Survival Rate Of Cancer Patients Research Articles

Abstract 86: Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell outgrowth in adipose tissue

Abstract Despite the high 5-year survival rate for early-stage breast cancer patients, late recurrence of the disease remains a major challenge. Breast cancer can recur in approximately 20-25% of patients months to decades after an initial diagnosis, and there are few biomarkers that predict which patients will suffer from the recurrent disease. Unfortunately, this means clinicians and their patients must take a frustrating wait-and-see approach. Notably, disseminated tumor cells (DTCs) are frequently detected in early-stage breast cancer patients, and their presence predicts a higher chance of recurrence. However, why some patients with DTCs recur while others do not remains a mystery. Previous work has suggested that changes in the tumor microenvironment (TME) play an important role in the maintenance of tumor cell dormancy. When assessing the impact of doxorubicin (DOXO), a chemotherapeutic agent often used to treat breast cancer patients, on the TME, we noted that DOXO treatment led to the activation of dormant breast cancer cells in the visceral adipose tissue. Moreover, in accordance with the clinical observation that obese patients suffer a higher risk of cancer recurrence, we found that diet-induced obesity further exacerbated DOXO ability to reactivate dormant breast cancer cells in adipose tissue and this reactivation was associated with robust macrophage infiltration. These findings were interesting in light of our observation that tumor cells can metastasize to visceral fat depots in breast cancer patients. To understand why macrophages were recruited to the adipose tissue and how they led to tumor cell reactivation, we profiled the microenvironmental changes in visceral fat from Veh- and Doxo- treated mice using single-cell RNA-sequencing and found that the infiltrating macrophages exhibited unique pro-inflammatory and lipid-regulatory phenotypes. Our study provides novel insights into how TME impacts breast cancer dormancy and also highlights the importance of adipose tissue as a unique reservoir that potentiates cancer relapse. Citation Format: Qihao Ren, Jiayu Ye, Xiaoyu Yuan, Sheila Stewart. Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell outgrowth in adipose tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 86.

Abstract 1318: Potential mechanism of re-dissemination from lung metastases to tertiary sites in breast carcinoma: Tumor microenvironment of metastasis doorways and related pro-metastatic tumor phenotypes

Abstract Background: The five-year relative survival rate of female breast cancer patients with distant metastases is only 29%, compared to 99% for localized disease. Among all subtypes, triple negative breast cancer (TNBC) has the poorest outcome due to a high risk of early relapse with visceral organ metastases, and a lack of targeted therapies. Targeting metastatic burden could improve patient survival. Recent mouse and human genomic profiling studies show that metastasis is a complex and multidirectional process. Cancer cells can re-disseminate from one metastasis to tertiary sites. But the mechanism of re-dissemination is unknown. Breast cancer cells disseminate from primary tumors via Tumor MicroEnvironment of Metastasis (TMEM) doorways, composed of three cells: a tumor cell, a perivascular macrophage, and an endothelial cell. The direct and stable interaction of these cells cause transient and local vascular opening through which metastasis-competent tumor cells co-expressing invasive, stem, and dormant phenotypes that preferentially reside around TMEM doorways disseminate to distant sites. We hypothesize that TMEM doorways also form in lung metastases, enabling cancer cell re-dissemination to tertiary sites, which increases overall cancer burden and risk of death. Methods: We used MDA-MB-231 and MDA-MB-468 human TNBC cells to generate tumors in the 4th mammary fat pad of 6-8 weeks old NOD/SCID mice. Primary tumors were resected when 5-6 mm and fixed with 10% formalin. When lung metastases were visible via micro-Computed Tomography (microCT) fluorescent dextran was injected intravascularly, and lungs collected and fixed with 10% formalin. Triple immunohistochemistry was used to visualize TMEM doorways. To test TMEM doorway-mediated vascular opening, sequential slides were stained for extravascular dextran. Cells co-expressing stem (SOX9), invasive (MenaINV), and dormant (NR2F1) markers were visualized by immunofluorescent staining. The density of TMEM doorways, CSCs, invasive, and dormant cells was determined by automated image analysis. Results: We demonstrated the presence and activity of TMEM doorways in lung metastases. Within lung metastases, we also documented the presence of cancer cells with a pro-metastatic phenotype indicated by their co-expression of invasive (MenaINV), stemness (SOX9), and dormancy (NR2F1) markers. We will report how the expression of pro-metastatic markers relates to TMEM doorway niches. Conclusion: We documented functional TMEM doorways in lung metastases of TNBC, which could explain the occurrence of an early overall metastatic burden in patients with TNBC. Thus, targeting TMEM doorways after the removal of the primary tumor in patients with TNBC could block cancer cell re-dissemination, decrease metastases, and improve survival. Citation Format: Burcu Karadal-Ferrena, Camille L. Duran, Madeline Friedman-DeLuca, Nicole Barth, Prachiben Patel, John S. Condeelis, David Entenberg, Maja H. Oktay. Potential mechanism of re-dissemination from lung metastases to tertiary sites in breast carcinoma: Tumor microenvironment of metastasis doorways and related pro-metastatic tumor phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1318.

Abstract 3983: Defining the role of FANCA in breast cancer development and cell cycle progression

Abstract FANCA is one of the 22 known Fanconi anemia (FA) pathway genes and is indispensable for interstrand crosslink (ICL) repair. It is reported that FANCA is responsible for about 64% of FA cases and one important clinical characterization of FA patients is predisposition to cancer. However, analysis of TCGA database reveals that FANCA level is elevated in breast cancer patients, especially in ER- breast cancer, which is associated with the methylation status at the S-shore of CpG island ahead of FANCA gene. Moreover, the FANCA level is negatively correlated with the survival rate of breast cancer patients. To understand the implication of FANCA in breast cancer development, we have targeted FANCA by either CRISPR mediated knock-out (KO) or shRNA mediated knockdown (KD) in MDA-MB-231 breast cancer cells. Our data suggest that depletion of FANCA protein inhibits breast cancer growth both in vitro and in vivo. On the other hand, overexpressing FANCA in low-FANCA breast cancer cell line MDA-MB-468 promotes cancer cell proliferation. Cell cycle profiling reveals an inefficiency of MDA-MB-231 FANCA KO cells in G1 to S transition due to p21 and p27 upregulation in FANCA KO cells. In addition, the proliferation inefficiency in MDA-MB-231 FANCA KO cells is caused by Rb hypophosphorylation. Therefore, we conclude that FANCA contributes to the breast cancer development by promoting cell cycle progression through Rb/E2F signaling pathway. Our immunoprecipitation (IP) results indicate that in MDA-MB-231, FANCA is interacting with HES1, which is a transcription suppressor that binds to the promoter region of CDKN1A and CDKN1B to promote cell cycle progression, explaining how FANCA participates in cell cycle progression in breast cancer. Citation Format: Liang Luo, Wenjun Liu, Anna Palovcak, Fenghua Yuan, Fang Li, Daniel Calkins, Yan Li, Karoline Briegel, Daniel Bilbao, Evan Roberts, Christian Mason, Zhao-Jun Liu, Sylvia Daunert, Yanbin Zhang. Defining the role of FANCA in breast cancer development and cell cycle progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3983.

Abstract 4401: The precision chemotherapy to improve the epithelial ovarian cancer prognosis

Abstract Purpose: Recurrence is common in ovarian cancer patients, even in those patients who show complete response after first-line chemotherapy, 80% of the patients experience a recurrence. So gynecologic oncologists often have to consider several factors when choosing next chemotherapy regimen. Therefore, this study aimed to find serial chemotherapy regimen choice to anticipate patients’ better prognosis. Materials and Methods: We reviewed 656 patients diagnosed ovary cancer in one tertiary institutional hospital between 2006 and 2020. Patents’ clinic-pathologic characteristics, primary treatment, chemotherapy regimens, survival outcomes were collected. We divided patients into several groups according to their chemotherapy regimen by mechanism of action and compared them. 1st line chemotherapy(CTx) type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatin-paclitaxel, cisplatin-docetaxol2nd line CTx type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatin-paclitaxel, cisplatin-docetaxol2nd line CTx type 4: carboplatin-gemcitabine2nd maintenance CTx type 2: PARP inhibitor(PARPi)2nd line CTx Type 5: Platinum + topoisomerase inhibitor 2nd line CTx Type 6(cisplatin-vinorelbine)2nd line CTx Type 8(topoisomerase inhibitor only) 2nd line CTx Type12 (single taxol) The survival rate of ovary cancer patients decreased from stage 1 to stage 4.Among 1st line CTx type 1 and 2nd line CTx type(1 or 4) patients, those who used PARPi in 2nd line maintenance CTx(n=14) had a higher death rate than those who did not receive maintenance CTx or received that other than PARPi(hazard ratio 1.44). In the 1st line CTx 1~4 group, we divided patients according to 2nd line CTx type. We compare 2nd line CTx type 5 group(n=30) with type 6+8+12 group(n=26). The death rate was of type 5 group was higher than type 6+8+12 group. And Overall survival of 2nd line CTx type 5 group was 22 months, that of 2nd line CTx type 6+8+12 group was 26 months. Conclusion: When changing the chemotherapy regimen in the recurrence of ovarian cancer, the survival rate or overall survival may vary depending on the order in which the regimen is used. If we collect patients data more broadly, the predictive power will be better. Citation Format: Seongeun Pak, Youn Jin Choi. The precision chemotherapy to improve the epithelial ovarian cancer prognosis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4401.

Abstract 5759: Accelerated cardiac aging in adolescent and young adult cancer survivors previously treated with cardiotoxic therapy

Abstract Cancer in adolescents and young adults (AYA) is defined as cancer occurring between the ages of 15-39 years. Although cancer is the most common disease-related cause of death in this age group world-wide, the highly favorable overall 5-year survival rate for AYA cancer patients is creating a large and growing segment of the cancer survivorship population. Young cancer survivors have rates of comorbidities, frailty, and other phenotypes that are in line with that of individuals decades older, suggesting that cancer and/or treatment exposures accelerate the aging process in these survivors. Cardiotoxicity due to anthracycline and/or radiation exposure is a major contributor to poor cardiovascular health in AYA cancer survivors, yet the presence and the potential impact of accelerated cardiac aging remains unclear. We hypothesized that hearts in AYA cancer patients exposed to cardiotoxic treatment modalities have a functional phenotype that mirrors heart function in non-treatment exposed individuals who are decades older. In this cross-sectional study, 424 echocardiograms from 127 AYA Hodgkin lymphoma (N=98) and sarcoma (N=29) survivors who were treated with anthracyclines and/or radiation were reviewed for eight functional measures (left ventricular ejection fraction, A-wave, E-wave, E/A ratio, E’-wave, posterior wall thickness, mitral deceleration time, and left ventricular end-diastolic dimension). The median anthracycline dose received for the population was 291.0 mg/m2 (SD: 133.7) and 44.9% were exposed to radiation to the chest. At last follow-up, 8.3% were taking cardiac medications and 15.8% had been diagnosed with a cardiovascular disease during an average follow-up period of 5.6 years. Echocardiograms were obtained on average 1.3 years post-diagnosis (range: 0-14) and were grouped based at AYA survivor age at procedure (20-29 years, 30-39 years, and 40-49 years). Left ventricular ejection fraction (LVEF) and E’-wave were significantly lower than controls in all three age groups (P<0.001), with four other measures being significant in both of the two younger age groups (P<0.05). Strikingly, 90% of the population had more than one functional measure that was indicative of hearts at least two decades older than the patient at time of echocardiogram with AYA survivors having an average of 4.2 measures displaying evidence of accelerated cardiac aging. These results suggest that AYA cancer survivors exposed to cardiotoxic treatment modalities have a high burden of poor cardiac function and that accelerated cardiac aging may responsible. Citation Format: Michelle A. T. Hildebrandt, Cole J. Bernstein, Sairah Ahmed, J. Andrew Livingston, Efstratios Koutroumpakis, Michael E. Roth, Jose Banchs. Accelerated cardiac aging in adolescent and young adult cancer survivors previously treated with cardiotoxic therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5759.

Abstract 3801: Identification of circular RNAs associated with the ferroptosis of pancreatic cancer cells

Abstract The five-year survival rate for pancreatic cancer patients is significantly low which is predominately due to the lack of early-detection biomarkers, and poor response to currently available treatments that include drug resistance development. Recent studies suggest cancer cells can be highly sensitive to a newly defined type of cell death, ferroptosis, which is related to the development of resistance to standard chemotherapy drugs for pancreatic cancer such as gemcitabine and 5-Fluorouracil. However, the role of circular RNAs (circRNAs) in ferroptosis remains largely unexplored. Hence, this project aims to identify circRNAs in ferroptosis to uncover further components and mechanisms, and potentially provide specific effective targets for anticancer therapies. To achieve this, different ferroptosis inducers were tested, where the cystine-depletion method demonstrated higher efficiency based on cell viability and ferroptosis markers such as iron and lipid peroxidation levels. This method was used to induce ferroptosis for 24 hours in pancreatic cancer cells for subsequent circRNA sequencing, and to establish a ferroptosis-resistant cell line. From the sequencing data, 31 differentially expressed (DE) circRNAs were obtained, and eight were selected for further validation. Three circRNAs; circPPP2R2B, circNDUFAB1, and circNLN, showed consistent differential expression in ferroptosis non-resistant (downregulated) and resistant (upregulated) cells after cystine-depletion treatment. The knockdown of these circRNAs decreased the viability, invasion, migration, and colony formation ability of PDAC cells. Simultaneously, lipid peroxidation and intracellular iron levels, which are ferroptosis markers, were increased. Additionally, bioinformatic analysis of these circRNAs demonstrated their possible interaction with proteins and miRNAs with reported ferroptosis-related functions. In summary, these findings suggest that circPPP2R2B, circNDUFAB1, and circNLN may be critically involved in PDAC progression and the evasion of ferroptosis which supports the further investigation of their oncogenic and ferroptosis-related action mechanism to propose a potential target for anticancer therapies. Citation Format: Jessica Jazmin Pena Paladines, Shao Weng Wang, Chi Hin Wong, Yang Chao Chen. Identification of circular RNAs associated with the ferroptosis of pancreatic cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3801.

Abstract 1331: A novel approach to treating hormonal breast cancer using clinical database and 3D ex vivo model

Abstract Type 2 diabetes (T2D) female patients have a higher risk of being diagnosed and have worse survival for breast cancer compared to non-diabetic females. Although the relationship between these two female diseases has been reported, specific functional studies on which subtypes of breast cancer are affected and which genes are regulated by T2D are little known. Here, I found that Forkhead Box A1 (FOXA1) and Metformin, anti-diabetic medication for T2D, affect hormonal positive (HR+) breast cancer tumor cell growth and metastasis. 14 diabetes-related genes highly expressed in three HR+ breast cancer cell lines but not other breast cancer subtypes using a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4,032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Specifically, the high expression of FOXA1 correlated to a worse ER+/PR+ breast cancer patient survival rate. Consistent with this, the loss of FOXA1 inhibited the tumor proliferation and invasion of MCF-7 and T47D HR+ breast cancer cell lines using in vitro. Metformin (1,1-dimethylbiguanide hydrochloride) conspicuously inhibits the tumor cell growth in MCF-7 human hormonal breast cancer cells. Metformin or FOXA1 deletion enhanced Tamoxifen-mediated tumor growth inhibition in HR+ breast cancer cell lines through the ex vivo three-dimensional (3D) organoid model. Therefore, HR+ breast cancer is closely related to T2D, and metformin and FOXA1 inhibition might be an optimal new treatment for patients with HR+ breast cancer when combined with tamoxifen, a hormone therapy. Citation Format: Chaeun (Christine) Song, SeungBaek Lee. A novel approach to treating hormonal breast cancer using clinical database and 3D ex vivo model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1331.

Survival of Gastric Cancer Patients at a Tertiary Care Hospital in Eastern India: A Retrospective Data Analysis.

Background Gastric cancer is one of the most common cancers and a leading cause of death worldwide. Most cases of gastric cancer are diagnosed at an advanced stage when no definitive treatment is available leading to an overall declined survival rate. In this study, we aimed to investigate the survival rate of gastric cancer patients admitted to our tertiary care center and determined the relationship between sociodemographic and clinicopathological characteristics with mortality. Methodology Gastric cancer patients treated between January 2019 and December 2020 were included in this retrospective study. The clinicopathological and demographic data of 275 gastric cancer patients were analyzed. The Kaplan-Meier method was used to calculate the overall survival of gastric cancer patients. The Kaplan-Meier log-rank test was used to calculate the difference. Results The mean survival of gastric cancer patients was 20.10 months (95% confidence interval = 19.20-21.03). Deaths were higher among stage III (42.6%) and stage IV (36.1%) patients compared to stage I (1.6%) and stage II (19.7%) patients. Mortality was significantly higher (70.5%) in patients without surgery. Conclusions The mean survival in our study setting is lower and is associated with the pathological stage of the disease, surgical intervention, and patients presenting with other gastrointestinal symptoms. A lower survival ratecan be attributed to late diagnosis.

Targeted therapy for cisplatin-resistant lung cancer via aptamer-guided nano-zinc carriers containing USP14 siRNA.

Cisplatin (DDP) is a common therapeutic option for non-small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin-specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP-resistant lung cancer cells and couple them with nano-zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP-resistant lung cancer compared to DDP-sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin-resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer-targeted nano-zinc carriers were loaded with USP14 siRNA to target DDP-resistant lung cancer cells. Aptamer-targeted nano-zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer-guided nano-zinc carriers may be a potent carrier for the precise treatment of drug-resistant tumors.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer.

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model invitro. Invivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis.

Parafibromin is a protein encoded by the oncosuppressor CDC73 gene, whose mutation results in hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma. Down-regulation of parafibromin is linked to lung, gastric, colorectal, and ovarian cancer tumorigenesis. Parafibromin expression was detected by RT-PCR, bioinformatics analysis, Western blot, and immunohistochemistry; and compared with clinicopathological characteristics of breast cancer. CDC73-related genes and pathways were analyzed using bioinformatics analysis. Parafibromin expression was increased in breast cancer compared to normal tissues at both mRNA and protein levels (p<0.05). Among triple-negative breast cancers, it was higher in basal-like 1 than basal-like 2 patients (p<0.05) and mesenchymal than immunomodulatory patients (p<0.05). CDC73 mRNA expression was positively correlated with white race, non-infiltrating immune cells, favorable luminal subtypes of PAM50, and prognosis of breast cancer patients (p<0.05). The differential genes of CDC73 were classified into enzyme inhibitors, peptidase, and keratinization by KEGG (p<0.05). Similarly, it was classified into ribosomes, TGF-β, oxidation phosphorylation, inositol phosphate metabolism, arachidonic acid metabolism, linoleic acid metabolism, ERBB, and VEGF signaling pathways by GSEA (p<0.05). The positively-correlated genes of CDC73 were involved in cell mobility, response to interferon α, nuclear pore and basket, and histone methyltransferase. The negatively-correlated genes of CDC73 were involved in the mitochondrial respiratory chain, thermogenesis, and ribosomes. Parafibromin expression was higher in invasive ductal than lobular carcinoma (p<0.05) and mucinous adenocarcinoma than others (p<0.05). Parafibromin immunoreactivity as an independent factor was positively associated with an increased overall survival rate of breast cancer patients (p<0.05). These findings suggest that up-regulation of parafibromin in breast cancer patients is closely linked to a favorable prognosis. It is involved in tumorigenesis and subsequent progression by regulating metabolism, ribosomes, and cytokines.

Prediction and validation of survival rate of metachronous second primary lung cancer patients using machine learning classifiers

ABSTRACT Machine learning (ML) has been applied recently to develop prognostic classification models that can be used in individual cancer patients to forecast outcomes. Here, four different ML algorithms were built to predict survival rate of lung cancer patients using 1600 metadata records. Of note, the generated models were validated using test set and external validation data set consisting of 400 patient records each together with 10-fold cross-validation technique. The extratree classifier algorithm was employed to identify the influential descriptors for patients survival after incidence of metachronous second primary lung cancer. The models were assessed using five different performance metrices. The results from our study highlight that logistic regression model with all features and important features achieved an accuracy of 94% and 96%, respectively, for stratifying the survival status of lung cancer patients. On the other hand, logistic regression also outperformed external validation with an accuracy of 85%. Indeed, the results from our study will provide meaningful insights for the treatment and management of large community of lung cancer patients.

Cancer and Postradiotherapy Cardiotoxicity: How to Face Damage in Women's Hearts?

Cancer and cardiovascular disease are the two main causes of death worldwide in both men and women. In the past decades, survival rate in cancer patients has substantially improved due to new treatments and developments in radiation therapy (RT). In women, breast cancer (BC) is the leading cause of cancer death and thoracic RT is a main component of the treatment in many cases. Nevertheless, despite new techniques that limit the area receiving RT, cardiac damage is still an important concern in BC patients. In this review, the following aspects will be addressed: pathophysiology of postradiotherapy heart damage in women with BC; mechanisms, diagnosis and prevention/management of heart damage; and future areas of potential research for radiotherapy injury in women.

LncRNA SNHG4 Modulates EMT Signal and Antitumor Effects in Endometrial Cancer through Transcription Factor SP-1

Long non-coding RNAs (lncRNAs) are implicated in the initiation and progression of a variety of tumors, including endometrial cancer. However, the mechanisms of lncRNA in endometrial cancer formation and progression remain largely unknown. In this study, we confirmed that the lncRNA SNHG4 is upregulated in endometrial cancer and correlates with lower survival rates in endometrial cancer patients. Knock-down of SNHG4 significantly reduced cell proliferation, colonization, migration, and invasion in vitro, as well as modulating the cell cycle and reduced tumor growth of endometrial cancer in vivo. In addition, the effect of SNHG4 by the transcription factor SP-1 was confirmed in vitro. We found in this study that SNHG4/SP-1 plays an important role in endometrial cancer progression and may be used as a potential therapeutic and prognostic biomarker for endometrial cancer.

Study of MDM2 as Prognostic Biomarker in Brain-LGG Cancer and Bioactive Phytochemicals Inhibit the p53-MDM2 Pathway: A Computational Drug Development Approach.

An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein-protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein-ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target's active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.

PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis.

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-based search strategies were applied to databases including CENTRAL, MEDLINE, Embase, Web of Science and COSMIC. All studies assessing the impact of mutations in exon 9 and exon 20 of PIK3CA on survival rates of endometrial cancer patients were selected for inclusion. Statistical meta-analysis was performed with the 'meta' package in RStudio. Overall, 7 of 612 screened articles were included in the present study, comprising 1098 women with endometrial cancer. Meta-analysis revealed a tendency of impaired survival for patients with PIK3CA exon 9 and/or exon 20 mutations (RR 1.28; 95% CI 0.84, 1.94; p = 0.25). This tendency was consistent in subgroup analyses stratified by histologic type or -grade, with the most prominent effect in low-grade endometrial cancers (RR 2.04; 95% CI 0.90, 4.62; p = 0.09). In summary, these results suggest that PIK3CA mutations negatively influence survival outcomes of patients with endometrial cancer, including those with low-grade tumors.

LncRNA MIR17HG Suppresses Breast Cancer Proliferation and Migration as ceRNA to Target FAM135A by Sponging miR-454-3p

Breast cancer is one of the most common malignant tumors in women, and causes a large number of cancer-related deaths. The main cause of death of breast cancer patients is tumor recurrence and metastasis. Recent studies show that lncRNA (Long non-coding RNA) plays an important role in breast cancer. However, the overall biological activity and clinical consequences of the lncRNA MIR17HG in breast cancer remain unclear. Thus, we investigate how the MIR17HG/miR-454-3p network impacts breast cancer cell proliferation and migration. Given the TCGA and Oncomine databases, the researchers evaluated variations in MIR17HG expression for the survival rates of breast cancer patients. The influence of MIR17HG on cell proliferation, migration, cell cycle, and the mRNA expression level of miR-454-3p and FAM135A (family with sequence similarity 135 member A) is identified. Luciferase assay was used to detect the regulatory effect of miR-454-3p on the 3′UTR region of FAM135A, and rescue experiments demonstrated that MIR17HG can up-regulate FAM135A expression by competitively binding miR-454-3p. The effect of FAM135A on the cloning and invasion of MCF-7 cells was detected. MIR17HG expression is reduced in breast cancer tissues, and patients with greater levels of MIR17HG expression have a better prognosis. MIR17HG overexpression caused G2/M arrest in breast cancer cells according to a flow cytometry assay. FAM135A knockdown enhances breast cancer cell proliferation and clone creation, as well as two-dimensional and three-dimensional migratory capacities. Patients with high FAM135A expression in their breast cancer had a better prognosis. These novel findings indicate that MIR17HG may be a potential target for breast cancer. Our findings demonstrated that MIR17HG might suppress breast cancer cell proliferation and migration by sponge miR-454-3p through ceRNA(competing endogenous RNAs) mechanism, indicating that targeting MIR17HG may be a feasible therapeutic candidate for breast cancer.Graphical

Spline Model in The Case of Cervical Cancer Patient Resilience

Cervical cancer ranks highest in developing countries, and ranks 10th in developed countries as a cause of death for women. In Indonesia, cervical cancer ranks second out of the 10 most common cancers based on Anatomical Pathology data in 2010 with an incidence rate of 20 %. The number of new women with cervical cancer ranges from 90 - 100 cases per 100,000 population and every year there are 40 thousand cases of cervical cancer. Cervical cancer is a gynecological disease that has a high level of malignancy and is caused by the Human Papilloma Virus (HPV). One method that can be used in the analysis of human survival is survival analysis using the Cox proportional hazard model. This research will use the development of the Cox model using the Spline function as its basis. Based on the results obtained, the developed model can model the data well and give a low MSE. Based on the developed model, it is found that the variables that influence the survival rate of cervical cancer patients are age, stage, type of PRC transfusion treatment and comorbidities. HIGHLIGHTS Due to in silico study such as molecular docking, molecular dynamic simulation is an important computational method for drug design. It can be used to predict the binding orientation of small molecule drug candidates to their protein targets. In addition, docking is also can be applied to predict small molecule affinity and activity. Thus, molecular docking has an important role in drug discovery and rational design The ligand interaction with the receptor was more stable due to the decreased binding free energy value The lowest binding free energy and lowest RMSD value of this molecule, which may presumably cause compound 3 to has better binding affinity compare to other compounds GRAPHICAL ABSTRACT

Cinnamomi ramulus inhibits cancer cells growth by inducing G2/M arrest.

Introduction: Cinnamomi ramulus (CR) is one of the most widely used traditional Chinese medicine (TCM) with anti-cancer effects. Analyzing transcriptomic responses of different human cell lines to TCM treatment is a promising approach to understand the unbiased mechanism of TCM. Methods: This study treated ten cancer cell lines with different CR concentrations, followed by mRNA sequencing. Differential expression (DE) analysis and gene set enrichment analysis (GSEA) were utilized to analyze transcriptomic data. Finally, the in silico screening results were verified by in vitro experiments. Results: Both DE and GSEA analysis suggested the Cell cycle pathway was the most perturbated pathway by CR across these cell lines. By analyzing the clinical significance and prognosis of G2/M related genes (PLK1, CDK1, CCNB1, and CCNB2) in various cancer tissues, we found that they were up-regulated in most cancer types, and their down-regulation showed better overall survival rates in cancer patients. Finally, in vitro experiments validation on A549, Hep G2, and HeLa cells suggested that CR can inhibit cell growth by suppressing the PLK1/CDK1/ Cyclin B axis. Discussion: This is the first study to apply transcriptomic analysis to investigate the cancer cell growth inhibition of CR on various human cancer cell lines. The core effect of CR on ten cancer cell lines is to induce G2/M arrest by inhibiting the PLK1/CDK1/Cyclin B axis.