Specific Tumor Markers Research Articles

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor-specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Survival-related snoRNAs were selected to construct a specific snoRNA-based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein-protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co-expressed genes. Twelve prognosis-correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three-snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high-risk and low-risk cohorts using the risk model, and the high-risk group and activated B cell-like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co-expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co-expressed genes in DLBCL. Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review.

BACKGROUNDGallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored. AIMTo review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database. METHODSData of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)". RESULTSThe GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006–1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839–5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC.CONCLUSIONThe clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.

Assessment of Specific Tumoral Markers, Inflammatory Status, and Vitamin D Metabolism before and after the First Chemotherapy Cycle in Patients with Lung Cancer.

Simple SummaryIn patients with lung cancer, serum levels of neuron specific enolase were significantly decreased after the first chemotherapy cycle compared to pre-treatment values. In addition, the post-treatment values of neopterin were lower as well, but with marginal statistical significance. Conversely, circulating levels of chitotriosidase, squamous cell carcinoma antigen, vitamin D, and vitamin D receptor were not significantly modified in response to the first chemotherapy cycle.Background: We aimed to investigate the changes of inflammatory status reflected by serum levels of chitotriosidase (CHT) and neopterin, and how specific tumor markers such as neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCCA), as well as vitamin D metabolism assessed by vitamin D receptor (VDR) and 25-hydroxy vitamin D3 (25OHD3), were modified after the first cycle of chemotherapy in patients with lung cancer. Methods: We performed this first pilot study on twenty patients diagnosed with lung cancer by investigating the serum concentrations of CHT, neopterin, NSE, SCCA, VDR and 25OHD3 before and after the first cycle of chemotherapy. Results: The post-treatment values of NSE were significantly lower compared to the pre-treatment levels (14.37 vs. 17.10 ng/mL, p = 0.031). We noticed a similar trend in neopterin levels, but the difference was only marginally significant (1.44 vs. 1.17 ng/mL, p = 0.069). On the contrary, the variations of circulating SCCA, CHT, neopterin, VDR and 25OHD3, before and after treatment, did not reach statistical significance. Conclusion: Only circulating NSE was treatment responsive to the first chemotherapy cycle in patients with lung cancer, while inflammatory markers and vitamin D status were not significantly modified.

HIF‑1α and MBP1 are associated with the progression of breast cancer cells by repressing β‑catenin transcription.

Breast cancer (BC) is a common type of tumor. Numerous patients are diagnosed and treated in the early stages of the disease; however, the recurrence rate remains high. Therefore, identifying sensitive and specific tumor markers to prevent and treat BC is essential. c-Myc promoter binding protein 1 (MBP1) is a regulatory molecule located in the cell nucleus. It targets and regulates the expression of various cell proliferation-, apoptosis- and tumor-associated genes. MBP1 expression in BC tissues was detected using immunohistochemistry and further validated in BC and normal human cell lines using RT-qPCR and western blot analysis. Low MBP1 expression, in clinical samples of BC, was associated with a poor prognosis of BC (n=50). MBP1 overexpression effectively inhibited the growth and metastasis of xenograft tumors in vivo. Cell counting kit-8 assays confirmed that the proliferation of the BC cell lines was significantly increased following knockdown of MBP1 expression, while overexpression of MBP1 could significantly inhibit the proliferation of the BC cell lines. Mechanistically, a dual-luciferase assay was used to confirm that MBP1 was the key transcriptional regulator of β-catenin. In addition, MBP1 transcription and hypoxia-inducible factor (HIF-1α) induction were associated. By regulating the hypoxic microenvironmental state in the MDA231 and MCF7 cell lines, it was demonstrated that MBP1 served as a hypoxia-responsive factor and could be a new target for tumor therapy. Taken together, these results suggested that MBP1, as a potential tumor marker associated with prognosis of BC and may serve as a therapeutic target for BC. Moreover, MBP1 plays a critical role in inhibiting the growth and progression of BC cell lines.

Diagnostic value of CEUS LI-RADS and serum tumor markers for combined hepatocellular-cholangiocarcinoma

PurposeTo analyze the contrast-enhanced ultrasound (CEUS) manifestations of combined hepatocellular-cholangiocarcinoma (CHC) and to investigate the diagnostic value of the 2017 version of the CEUS Liver Imaging Reporting and Data System (LI-RADS) and serum tumor markers in CHC. MethodsA total of 66 pathologically confirmed CHC nodules were retrospectively analyzed. We summarized the CEUS manifestations of CHC and analyzed the relationship between serum tumor markers and the enhancement pattern of CHC. We also classified CHC according to CEUS LI-RADS criteria. The Kappa test was used to assess the interreader agreement of CEUS LI-RADS between radiologists. ResultAccording to the results, 52 of 62 (83.9%) patients had elevated alpha-fetoprotein (AFP), 19 of 61 (31.1%) had elevated carbohydrate antigen 199 (CA 199), and 13 of 61 (21.3%) had both elevated AFP and CA 199. Of the 66 CHC nodules, 64 (97.0%) were identified as malignant lesions by CEUS, 13 (19.7%) showed a hepatocellular carcinoma-like enhancement pattern, and 21 (31.8%) showed a cholangiocarcinoma-like enhancement pattern. For the CEUS LI-RADS categories, 39 of 53 (73.6%) CHC nodules were classified as LR-M, 12 (22.6%) were classified as LR-5, and 2 (3.8%) were classified as LR-4. The interreader agreement for the LI-RADS categories was 0.60. ConclusionsAlthough CHC lacks specific CEUS features, CEUS LI-RADS and serum tumor markers can be useful tools for reducing the misdiagnosis of CHC. In addition, due to the relative complexity of the CEUS features involved in CHC, it is necessary for beginning radiologists to learn more about CEUS features.

Indicators of correct targeting in stereotactic biopsy of intracranial lesions.

Background: Confirmation of whether a stereotactic biopsy was performed in the correct site is usually dependent on the frozen section or on novel tumor-specific markers that are not widely available. Immediate postoperative computed tomography (CT) or magnetic resonance (MR) is routinely performed in our service after biopsy. In this retrospective study, we have carefully analyzed these images in an attempt to determine the presence of markers that indicate appropriate targeting.Methods: Medical records and neuroimages of patients who underwent stereotactic biopsy of intracranial lesions were reviewed. The following variables were assessed: age, sex, anatomopathology, lesion site, complications, diagnostic accuracy, and the presence of image markers.Results: Twenty-nine patients were included in this case series. About 96.6% of the biopsies were accurate according to the permanent section. Of the 86.2% of patients with intralesional pneumocephalus on the postoperative images, 51.7% additionally presented petechial hemorrhage. In 13.8% of the cases, no image markers were identified.Conclusion: This is the first report of intralesional pneumocephalus and petechial hemorrhage as indicators of appropriate targeting in stereotactic biopsy. In the majority of the cases, an immediate postoperative head CT, which is widely available, can estimate how adequate the targeting is. To use intralesional pneumocephalus/ petechial hemorrhages as not only postoperative but also as intraoperative markers of appropriate targeting, it is advised that the surgical wound should be temporarily closed and dressed after the biopsy so that the patient can undergo a CT/MR scan and be checked for the presence of theses markers before removing the stereotactic frame.

Abstract 2832: Identifying tumor specific surface protein markers for glioblastoma immunotherapy by single-nuclei RNA-seq

Abstract Glioblastoma (GBM) is one of the deadliest adult brain tumors, in which the typical treatments of surgery, chemotherapy, and/or radiotherapy yield generally poor median survival. GBM is categorized into IDH-mutant subtype and IDH-wildtype subtype, which is subcategorized into proneural, classical, and mesenchymal subtypes, yet few personalized treatment options are available. The use of genetically modified chimeric antigen receptor T cells (CAR-T), such as CD19 CAR-T, has shown significant clinical efficacy in the treatment of hematological malignancies due to specific antitumor response; however, CAR-T response in GBM has been poor. Single nuclei RNA-seq (snRNA-seq) technology offers high-resolution profiling of different cell populations and their specific differential patterns. Accordingly, we developed a robust genomic analysis pipeline that can be applied to external datasets, tumor, and healthy samples. This was followed by unbiased systematic analysis of GBM tumor-specific cell surface markers using 18 single nuclei RNA sequencing (snRNA-seq) samples to identify GBM specific CAR-T targets allowing efficient tumor cells targeting and minimum off-target effects by CAR-T (1). We identified key potential targetable cell surface-specific markers and we also identified subtype-specific targets. Our findings provide insights into tumor-specific cell surface proteins that may be potential targets for engineered immunotherapy.

Abstract 296: Antigen-independent delivery of 4-1BB agonist to the tumor microenvironment improves immune response while reducing hepatotoxicity

Abstract Background: Clinical progress of α4-1BB has been impeded by hepatotoxicity. Current research is focused on improving targeted delivery of α4-1BB to the tumor using tumor-specific markers. However, targeted delivery of 4-1BB agonists to tumors faces challenges due to a lack of tumor biomarkers and effector T cells within tumors. To overcome these challenges, we developed antigen-independent targeting approach based on unnatural sugar-mediated metabolic glycoengineering and bio-orthogonal click chemistry to deliver α4-1BB to tumors. We utilized nanoparticles that can deliver a sugar analogue containing click-chemistry moiety to the tumor microenvironment. Method: The Ac4ManNAz was loaded in mPEG-PLGA nanoparticles (MazNP), and the loading efficiency was determined by HPLC. DBCO-functionalized α4-1BB (DBCO-α4-1BB) was synthesized via amine-NHS coupling reaction. The tumor inhibition efficiency was assessed on mice bearing different tumor models. Mice were either inoculated subcutaneously on the left flank (75,000 B16F10 cells) or injected on the left fourth mammary fat pad (100,000 4T1 cells). Mice were given MazNPs (IV) on day 5, 6, 10, and 11, and DBCO-α4-1BB (IV) and αPD-1 (IP) on day 8 and 13. T lymphocytes were analyzed by fluorescent IF staining. Serum liver enzyme was examined to evaluate hepatotoxicity of treatments. Liver pathology was assessed by H&amp;E and CD8+ IHC staining. Results: The αPD1 plus DBCO-α4-1BB with MazNPs showed a 36.4% cure rate, compared to 0% of αPD1 plus DBCO-α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz in B16F10 melanoma model. We then re-challenged the cured mice with 200,000 B16F10 cells and 50% of cured mice survived without any further treatment. In 4T1 breast cancer model, the survival data analyzed using the log-rank test showed that the median survival of αPD1 plus DBCO-α4-1BB with MazNP was increased by 71%, compared to the PBS, and 26% αPD1 plus α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz. We showed that the involvement of NK and CD8+ T cells in the antitumor efficacy of αPD1 plus DBCO-α4-1BB with MazNP. Notably, a massive CD8+ T cell infiltration in the liver was observed in both αPD1 plus α4-1BB (29.8 ± 18.2%) and αPD1 plus DBCO-α4-1BB with Ac4ManNAz (22.1 ± 10.9), significantly higher than PBS control (0.9 ± 0.6%), while the percentage of CD8+ T cells in the MazNP treatment (5.4 ± 5.8%) was five times lower. Hepatotoxicity was further confirmed by serum liver enzyme analysis that ALT and AST levels were substantially elevated by αPD1 plus α4-1BB or αPD1 plus DBCO-α4-1BB with free Ac4ManNAz, as compared to PBS control group, while the MazNP-treated mice had normal serum ALT and AST levels except for one. Conclusion: Our findings demonstrated that antigen-independent targeted delivery of α4-1BB can improve anti-tumor immune responses while reducing hepatotoxicity. Citation Format: Hyesun Hyun, Bo Sun, Stephanie A. Montgomery, Teresa Griffin, Juanzhu Yan, Albert Wielgus, Yue Wang, Tian Zhang, Jianjun Cheng, Andrew Z. Wang. Antigen-independent delivery of 4-1BB agonist to the tumor microenvironment improves immune response while reducing hepatotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 296.

Circulating DNA and Liquid Biopsies in the Management of Patients with Cancer.

Forty-five years ago, Cancer Research published the study by Leon and colleagues in which the authors described the observation of increased levels of cell-free DNA (cfDNA) in the serum of patients with cancer as compared with healthy individuals, with the highest serum levels in patients with metastatic cancer. Most interestingly was the correlation between serum DNA concentrations and therapy outcome: Increased serum DNA levels were associated with poor response to treatment, whereas decreases in DNA levels during treatment appeared to be a sign of better prognosis. Since the discovery of the prognostic value of blood DNA, much research has been focused on the characterization of cfDNA to understand its origins and increase the sensitivity and specificity of using cfDNA as a prognostic and predictive marker in the battle against cancer. Tumor-specific cfDNA markers that were discovered include genetic alterations, chromosomal aberrations, epigenetic modifications, and DNA fragmentation size. In recent years, due to the development of highly sensitive molecular technologies, cfDNA-based assays are now being introduced into the clinic as the so called "liquid biopsy." The advantages of a liquid biopsy over traditional biopsy and imaging have led to the implementation in the clinic for early cancer detection, improved cancer staging, early detection of relapse, real-time monitoring of therapeutic efficacy, and detection of therapeutic targets and resistance mechanisms. Despite Leon and colleagues' initial skepticism about the potential diagnostic value of serum DNA, cfDNA-based liquid biopsy has become one of the most important tools for personalized cancer treatment. See related article by Leon and colleagues, Cancer Res 1977;37:646-50.

Abstract 2800: Use of an optimized machine learning algorithm to develop DNA methylation markers for detecting colorectal cancer (CRC)

Abstract Introduction: Epigenetic changes including methylation occur early in tumorigenesis and are known to be highly pervasive across a tumor type. The DNA methylation pattern can vary between individuals with or without cancer and also in patients with cancer of different origins. In this study, we investigated the discovery of comprehensive markers and validation of the diagnostic and prognostic potential of colorectal cancer. Methods: Patients with various stage of colorectal cancer were eligible for the current study, mainly stage III. We generated genome-wide methylation data from 379 colorectal cancer (CRC) tissues and 330 available paired adjacent normal mucosa tissues from Korean patients by Illumina EPIC Human Methylation microarray targeting 860,000~ CpG sites. A machine learning algorithm was used to build an optimized prediction model and select the tumor specific markers based on through theses CpG sites. Then, the risk score was devised for prognosis using this marker set. Finally, in order to validate the rule of CpG sites, the genomic location and pathway enrichment analysis was performed by CHROMHMM and Metascape. Results: 379 colorectal cancer tissues and 330 paired adjacent normal mucosal tissues were included for analysis. Clinical stages of the included patients were, III in N (61.2%), II in N (19.5%), and IV in N (11.9%). A total of 305 methylation markers that showed statistically significant differences between normal and cancer tissues were selected. Our model could accurately identify CRC (areas under the curve for the training and validation cohorts: 0.968 and 0.984, respectively). Using our prediction model, the colorectal cancer patients were predicted as colorectal cancer accurately in the methylation data from TCGA (COREAD; colorectal cancer tissue DNA) and GEO dataset (plasma cfDNA from colorectal cancer patients). The risk score comprising the subset of 305 methylation markers was calculated, and poor prognosis was predicted in the high-risk score group (overall survival P &amp;lt;0.1, progression-free survival P &amp;lt; 0.01). Gene ontology (GO) enrichment analysis showed that the 305 CpG sites were enriched in transcription regulatory regions (160/305, 52.5%) and were associated with developmental process and carcinogenesis (GO: 0032502, P &amp;lt;0.001; C4721208, P &amp;lt;0.001). Conclusions: In summary, the performance of our prediction model with these 305 CpG sites was highly accurate for CRC diagnosis, and the optimized risk score could predict the prognosis of Korean CRC patients Citation Format: Jun-Kyu Kang, Su Yeon Kim, Yoojoo Lim, Hwang-Phill Kim, Tae-You Kim. Use of an optimized machine learning algorithm to develop DNA methylation markers for detecting colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2800.

Phase I/II first-in-human CAR T–targeting MUC1 transmembrane cleavage product (MUC1*) in patients with metastatic breast cancer.

TPS1130 Background: Metastatic breast cancer (MBC) remains incurable and novel immunotherapy for durable response remains an unmet need. Chimeric antigen receptor (CAR) T-cell therapy, an innovative form of immunotherapy wherein autologous T-cells are genetically modified to target tumor specific cell-surface markers, has been developed for treatment of solid tumors. huMNC2-CAR44 recognizes the growth factor receptor form of MUC1, which is the transmembrane cleavage product called MUC1*. MUC1* is a Class I growth factor receptor that is activated by ligand-induced dimerization of its truncated extra cellular domain, which activates the MAP kinase signaling pathway as well as survival pathways. Onco-embryonic growth factor NME7AB binds to an ectopic site on MUC1* that is only unmasked after MUC1 is cleaved and the tandem repeat domain is shed from the cell surface. The targeting head of the CAR, huMNC2, competes with NME7AB for binding to this ectopic site. huMNC2 does not bind to full-length MUC1, hence highly tumor-selective. 70% of solid tumor cancers express a huMNC2 reactive MUC1* and huMNC2-scFv bound robustly to 93% of the breast cancers with minimal staining of normal tissues. huMNC2-CAR44 T cells completely obliterated a variety of MUC1* positive solid tumors in NSG mice in vivo. IND enabling animal studies demonstrated that huMNC2-CAR44 T potently inhibited MUC1* positive tumors xenografted into female NSG mice, whether the tumor cells were MUC1 negative cells stably transduced with MUC1* or breast cancer cells such as T47D that naturally express MUC1*. In one study, huMNC2-CAR44 T treated mice survived tumor-free for over 12 weeks, whereas control group had to be sacrificed at 3 weeks due to disease progression. Methods: This is a first-in human, phase I/II trial evaluating the safety and efficacy of huMNC2-CAR44 T in patients with MBC. Key inclusion criteria include age ≥18 years, ECOGPS 0-1, available FFPE tumor sample, tumor IHC ≥30% MUC1* and preserved organ function. Dose escalation is standard 3+3 design with dosing levels ranging from 3.3x10^5 to 1.0x10^7 CAR+ cells/kg, and fludarabine/cyclophosphamide lymphodepletion pre-treatment. Phase I accepts patients with MBC that has progressed through at least 3 previous lines of therapy. The primary objective of Phase I is to determine safety and determine a recommended Phase II dose (RPIID), with the exploratory objectives of assessing CAR T cell expansion, persistence, tumor penetration and potential tumor escape. Six (6) patients have been enrolled and five (5) patients have been treated to date. Phase II will be comprised of 3 cohorts of 15 patients in each arm of luminal, HER2+ and triple negative breast cancers for a total of 45 patients in Phase II. Clinical trial information: NCT04020575.

Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.

e12563 Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.

TRIM29 is differentially expressed in colorectal cancers of different primary locations and affects survival by regulating tumor immunity based on retrospective study and bioinformatics analysis.

In colorectal cancer (CRC) patients, different primary tumor locations caused distinct prognosis and clinicopathological features. It is necessary to identify specific tumor markers according tumor site. Our previous work has identified differentially expressed genes between CRC and adjacent normal tissues, in which only TRIM29 was differently expressed between right colon cancer (RCC) and left colon cancer (LCC) patients. Rectal cancer (RECC) was not included in this latter study and the effects of TRIM29 on the survival with RCC and LCC patients were not investigated. This study further verified TRIM29 expression through Gene Expression Omnibus (GEO) database and our retrospective study. The role of TRIM29 on survival according tumor sites was also explored. Furthermore, the molecular mechanisms of TRIM29 were explored. The GEO dataset was used to confirm the differential expression of TRIM29 in proximal and distal cancers. Moreover, TRIM29 were assess using immunohistochemistry (IHC) in 227 cases to observe the correlation between TRIM29 and tumor site. The relationship between TRIM29 and the clinicopathologic features was investigated according tumor sites. Furthermore, the disease-free survival (DFS) and overall survival (OS) was analyzed using the Kaplan-Meier method to assess the prognostic value of TRIM29. Finally, bioinformatics analysis was used to explore the molecular mechanisms. The Tumor-Immune System Interactions and Drug Bank database (TISIDB) was used to analyze the correlations between TRIM29 expression and tumor immune functions. The correlation of TRIM29 with tumor infiltrating lymphocytes or mismatch-repair-proficient/mismatch-repair-deficient (pMMR/dMMR) status was also investigated. TRIM29 expression was significantly higher in patients with RCC (P<0.001). RCC patients with high TRIM29 tended to be older, male, in stage III-IV, with N+ staging, and intestinal obstruction (P<0.001, P<0.001, P<0.001, P<0.001, and P=0.010, respectively). High TRIM29 expression was associated with an increased risk of recurrence/metastasis and death, only in RCC patients (P=0.020 and P<0.001). Functional annotations and immune activity analysis showed that TRIM29 is related to tumor infiltrating lymphocytes and immune dysfunction. TRIM29 plays varying roles in patients with different tumor sites. TRIM29 is correlated with the clinicopathological features and prognosis in RCC patients. Indeed, TRIM29 may serve as a new biomarker for RCC patients.

Dual Rolling Circle Amplification-Assisted Single-Particle Fluorescence Profiling of Exosome Heterogeneity for Discriminating Lung Adenocarcinoma from Pulmonary Nodules

Dual Rolling Circle Amplification-Assisted Single-Particle Fluorescence Profiling of Exosome Heterogeneity for Discriminating Lung Adenocarcinoma from Pulmonary Nodules

BRCA-1 mediated activation of NF-κβ and its pro-inflammatory network drives tumorigenesis in benign breast disease patients

BackgroundBenign breast disease (BBD) is a broad spectrum of diseases that have been linked to an elevated risk of developing breast cancer to varying degrees. The specific relation between BBD and breast cancer is yet to be resolved. MethodsHence the present study was aimed to investigate the relationship between BRCA-1 mutation and its impact on specific tumor markers and inflammatory cytokines mRNA expression in peripheral blood samples of BBD (n = 25), breast cancer (CAB) subjects (n = 25) and compared with control subjects (n = 25) through RT-qPCR. ResultsResults showed that BRCA-1 gene polymorphism was observed in BBD patients and CAB patients. Further quantitative RT-PCR was performed to detect the relative mRNA expression of NF-κβ, P53, BCL-2, Caspase-3, COX-2, IL-1β, TNF-α, &IL-6 gene transcripts in all the samples. Results showed that the transcript levels of P53 &Caspase-3 were significantly down regulated in BRCA-1 positive CAB (p = 0.0001) followed by BRCA-1 positive BBD subjects (p = 0.0001) when compared to control subjects. Besides, mRNA expression of NF-κβ, BCL-2 COX-2, IL-1β, TNF-α, &IL-6 levels were significantly elevated in BRCA-1 positive breast cancer subjects (2.0-fold, p = 0.0001) followed by BRCA-1 positive BBD subjects (1.2-fold p = 0.001) compared to control subjects. ConclusionBRCA-1 germ line mutation plays a significant role in tumor progression and pathogenesis. Also, the link between BBD and BC are associated with impaired BRCA-1 mutation results in altered expression of tumor markers in peripheral blood leucocytes.

Prediction of the prognosis by the preoperative red blood cell distribution width in distal cholangiocarcinoma

Cholangiocarcinoma has a very poor prognosis, with no specific tumor markers or clear prognostic factors. The red blood cell distribution width (RDW) was recently suggested as an independent prognostic factor in cancer patients; however, no report has examined the association with distal cholangiocarcinoma. In this retrospective analysis of 38 patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma at Nagasaki Medical Center in Japan from January 2011 to December 2020, we explored whether or not the preoperative RDW was a prognostic factor in distal cholangiocarcinoma. Patients were divided into two groups (RDW-high: n = 20 vs. RDW-low: n = 18) according to the median preoperative RDW (13.6%). The T-Bil (1.75 vs. 0.9 mg/dl, p = 0.022) and CEA (2.95 vs. 1.95 ng/ml, p = 0.043) values were higher and the ALB (3.35 vs. 3.95 g/dl, p = 0.007) value was lower in the RDW-high group than in the RDW-low group. The RDW-high group had a poorer survival than the RDW-low group. The overall survival for the RDW-high group was 29.1 months, and that for the RDW-low group was 37.9 months (p = 0.042). However, there was no significant difference in the recurrence-free survival between the groups (p = 0.140). In conclusion, the preoperative RDW was suggested to be a possible prognostic factor in distal cholangiocarcinoma.

PET Imaging of Acidic Tumor Environment With 89Zr-labeled pHLIP Probes.

Acidosis of the tumor microenvironment is a hallmark of tumor progression and has emerged as an essential biomarker for cancer diagnosis, prognosis, and evaluation of treatment response. A tool for quantitatively visualizing the acidic tumor environment could significantly advance our understanding of the behavior of aggressive tumors, improving patient management and outcomes. 89Zr-labeled pH-low insertion peptides (pHLIP) are a class of radiopharmaceutical imaging probes for the in vivo analysis of acidic tumor microenvironments via positron emission tomography (PET). Their unique structure allows them to sense and target acidic cancer cells. In contrast to traditional molecular imaging agents, pHLIP’s mechanism of action is pH-dependent and does not rely on the presence of tumor-specific molecular markers. In this study, one promising acidity-imaging PET probe ([89Zr]Zr-DFO-Cys-Var3) was identified as a candidate for clinical translation.

MP46-05 CHARACTERIZING ONLINE TESTICULAR CANCER DISCUSSIONS WITH QUANTITATIVE THEMATIC ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP46-05 CHARACTERIZING ONLINE TESTICULAR CANCER DISCUSSIONS WITH QUANTITATIVE THEMATIC ANALYSIS Krishna Ravivarapu, Alexander Small, Micah Levy, Chih Peng Chin, Evan Garden, Osama Al-Alao, Joseph Sewell Araya, and Michael Palese Krishna RavivarapuKrishna Ravivarapu More articles by this author , Alexander SmallAlexander Small More articles by this author , Micah LevyMicah Levy More articles by this author , Chih Peng ChinChih Peng Chin More articles by this author , Evan GardenEvan Garden More articles by this author , Osama Al-AlaoOsama Al-Alao More articles by this author , Joseph Sewell ArayaJoseph Sewell Araya More articles by this author , and Michael PaleseMichael Palese More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002612.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients are increasingly turning to the internet to crowdsource community support and medical advice. This is especially true for younger patient populations like those affected by testicular cancer. Extracting information from online discussions can facilitate better counseling and care by giving providers insights into prevailing concerns, common misconceptions, and shared emotions. We aim to use quantitative natural language processing methodology to identify key themes of discussion in one of the internet’s largest testicular cancer forums. METHODS: We extracted three years of posts (08/2016 to 08/2019) and comments (01/2017 to 12/2019) from the 3,593 member Reddit community r/testicularcancer. The dataset was analyzed by a meaning extraction method followed by principal component analysis (MEM/PCA) to computationally distill major themes of discussion (Figure 1). Kaiser-Meyer-Olkin Measure of Sampling Adequacy (>0.60) and Bartlett’s test of sphericity (<0.001) indicate that the data is suitable for MEM/PCA. RESULTS: 17,423 posts and comments were analyzed with MEM/PCA to generate five major themes of discussion, ranked by prevalence: 1) chemotherapy and side effects 2) medical evaluation after self-identifying an anomaly, 3) cancer diagnosis and surgery, 4) blood test result discussion of specific tumor markers, and 5) medical decision-making. Users seeking medical advice, such as questions about self-identified testicular anomalies (“lump” 5.2%), are consistently referred to medical evaluation (“urologist” 6.3%, “oncologist” 5.3%). Posts can be very technical, referring to forms of testicular cancer (“seminoma” 4.1%, “embryonal [carcinoma]” 1.1%, “teratoma” 1.1%, “yolk [sac] carcinoma” 0.6%, and “choriocarcinoma” 0.3%) as well as specific tumor markers (“AFP” 1.5%, “HCG” 1.1%, “LDH” 0.6%). Regarding “chemotherapy” (17.5%), “hair [loss]” (2.4%) is a major concern. CONCLUSIONS: Social media forums allow patients to express unbiased and uninhibited thoughts and concerns. These anecdotes can collectively influence patient attitudes and approaches. Therefore, it is important for providers to be aware of the key topics of discussion on social media to connect better with their patients, improving shared decision-making, patient satisfaction, and care. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e774 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Krishna Ravivarapu More articles by this author Alexander Small More articles by this author Micah Levy More articles by this author Chih Peng Chin More articles by this author Evan Garden More articles by this author Osama Al-Alao More articles by this author Joseph Sewell Araya More articles by this author Michael Palese More articles by this author Expand All Advertisement PDF DownloadLoading ...

Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges

Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.

Calcifying fibrous tumor of the ileum resected by single-port laparoscopic surgery: a case report

BackgroundCalcifying fibrous tumors (CFTs) are rare benign tumors. Because CFTs sometimes relapse, radical resection with adequate margins is necessary. We report a case of ileal CFT resected using single-port laparoscopic surgery.Case presentationA 33-year-old man presented with chief complaints of abdominal pain and vomiting. Computed tomography demonstrated a 45-mm-sized pelvic mass with partial calcification in the ileum. The patient was diagnosed with an ileal tumor, and partial resection of the ileum was performed using the single-port laparoscopic technique. Pathologic findings revealed hypocellular spindle cells with dense hyalinized collagen, interspersed calcification, and infiltration of lymphoplasmacytic cells. Immunohistochemical analysis showed that the factor XIIIa was positive and other tumor-specific markers were negative. Based on these findings, the tumor was finally diagnosed as a CFT.ConclusionsAlthough CFT is benign, multifocal and recurrent CFTs have been reported. Therefore, careful intraperitoneal observation and curative resection are necessary. Single-port laparoscopic surgery is acceptable, both in terms of curability and minimal invasiveness.