved from the GLOBOCAN database, 5-year net survival was provided by the CONCORD-3 program. We then evaluated the association between incidence/MIR/survival and HDI, with a focus on geographic variability as well as temporal patterns during the last 6 years. RESULTS: Urologic cancer incidence rates were positively correlated with HDIs, and MIRs were negatively correlated with HDIs. Prostate cancer survival also correlated positively with HDIs, solidly confirming the interrelation among cancer indicators and socioeconomic factors. Most countries experienced incidence decline over the most recent 6 years, and a substantial reduction in MIR was observed. Survival rates of prostate cancer have simultaneously improved. CONCLUSION: Development has a prominent influence on urologic cancer outcomes. HDI values are significantly correlated with cancer incidence, MIR and survival rates. HDI values have risen along with increased incidence and improved outcomes of urologic caner in recent years.

Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.

Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6Chi monocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6Clo monocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C-C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.

Urinary Molecular Pathology for Patients with Newly Diagnosed Urothelial Bladder Cancer.

PURPOSE: Next-generation sequencing (NGS)-based profiling of both urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) shows promise for noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, the analytical performance of these assays remains undefined in the real-world setting. Here, we sought to evaluate the concordance between tumor DNA (tDNA) profiling and utDNA or ctDNA assays using a UBC patient cohort from the intended-use population. MATERIALS AND METHODS: Fifty-nine cases with pathologically confirmed disease and matching tissue/urine pairs were prospectively enrolled. Baseline peripheral blood mononuclear cell and plasma specimens were collected during clinic visits. The PredicineCARETM NGS assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tDNA, utDNA and ctDNA. RESULTS: Diverse quantitative metrics including cancer cell fraction, variant allele frequency and tumor mutation burden were invariably concordant between tDNA and utDNA, but not ctDNA. The mutational landscapes captured by tDNA or utDNA were highly similar, whereas a considerable proportion of ctDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed somatic events as reference, utDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value of 67.2%, a negative predictive value of 99.8% and a diagnostic accuracy of 99.1%. Higher preoperative utDNA or tDNA abundance correlated with worse relapse-free survival. Actionable variants including FGFR3 alteration and ERBB2 amplification were identified in utDNA. CONCLUSIONS: Urine-based molecular pathology provides a valid and complete genetic profile of bladder cancer, and represents a faithful surrogate for genotyping and monitoring newly diagnosed UBC.

Vortex and symmetric radiation character of nonlinear Thomson scattering in Laguerre-Gaussian circularly polarized laser pulses.

The radiation character of nonlinear Thomson scattering is investigated in the interaction of Lagueree-Gaussian circularly polarized laser pulses with a single electron in the angular plane. With theoretical analysis and numerical calculation, it is shown that the angular radiation distributions have annular structures with great fourfold or plane symmetry in pulses characterized by comparatively lower laser intensity (a0 < 6), prolonged pulse duration (τ > 50fs)or wide beam waist (b0 > 5µm). In other circumstances, a vortex radiation pattern is found for the first time on the basis of the electron dynamics. Further, by increasing the initial phase of laser pulse, the overall angular radiation has an interesting counter-clockwise rotating trend with a cycle of Δξ0 = 2π. These results would help the understanding of nonlinear Thomson scattering and push forward the research of twisted X/γ-ray generation in optical laboratory.

Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy.

BACKGROUND/AIMS: Newly identified IL-10-producing regulatory B cells (Bregs) have been shown to play an important role in the suppression of immune responses. Chronic immune activation participates in the pathogenesis of dilated cardiomyopathy (DCM) but whether Bregs are involved in its development remains unclear. We aimed to investigate the circulating frequency and function of Bregs in DCM. METHODS: In total, 35 DCM patients (20 men and 15 women) and 44 healthy controls (23 men and 21 women) were included in the experiment, and the frequency of Bregs was detected using flow cytometry. RESULTS: According to our results, the frequency of circulating IL-10-producing Bregs was significantly lower in DCM patients compared with healthy controls. Furthermore, the CD24hiCD27+ B cell subset in which IL-10-producing Bregs were mainly enriched from DCM patients showed impaired IL-10 expression and a decreased ability to suppress the TNF-α production of CD4+CD25- Tconv cells and to maintain Tregs differentiation. Correlation analysis showed that the frequency of IL-10-producing Bregs and the suppressive function of CD24hiCD27+ B cells were positively correlated with left ventricular ejection fraction and negatively correlated with NT-proBNP in DCM patients. CONCLUSIONS: In conclusion, the reduced frequency and impaired functions suggest a potential role of Bregs in the development of DCM.

Expression of vitamin D receptor in clear cell papillary renal cell carcinoma.

Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized subtype of renal cell carcinoma. In this study, we investigated the clinicopathological and immunohistochemical features in a group of 26 cases of ccpRCC, with a special emphasis on the expression of vitamin D receptor (VDR). The mean age of patients was 53.3 years (range 36-74 years), and the mean tumor size was 2.5 cm (range 0.5 to 6.5 cm). During follow-up (range 12-121 months, median 50 months), no recurrence or metastasis was observed. Histopathologically, all cases of ccpRCC exhibited a tubular and papillary architecture, covered by tumor cells with clear cytoplasm. Immunohistochemistry showed intermediate (5/26, 19%) to diffuse (21/26, 81%) and moderate (2/26, 8%) to strong (24/26, 92%) membranous staining for VDR in each case. All cases (26/26, 100%) were diffuse and strong cytoplasmic and fibrillar staining for cytokeratin 7 (CK7), but negative forα-methylacyl-CoA-racemase (AMACR). Each case showed diffuse (26/26, 100%) and moderate (4/26, 15%) to strong (22/26, 85%) membranous staining for carbonic anhydrase IX (CA IX). In addition, the majority of cases showed negative for cluster of differentiation 10 (CD10) (20/26, 77%) and renal cell carcinoma maker (RCC-Ma) (24/26, 92%). This unique staining pattern is helpful for distinguishing ccpRCC from its mimics. Furthermore, VDR positive expression suggests that ccpRCC originates from the precursor epithelium of distal nephron.

Polymorphisms in the uncoupling protein 3 gene and their associations with feed efficiency in chickens.

OBJECTIVE: The uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily and has crucial effects on growth and feed efficiency in many species. Therefore, the objective of the present study was to examine the association of polymorphisms in the UCP3 gene with feed efficiency in meat-type chickens. METHODS: Six single nucleotide polymorphisms (SNPs) of the UCP3 gene were chosen to be genotyped using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in meat-type chicken populations with 724 birds in total. Body weight at 49 (BW49) and 70 days of age (BW70) and feed intake (FI) in the interval were collected, then body weight gain (BWG) and feed conversion ratio (FCR) were calculated individually. RESULTS: One SNP with a low minor allele frequency (<1%) was removed by quality control and data filtering. The results showed that rs13997809 of UCP3 was significantly associated with BWG and FCR (p<0.05), and that rs13997811 had significant effects on BW70 and BWG (p<0.05). Rs13997812 of UCP3 was strongly associated with BW70, FI, and FCR (p<0.05). Furthermore, individuals with AA genotype of rs13997809 had significantly higher BWG and lower FCR (p<0.05) than those with AT genotype. The GG individuals showed strongly higher BW70 and BWG than AA birds in rs13997811 (p<0.05). Birds with the TT genotype of rs13997812 had significantly greater BW70 and lower FCR compared with the CT birds (p<0.05). In addition, the TAC haplotype based on rs13997809, rs13997811, and rs13997812 showed significant effects on BW70, FI, and FCR (p<0.05). CONCLUSION: Our results therefore demonstrate important roles for UCP3 polymorphisms in growth and feed efficiency that might be used in meat-type chicken breeding programs.

Microarray bioinformatics in cancer- a review.

Bioinformatics is one of the newest fields of biological research, and should be viewed broadly as the use of mathematical, statistical, and computational methods for the processing and analysis of biological data. Over the last decade, the rapid growth of information and technology in both "genomics" and "omics" eras has been overwhelming for the laboratory scientists to process experimental results. Traditional gene-by-gene approaches in research are insufficient to meet the growth and demand of biological research in understanding the true biology. The massive amounts of data generated by new technologies as genomic sequencing and microarray chips make the management of data and the integration of multiple platforms of high importance; this is then followed by data analysis and interpretation to achieve biological understanding and therapeutic progress. Global views of analyzing the magnitude of information are necessary and traditional approaches to lab work have steadily been changing towards a bioinformatics era. Research is moving from being restricted to a laboratory environment to working with computers in a "virtual lab" environment. The present review article shall put light on this emerging field and its applicability towards cancer research.

Folic acid-conjugated TiO2-doped mesoporous carbonaceous nanocomposites loaded with Mitoxantrone HCl for chemo-photodynamic therapy.

Recently, porous carbons have showed great potential in many areas. In this study, TiO2-doped mesoporous carbonaceous (TiO2@C) nanoparticles were obtained by a simple one-pot hydrothermal treatment, folic acid (FA) was conjugated to TiO2@C through an amide bond, then Mitoxantrone HCl (MTX) was adsorbed onto TiO2@C-FA and a drug delivery system, TiO2@C-FA/MTX was obtained. TiO2@C-FA/MTX showed a much faster MTX release at pH 4.5 than at pH 6.0 and pH 7.4. Furthermore, compared with free MTX, this drug delivery system showed a dose-dependent cytotoxicity by varying the irradiance, and afforded higher antitumor efficacy in cultured PC3 cells in vitro. The ability of TiO2@C-FA/MTX to combine chemotherapy with photodynamic activity enhanced the cancer cell killing effect in vitro, demonstrating that TiO2@C-FA/MTX has a great potential for cancer therapy in the future.

Comprehensive analysis of MAPK genes in the prognosis, immune characteristics, and drug treatment of renal clear cell carcinoma using bioinformatic analysis and Mendelian randomization.

Mitogen-activated protein kinase (MAPK) signalling is vitally important in tumour development and progression. This study is the first to comprehensively analyse the role of MAPK-family genes in the progression, prognosis, immune-cell infiltration, methylation, and potential therapeutic value drug candidates in ccRCC. We identified a novel prognostic panel of six MAPK-signature genes (MAP3K12, MAP3K1, MAP3K5, MAPK1, MAPK8, MAPK9), and introduced a robust MAPK-signature risk model for predicting ccRCC prognosis. Model construction, evaluation, and external validation using datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database demonstrated its stability, as well as high sensitivity and specificity. Enrichment analysis suggested the participation of immune-mediated mechanism in MAPK dysregulation in ccRCC. Immune-infiltration analysis confirmed the relationship and revealed that the MAPK-signature risk model might stratify immunotherapy response in ccRCC, which was verified in drug sensitivity analysis and validated in external ccRCC immunotherapy dataset (GSE67501). Potential therapeutic drug predictions for key MAPKs using DSigDB, Network Analyst, CTD, and DGIdb were subsequently verified by molecular docking with AutoDock Vina and PyMol. Mendelian randomization further demonstrated the possibilities of the MAPK-signature genes as targets for therapeutic drugs in ccRCC. Methylation analysis using UALCAN and MethSurv revealed the participation of epigenetic modifications in dysregulation and survival difference of MAPK pathway in ccRCC. Among the key MAPKs, MAP3K12 exhibited the highest significance, indicating its independent prognostic value as single gene in ccRCC. Knockout and overexpression validation experiments in vitro and in vivo found that MAP3K12 acted as a promoter of tumour progression in RCC, suggesting a pivotal role for MAP3K12 in the proliferation, migration, and invasion of RCC cells. Our findings proposed the potential of MAPK-signature genes as biomarkers for prognosis and therapy response, as well as targets for therapeutic drugs in ccRCC.

Can major public health emergencies increase the participation of commercial insurance? Evidence from China.

Background: Public health emergencies have a lasting impact on a country's economic and social development. However, commercial insurance can disperse these negative consequences and reduce risk losses. Method: Based on the Chinese Household Tracking Survey and Peking University Digital Inclusive Finance Index, this study employed a difference-in-differences model to test the impact of the COVID-19 outbreak on commercial insurance participation and the impact mechanism. Results: The analysis showed that the outbreak of COVID-19 improved residents' risk perception, risk preference and digital finance and promoted their participation in commercial insurance, commercial endowment insurance, and commercial medical insurance. Conclusion: Major public health emergencies can increase commercial insurance participation, but the promotional effect of commercial insurance on rural and low-income individuals is relatively limited. To tap into potential customers, financial institutions should focus on vulnerable societal groups. This study supplements the relevant literature on the impact of major public health emergencies on commercial insurance participation.

Unveiling the State Transition Mechanisms of Ras Proteins through Enhanced Sampling and QM/MM Simulations.

In cells, wild-type RasGTP complexes exist in two distinct states: active State 2 and inactive State 1. These complexes regulate their functions by transitioning between the two states. However, the mechanisms underlying this state transition have not been clearly elucidated. To address this, we conducted a detailed simulation study to characterize the energetics of the stable states involved in the state transitions of the HRasGTP complex, specifically from State 2 to State 1. This was achieved by employing multiscale quantum mechanics/molecular mechanics and enhanced sampling molecular dynamics methods. Based on the simulation results, we constructed the two-dimensional free energy landscapes that provide crucial information about the conformational changes of the HRasGTP complex from State 2 to State 1. Furthermore, we also explored the conformational changes from the intermediate state to the product state during guanosine triphosphate hydrolysis. This study on the conformational changes involved in the HRas state transitions serves as a valuable reference for understanding the corresponding events of both KRas and NRas as well.

Cell membrane patches transfer CAR molecules from a cellular depot to conventional T cells for constructing innovative fused-CAR-T cells without necessitating genetic modification.

Chimeric antigen receptor (CAR) serves as the foundational element of CAR-T cells. Exogenous CAR molecules can exert functional effects on allogeneic T cells, leading to their activation and subsequent functional alterations. Here we show a new method based on this biological principle: the transfer of CAR molecules from exogenous cells to the membrane of receptor T cells. This process facilitates receptor T cell to recognize target antigens and induces their activation. These patches imbued normal T cells with enhanced tumor targeting capabilities and activated their inherent killing functions. This method's efficacy introduces an approach for constructing non-genetically manipulated CAR-T cells and holds potential for application to other immune cells.

Progress in the treatment of malignant ascites.

Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Versatile chondroitin sulfate-based nanoplatform for chemo-photodynamic therapy against triple-negative breast cancer.

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer.

Engineering M1 macrophages with targeting aptamers for enhanced adoptive immunotherapy by modifying the cell surface.

Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells. However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy. To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy.

Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling.

Clinical lymphatic metastasis indicates an extremely poor prognosis. Patients with papillary renal cell carcinoma (pRCC) have a high probability of progressing to lymphatic metastasis. However, the molecular mechanism of pRCC-associated lymphatic metastasis has not been elucidated. In this study, we found a downregulated long non-coding RNA (lncRNA) MIR503HG in pRCC primary tumor tissues due to hypermethylation at the CpG islands within its transcriptional start site. Decreased MIR503HG expression could stimulate tube formation and migration of human lymphatic endothelial cell (HLEC) and play a central role to promote lymphatic metastasis in vivo by enhancing tumor lymphangiogenesis. MIR503HG, located in the nucleus, bound with histone variant H2A.Z and affected the recruitment of histone variant H2A.Z to chromatin. Subsequently, increasing the H3K27 trimethylation caused by MIR503HG-overexpression epigenetically downregulated the NOTCH1 expression, which ultimately resulted in decreasing VEGFC secretion and lymphangiogenesis. Additionally, downregulated MIR503HG facilitated the HNRNPC expression, which ultimately promoted the maturation of NOTCH1 mRNA. Notably, upregulating MIR503HG expression might decrease pRCC resistance to the mTOR inhibitor. Together, these findings highlighted a VEGFC-independent mechanism of MIR503HG-mediated lymphatic metastasis. MIR503HG, identified as a novel pRCC-suppressor, would serve as the potentially biomarker for lymphatic metastasis.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Liaocheng in Summer].

Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.

Surface-Enhanced Raman Spectroscopy of Pretreated Plasma Samples Predicts Disease Recurrence in Muscle-Invasive Bladder Cancer Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy.

Objective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms. Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm-1, 1328 cm-1 and 1455 cm-1. The SERS also detected significantly lower levels of tryptophan shown as lower significantly intensities at the 1558 cm-1, which is proved to be an independent predictor of BCa recurrence. The addition of SERS peaks of 1558 cm-1 to classic clinicopathological predictors including pathological tumor stage, lymph node metastasis and pathological downstaging can significantly enhance the power of the predictive model from 0.66 to 0.76 in the area under curve (AUC) of receiver operating characteristic (ROC) curves. Meanwhile, the PCA-LDA diagnostic model based on SERS spectra reveals a high accuracy of 85.2% in prediction of disease recurrence and the AUC of 0.92 in the ROC curve. When validated in the leave-one-out cross-validation method, the accuracy of the model remained 84.1%. Conclusion: We show that SERS analysis of plasma before NAC treatment can accurately classify patients with different risks of disease recurrence after surgery and improve the power of clinicopathological predictive models, thus refining clinical decision-making.