Cancer Controls Research Articles

Whole-genome sequencing of East Asian lung cancers reveals new germline pathogenic variants.

In this issue of Cancer Cell, Wang etal. use whole-genome sequencing of lung cancer cases and controls with East Asian ancestry to comprehensively characterize both common and rare variants that predispose to lung cancer. Their findings suggest that rare promoter variants in BRCA2 are associated with increased lung cancer risk.

Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Seroconversion rate after COVID-19 vaccination in patients with solid cancer: A systematic review and meta-analysis

ABSTRACT Patients with solid cancer have an increased risk of severe coronavirus disease 2019 (COVID-19) and associated mortality than the general population. This meta-analysis aimed to investigate the currently available evidence about the efficacy of COVID-19 vaccines in patients with solid cancer. We included prospective studies comparing the immunogenicity and efficacy of COVID-19 vaccines between patients with solid cancer and healthy individuals. Relative risks of seroconversion after the first and second dose of a COVID-19 vaccine were separately pooled with the use of random effects meta-analysis. Thirty studies with 11,245 subjects met the inclusion criteria. After first vaccine dose, the pooled RR of seroconversion in patients with solid cancer vs healthy individuals was 0.54 (95% CI 0.38–0.78, I 2 = 94%). After a second dose, the pooled RR of seroconversion in patients with solid cancer vs healthy controls was 0.87 (0.86–0.88, I 2 = 87%). Our review suggests that, compared with healthy individuals, COVID-19 vaccines show favorable immunogenicity and efficacy in patients with solid cancer. A second dose is associated with significantly improved seroconversion, although it is slightly lower in patients with solid cancer compared with healthy individuals.

Expansion of Colorectal Cancer Biomarkers Based on Gut Bacteria and Viruses.

Simple SummaryThe current study identified microbial (including bacterial and viral) diagnostic models that could discriminate colorectal tumor patients from healthy controls, expanding the potential biomarkers for colorectal tumors. A combination of five colorectal cancer-associated gut bacteria was identified in this study for the discrimination of colorectal cancer patients from healthy controls, with verifiable performance in multiple cohorts. The gene pathways regulated by aberrant gut bacteria were also identified, providing possible directions for studying bacterial carcinogenesis mechanisms. Furthermore, this study revealed the potential interactions of gut bacteria with viruses and within bacteria in adenoma-carcinoma sequences, which may extend our understanding of dysbiosis in colorectal carcinogenesis.The alterations in gut bacteria are closely related to colorectal cancer. However, studies on adenoma are still scarce. Besides, the associations of gut viruses with colorectal tumor, and the interactions of bacteria with viruses in colorectal tumors are still under exploration. Therefore, a metagenomic sequencing of stool samples from patients with colorectal adenoma (CRA), colorectal cancer (CRC), and healthy controls was performed to identify changes in gut microbiome in patients with colorectal tumors. Five CRC-enriched bacteria (Peptostreptococcus stomatis, Clostridium symbiosum, Hungatella hathewayi, Parvimonas micra, and Gemella morbillorum) were identified as a diagnostic model to identify CRC patients, and the efficacy of the diagnostic model was verifiable in 1523 metagenomic samples from ten cohorts of eight different countries. We identified the positive association of Bacteroides fragilis with PD-L1 expression and PD-1 checkpoint pathway, providing a possible direction for studying bacterial carcinogenesis mechanisms. Furthermore, the increased interactions within the microbiome in patients may play roles in the development of CRC. In conclusion, this study identified novel microbiota combinations with discrimination for colorectal tumor, and revealed the potential interactions of gut bacteria with viruses in the adenoma-carcinoma sequence, which implies that the microbiome, but not only bacteria, should be paid more attention in further studies.

Does Obestatin Level Change in Endometrial Pathologies? A Case-Control Study in A Tertiary Care Hospital

Background: The rising incidence of endometrial cancer has been associated with increases in obesity and physical inactivity. We investigated the clinical significance of serum obestatin levels in women with endometrial cancer, endometrial hyperplasia, and age-matched healthy controls. 
 Material and Methods: The present study was a case-control study conducted at a single center between May 2014 and July 2015. The medical records of 90 patients with a final histopathologic diagnosis after therapeutic curettage for abnormal uterine bleeding were reviewed and categorized by diagnosis. The study population included women with adenocarcinoma of the endometrium (n= 33), hyperplasia of the endometrium (n= 27), and proliferative endometrium (n=30) according to histopathological diagnosis. The women with proliferative endometrium formed the control group.
 Results: Endometrial cancer was diagnosed in 33 (36.6%) of the patients who presented to our clinic for abnormal uterine bleeding. In the group with endometrial cancer, the mean age was 55.2 ± 8.6 years. There were no differences in obestatin levels between groups (p > 0.05). In the ROC curve analysis, the area under the curve value was 0.574, and obestatin did not prove to be a significant marker for cancer prediction in the population involved in the study.
 Conclusion: This study did not demonstrate a clear association between circulating levels of obestatin and endometrial pathologies.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with cervical cancer in an Algerian population

Angiotensin-converting enzyme (ACE) has been reported to be associated with the pathogenesis and progression of human cancers. Nevertheless, the details of that role remain inconclusive. We conducted this case-control study to determine the frequency of the ACE I/D polymorphism and its relationship to the risk of cervical cancer in the Algerian population. Genotype analysis of the ACE I/D polymorphism was performed using polymerase chain reaction (PCR) in DNA isolated from peripheral blood samples of 88 cervical cancer patients and 161 healthy controls subjects. Overall, the frequencies of ID, II, and DD genotypes showed a significant difference between cervical cancer patients and controls (p <0.0001). The I allele frequencies were more frequent in cervical cancer patients than in healthy subjects. Contrary to expectation, individuals’ carriers of the I allele (ID +II) had a significant increase in cervical cancer risk when using the genotype DD as the reference category (II+ID vs. DD: OR, 6; 95% CI, 2.71-13.29, p <0.0001). Our results indicate that ACE I/D polymorphism may contribute to the development of cervical oncogenesis and might be used as a common risk factor for cervical cancer susceptibility.

Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC

BackgroundA group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC).MethodsSoft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis.ResultsResults revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa.ConclusionKaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

Diagnostic value of carcinoembryonic antigen combined with cytokines in serum of patients with colorectal cancer.

In clinical practice, colorectal cancer (CRC) is difficult to distinguish from ulcerative colitis and colon polyps. Practical markers are useful for diagnosing and treating patients with CRC. Carcinoembryonic antigen (CEA) is a biomarker for diagnosing patients with CRC. However, the diagnostic sensitivity and specificity of CEA are not high. Interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and transforming growth factor beta (TGF-β) are assumed to be closely related to the occurrence and development of human cancer. Some have been used as diagnostic markers in CRC. It remains unclear whether cytokines in combination with CEA could be used as biomarkers for the diagnosis of CRC. Serum levels of IL-10, IL-17, TNF-α, IFN-γ, and TGF-β in patients with CRC, ulcerative colitis, colonic polyps, stomach cancer, and healthy controls were measured by enzyme-linked immunosorbent assay. The serum level of CEA was detected using electrochemiluminescence. The value of the cytokines combined with CEA as a biomarker panel for the diagnosis of CRC was assessed. CEA, IL-10, IL-17A, TNF-α, and TGF-β levels were significantly increased in CRC. CEA displayed a higher specificity than the other cytokines. IL-17A, TNF-α, and TGF-β displayed higher sensitivities than CEA, IL-10, and IFN-γ in the diagnosis of CRC. The combination of serum CEA, IL-17A, and TNF-α achieved higher diagnostic efficacy for CRC (area under the curve = 0.935). The combination of CEA, IL-17, and TNF-α has better diagnostic efficacy than CEA alone in CRC. A panel containing IL-17A, TNF-α, and CEA could be a promising molecular biomarker panel to diagnostically differentiate CRC from ulcerative colitis, colon polyps, and stomach cancer.

Allostatic load in patients with breast cancer

Breast cancer is the most common cancer in women worldwide. However, the allostatic load in breast cancer patients has not been sufficiently studied. Objective: to study the allostatic load in middle-aged and elderly patients with breast cancer. Material and methods. The study included 65 middle-aged and 60 elderly patients with histologically confirmed breast cancer and 45 people aged 60-74 years, who had no breast cancer. The allostatic load was studied in these three groups according to the level: systolic and diastolic blood pressure, total cholesterol, triglycerides, high and low density lipoproteins, glucose, albumins and waist circumference. Results. The allostatic load score was significantly higher in elderly breast cancer patients than in middle-aged breast cancer patients (4.3 ± 0.3 points versus 2.9 ± 0.2 points, p&lt;0.01). In addition, the allostatic load score in the middle-aged patients with breast cancer was significantly higher (2.7 ± 0.2 points) than in people of the same age, who had no breast cancer (1.6 ± 0.1 points). In elderly patients, the allostatic load score was also significantly higher in patients with breast cancer than in people without breast cancer (4.3 ± 0.3 points and 2.9 ± 0.2 points, respectively; p&lt;0.001). Significant differences in the allostatic load parameters, such as the levels of total cholesterol (5.8 ± 1.3 mmol/l versus 4.0 ± 0.8 mmol/l), and albumin (45.1 ± 7.4 % versus 61.4 ± 7.6 %) were found between breast cancer patients aged 60-74 years and people of an identical age, who had no breast cancer. statistically significant differences in allostatic load biomarkers, such as systolic blood pressure, diastolic blood pressure, blood levels of triglycerides and glucose, and waist circumference were found between elderly patients with breast cancer and age controls (without breast cancer). The content of triglycerides in the blood of patients aged 60-74 years with breast cancer was 1.8 times higher than that in patients of the same age with no breast cancer (p&lt;0.001). The blood glucose level was significantly higher in patients with breast cancer than in the age controls (5.8 ± 1.2 g/l versus 4.4 ± 1.1 g/l, p&lt;0.01). Conclusion. The allostatic load and its variables should be used as biomarkers of increased risk of breast cancer.

Role of apoptosis inhibitor of macrophages in patients with IgG4‑related disease/autoimmune pancreatitis and the clinical characteristics associated with this condition.

Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease (IgG4-RD) and is a unique chronic inflammatory disease characterized by fibrosis. IgG4-RD is caused by an autoimmune mechanism that mimics malignant tumors and inflammatory disorders. Apoptosis inhibitor of macrophages (AIM) can function as a biomarker of autoimmune or inflammatory diseases with tissue fibrosis, including in inflammatory bowel disease and chronic liver disease. Therefore, the aim of the present study was to clarify the role of serum AIM levels and the clinical characteristics of patients with IgG4-RD and AIP. For this purpose, serum AIM concentrations were assessed using ELISA and the association between AIM and the laboratory and clinical data from patients with IgG4-RD/AIP, patients with pancreatic cancer (PC) and healthy controls (HCs), was determined. The results demonstrated that the serum AIM concentrations were not associated with the laboratory data. However, the serum AIM levels were significantly elevated in patients with AIP compared with the HCs and patients with PC. Furthermore, the serum AIM levels significantly decreased following steroid therapy in patients with AIP who were in remission. Overall, the present study demonstrates that serum AIM levels may be a potentially useful biomarker for the differential diagnosis of AIP and for evaluating the therapeutic reactivity of affected patients.

Sleep disturbance among breast cancer survivors and controls from midlife to early older adulthood: Pink SWAN.

To compare sleep disturbance from 5years pre- to 5years post-diagnosis between breast cancer survivors (BCS) and women without cancer over the same period and to identify BCS subgroups exhibiting different sleep trajectories. Analyses included data from 152 BCS and 2163 controls from 20years of follow-up in the longitudinal Study of Women's Health Across the Nation (SWAN), a multi-racial/ethnic cohort study. SWAN participants were assessed approximately annually from 1995 to 2015 using a standardized protocol. Pink SWAN focused on women who reported no cancer at SWAN enrollment and developed incident breast cancer after enrollment or did not develop breast cancer. Nonparametric locally weighted scatterplot smoothing plots and linear mixed models were used to compare the prevalence of the most frequently reported sleep problem, frequently waking several times a night (a sleep maintenance problem) during the previous 2weeks, between BCS and controls in the 5years pre- to 5years post-diagnosis. We characterized heterogeneity among BCS on this sleep problem using group-based trajectories and examined pre-diagnosis variables as predictors of group membership. No differences were found between BCS and controls in prevalence of frequent nighttime awakenings either before or after diagnosis. Among BCS, three trajectory groups were identified. Thirty-seven percent of BCS had consistently low prevalence of waking several times per night, 30% had high prevalence, and 33% had increasing prevalence which started 2years pre-diagnosis. Prevalence of pre-diagnosis vasomotor symptoms, anxiety, depressive symptoms, and smoking differed among these groups. Among mid-aged women diagnosed with breast cancer, this diagnosis did not trigger/amplify a sleep maintenance problem. The majority of BCS had similar levels of this sleep problem from pre- to post-diagnosis. Although sleep maintenance problems were not amplified by a cancer diagnosis, a subset of BCS may have sleep issues that should be monitored and treated, as indicated.

Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk

BackgroundEndoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk. MethodsThe prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress. ResultsER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant. ConclusionThis case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer.

Novel computerized neurocognitive test battery is sensitive to cancer-related cognitive deficits in survivors.

There is increasing interest in developing new methods to improve sensitivity in detecting subtle cognitive deficits associated with cancer and its treatments. The current study aimed to evaluate the ability of a novel computerized battery of cognitive neuroscience-based tests to discriminate between cognitive performance in breast cancer survivors and controls. Breast cancer survivors (N = 174) and age-matched non-cancer controls (N = 183) completed the Enformia Cogsuite Battery of cognitive assessments, comprised of 7 computerized tests of multiple cognitive domains. Primary outcome measures included accuracy, reaction times (RT), and coefficients of variation (CV) for each task, as well as global scores of accuracy, RT, and CV aggregated across tests. Linear regressions adjusting for age, education, and remote vs. in-office administration showed that compared to non-cancer controls, survivors had significantly lower performance on measures of attention, executive function, working memory, verbal ability, visuospatial ability, and motor function. Survivors had significantly greater CV on measures of attention, working memory, and processing speed, and significantly slower RT on measures of verbal fluency. The Cogsuite battery demonstrates sensitivity to cancer-related cognitive dysfunction across multiple domains, and is capable of identifying specific cognitive processes that may be affected in survivors. The sensitivity of these tasks to subtle cognitive deficits has advantages for initial diagnosis of cancer-related cognitive dysfunction, as well as detecting changes in survivors' cognitive function over time. The remote delivery of the battery may help overcome barriers associated with in-office administration and increase access to neurocognitive evaluation.

Impact on breast cancer susceptibility and clinicopathological traits of common genetic polymorphisms in TP53, MDM2 and ATM genes in Sardinian women.

Common variants of genes involved in DNA damage correction [tumor protein p53 (TP53), murine double 2 homolog oncoprotein (MDM2) and ataxia-telengiectasia mutated (ATM)] may serve a role in cancer predisposition. The purpose of the present study was to investigate the association of five variants in these genes with breast cancer risk and clinicopathological traits in a cohort of 261 women from northern Sardinia. Polymorphic variants in TP53 (rs17878362, rs1042522 and rs1625895), MDM2 (rs2279744) and ATM (rs1799757) were determined by PCR and TaqMan single nucleotide polymorphism assay in patients with breast cancer (n=136) and healthy controls (n=125). Association with clinicopathological (e.g., age at diagnosis, lymph node involvement, clinical stage) and lifestyle factors (e.g., smoking status, alcohol intake, contraceptive use) was also evaluated. TP53 rs17878362 and rs1625895 polymorphisms were associated with decreased risk of BC diagnosis in patients older than 50 years (codominant and recessive models) and post-menopause (recessive model). Furthermore, there was a significant association between lymph node status (positive vs. negative) and ATM rs1799757-delT in dominant and additive models and between MDM2 rs2279744-allele and use of oral contraceptives. This analysis suggested that TP53 rs17878362 and rs1625895 may affect age of onset of breast cancer and ATM rs1799757 and MDM2 rs2279744 may be associated with lymph node status and prolonged use of oral contraceptives, respectively.

DiaPASEF Proteomics and Feature Selection for the Description of Sputum Proteome Profiles in a Cohort of Different Subtypes of Lung Cancer Patients and Controls.

The high mortality, the presence of an initial asymptomatic stage and the fact that diagnosis in early stages reduces mortality justify the implementation of screening programs in the populations at risk of lung cancer. It is imperative to develop less aggressive methods that can complement existing diagnosis technologies. In this study, we aimed to identify lung cancer protein biomarkers and pathways affected in sputum samples, using the recently developed diaPASEF mass spectrometry (MS) acquisition mode. The sputum proteome of lung cancer cases and controls was analyzed through nano-HPLC–MS using the diaPASEF mode. For functional analysis, the results from differential expression analysis were further analyzed in the STRING platform, and feature selection was performed using sparse partial least squares discriminant analysis (sPLS-DA). Our results showed an activation of inflammation, with an alteration of pathways and processes related to acute-phase, complement, and immune responses. The resulting sPLS-DA model separated between case and control groups with high levels of sensitivity and specificity. In conclusion, we showed how new-generation proteomics can be used to detect potential biomarkers in sputum samples, and ultimately to discriminate patients from controls and even to help to differentiate between different cancer subtypes.

Female breast cancer incidence predisposing risk factors identification using nationwide big data: a matched nested case-control study in Taiwan

BackgroundBreast cancer is an umbrella term referring to a group of biologically and molecularly heterogeneous diseases originating from the breast. Globally, incidences of breast cancer has been increasing dramatically over the past decades. Analyses of multiple clinical “big data” can aid us in clarifying the means of preventing the disease. In addition, predisposing risk factors will be the most important issues if we can confirm their relevance. This study aims to provide an overview of the predisposing factors that contribute to a higher possibility of developing breast cancer and emphasize the signs that we ought to pay more attention to.MethodsThis is a matched nested case-control study. The cohort focused on identifying the eligible risk factors in breast cancer development by data screening (2000-2013) from the Taiwan National Health Insurance Research Database (NHIRD) under approved protocol. A total of 486,069 females were enrolled from a nationwide sampled database, and 3281 females was elligible as breast cancer cohort, 478,574 females who had never diagnosed with breast cancer from 2000 to 2013 were eligible as non-breast cancer controls, and matched to breast cancer cases according to age using a 1:6 ratio.ResultsWe analyzed 3281 breast cancer cases and 19,686 non-breast cancer controls after an age-matched procedure. The significant predisposing factors associated with breast cancer development including obesity, hyperlipidemia, thyroid cancer and liver cancer. As for patients under the age of 55, gastric cancer does seem to have an impact on the development of breast cancer; compared with their counterparts over the age of 55, endometrial cancer appears to exhibit an evocative effect.ConclusionsIn this nationwide matched nested case-control study, we identified obesity, hyperlipidemia, previous cancers of the thyroid, stomach and liver as risk factors associated with breast cancer. However, the retrospective nature and limited case numbers of certain cancers still difficult to provide robust evidence. Further prospective studies are necessitated to corroborate this finding in order to nip the disease in the bud.Trial registrationThe studies involving human participants were reviewed and approved by the China Medical University Hospital [CMUH104-REC2-115(AR-4)].

Cancer-specific Mortality in T1a Renal Cell Carcinoma Treated with Local Tumor Destruction Versus Partial Nephrectomy

BackgroundLarge-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. ObjectiveTo compare CSM after LTD versus PN. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004–2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. Outcome measurements and statistical analysesAfter 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). Results and limitationsRelative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1–4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. ConclusionsIn T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1–4 cm than in those with tumor size ≤3 cm. Patient summaryIn patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1–4 cm, but was also present in those with tumor size ≤3 cm.

Native Thiol, Total Thiol, and Dynamic Disulfide Profile in Patients with Gastrointestinal System Cancer

This study aims to evaluate the use of serum native thiol (NT), total thiol (TT), and dynamic disulfide (DD) levels as biomarkers in patients with gastrointestinal system (GIS) cancer with different cancer types by comparing with healthy controls. A total of 108 subjects consisting of68 patients with GIS cancer and 40 healthy individuals as a control group were included in the study. Serum NT, TT, and DD levels were measured by an automated method developed by Erel. There was a statistically significant difference between NT levels of GIS cancer and the control group (P = 0.001). However, there were no significant differences between male and female patients in terms of serum NT levels (P = 0.08). Similarly, no significant difference was observed when comparing serum NT levels among GIS cancer types (P = 0.886). The serum TT levels were statistically significant difference (P = 0.013) in GIS cancer, 141.82 ± 48.24 μmol/l (12.7-243.9) compare to the control group, 166.03 ± 56.23 μmol/l (12.7-326.8). When the serum TT and DD levels of the patients were compared according to gender, no significant difference was found (P = 0.243 and P = 0.362, respectively). In addition, the TT levels were not significantly difference among GIS malignancies (P = 0.765). When the patient and control groups were compared in terms of DD levels, no statistically significant difference was found (P = 0.378). In conclusion, it was determined that some parameters differ statistically between patients with GIS cancer and healthy controls. Therefore, there is a significant relationship between the thiol/disulfide balance with GIS cancer. This result suggests that oxidative stress may play a role in the development of the GIS cancer, consistent with the findings in this study, but not in terms of DD levels.

Diagnostic value of tumor associated autoantibody panel in early detection of lung cancer in Chinese population: Protocol for a prospective, observational, and multicenter clinical trial

Lung cancer is the leading cause of cancer deaths. Although targeted therapies and programmed cell death protein 1 (PD-1) blockade have offered great advances, five-year survival rates remained low. Diagnosis of lung cancer at an earlier stage is the most efficient approach to improve survival. Tumor associated autoantibodies (TAAb) have been proven a promising innovative biomarker of lung cancer. We aimed to comprehensively evaluate the sensitivity, specificity, and accuracy of TAAbs in lung cancer detection, especially in early-stage patients, through a multicenter prospective observational clinical trial, and to screen out the novel combination of TAAbs with the best detection value for Chinese population. We aimed to enroll 1,400 participants from three clinical centers and divide into two cohorts. One cohort is participants with newly pathologically confirmed lung cancer as the case cohort, and the other is participants with benign nodules, matched healthy controls and other benign lung diseases as the control cohort. Cases and controls were randomly distributed into training or validation set. The level of 14 autoantibody candidates in their plasma were detected. A Monte-Carlo Simulated Annealing method was implemented to develop a composite panel of autoantibodies to distinguish between matched lung cancer cases and controls in the training set. The newly developed autoantibody panel was tested in the validation set for sensitivity, specificity and accuracy. This is the first and largest clinical trial designed to develop a novel autoantibody panel for lung cancer detection specifically for Chinese people. We performed a multicenter, prospective, observational study to find a novel panel of autoantibody markers that can help the diagnosis of lung cancer and the characterization of pulmonary nodules in Chinese population. The results may help to provide evidence-based recommendations to clinicians for lung cancer early detection and pulmonary nodule management. This study is registered in the ClinicalTrials.gov (NCT04216511).

Arsenic Speciation and Metallomics Profiling of Human Toenails as a Biomarker to Assess Prostate Cancer Cases: Atlantic PATH Cohort Study.

Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.