Cancer Clinical Stage Research Articles

DPM1 expression as a potential prognostic tumor marker in hepatocellular carcinoma.

BackgroundAltered glycosylation of proteins contributes to tumor progression. Dolichol phosphate mannose synthase (DPMS), an essential mannosyltransferase, plays a central role in post-translational modification of proteins, including N-linked glycoproteins, O-mannosylation, C-mannosylation and glycosylphosphatidylinositol anchors synthesis. Little is known about the function of DPMS in liver cancer.MethodsThe study explored the roles of DPMS in the prognosis of hepatocellular carcinoma using UALCAN, Human Protein Atlas, GEPIA, cBioPortal and Metascape databases. The mRNA expressions of DPM1/2/3 also were detected by quantitative real-time PCR experiments in vitro.ResultsThe transcriptional and proteinic expressions of DPM1/2/3 were both over-expressed in patients with hepatocellular carcinoma. Over-expressions of DPMS were discovered to be dramatically associated with clinical cancer stages and pathological tumor grades in hepatocellular carcinoma patients. In addition, higher mRNA expressions of DPM1/2/3 were found to be significantly related to shorter overall survival in liver cancer patients. Futhermore, high genetic alteration rate of DPMS (41%) was also observed in patients with liver cancer, and genetic alteration in DPMS was associated with shorter overall survival in hepatocellular carcinoma patients. We also performed quantitative real-time PCR experiments in human normal hepatocytes and hepatoma cells to verify the expressions of DPM1/2/3 and results showed that the expression of DPM1 was significantly increased in hepatoma cells SMMC-7721 and HepG2.ConclusionsTaken together, these results suggested that DPM1 could be a potential prognostic biomarker for survivals of hepatocellular carcinoma patients.

A Comprehensive Analysis of Treatment Management and Survival Outcomes in Nasopharyngeal Carcinoma.

To comprehensively investigate nasopharyngeal carcinoma (NPC) treatment, overall survival (OS), and the influence of clinical/sociodemographic factors on outcome. Retrospective database study. National Cancer Database. The 2004-2015 National Cancer Database was queried for all patients with NPC receiving definitive treatment. Log-rank tests and Cox proportional hazards models were used for statistical analyses. A total of 8260 patients with NPC were included (71.4% male; 42.5% with keratinizing histology; mean ± SD age, 52.1 ± 15.1 years), with a 5-year OS of 63.4%. Multivariate predictors of mortality included age ≥65 years (hazard ratio [HR], 1.81; P < .001), Charlson/Deyo score ≥1 (HR, 1.27; P = .001), American Joint Committee on Cancer clinical stage III to IV (HR, 1.85; P < .001), and government insurance or no insurance (HR, 1.53; P < .001). Predictors of survival included female sex (HR, 0.82; P = .002), Asian/Pacific Islander race (HR, 0.74; P < .001), nonkeratinizing/undifferentiated histology (HR, 0.79; P = .004), and receiving treatment at academic centers (HR, 0.87; P = .02). Chemoradiotherapy (CRT) demonstrated improved OS as compared with radiotherapy (RT) only for stage II (P = .006) and stage III (P = .005) and with RT or chemotherapy only in stage IVA NPC (P < .001). When compared with CRT alone, surgery plus CRT provided OS benefits in keratinizing (P = .013) or stage IVA (P = .030) NPC. When compared with RT, CRT provided OS benefits in keratinizing (P = .005) but not nonkeratinizing (P = .240) or undifferentiated (P = .390) NPC. Substandard radiation dosing of <60 Gy and <30 fractions were associated with inferior OS (both P < .001). NPC survival is dependent on a variety of clinical/sociodemographic factors. Stage-specific treatments with optimal OS include CRT or RT for stages I to II and CRT for stage III to IV. The large representation of nonendemic histology is valuable, as these cases are not well characterized.

Lateral lymph node dissection reduces local recurrence of locally advanced lower rectal cancer in the absence of preoperative neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

BackgroundThe impact of lateral lymph node dissection (LLND) in locally advanced lower rectal cancer remains controversial. This study is to compare total mesorectal excision (TME) with or without LLND in lower rectal cancer cases of stage II/III.MethodsThe electronic databases were systematically searched that compared TME with or without LLND among patients with lower rectal cancer in clinical stage II/III. Subgroup analysis was performed considering neoadjuvant chemoradiotherapy (nCRT). The hazard ratios (HR), relative risk (RR), and weighted mean difference (WMD) were pooled.ResultsTwelve studies of 4458 patients of this meta-analysis demonstrate, LLND alone significantly reduced the local recurrence rate of patients who did not receive nCRT (RR 0.71, P = 0.004), while the difference was not significant when combined with nCRT (RR 0.70, P = 0.36). The analysis shows TME with LLND was associated with significantly longer operation time (WMD 90.73 min, P < 0.001), more intraoperative blood loss (WMD 303.20 mL, P < 0.001), and postoperative complications (RR = 1.35, P =0.02). Whereas urinary dysfunction (RR 1.44, P = 0.38), sexual dysfunction (RR 1.41, P = 0.17), and postoperative mortality (RR = 1.52, P = 0.70), were similar between these two groups. Statistically, no significant differences were observed in OS (HR 0.93, P = 0.62), DFS (HR 0.99, P = 0.96), total recurrence (RR 0.98, P = 0.83), lateral recurrence (RR 0.49, P = 0.14), or distal recurrence (RR 0.95, P = 0.78) between these two groups regardless of whether nCRT was performed or not.ConclusionsThe study shows LLND alone decreases the local recurrence without using nCRT irrespective of the survival advantage in locally advanced lower rectal cancer. The benefit of controlling local recurrence by LLND alone makes us reconsider the usage of nCRT with LLND.Trial registrationThe protocol for this meta-analysis was registered prospectively with PROSPERO (CRD42020135575) on 16 May 2019.

Current and future cancer staging after neoadjuvant treatment for solid tumors.

Until recently, cancer registries have only collected cancer clinical stage at diagnosis, before any therapy, and pathological stage after surgical resection, provided no treatment has been given before the surgery, but they have not collected stage data after neoadjuvant therapy (NAT). Because NAT is increasingly being used to treat a variety of tumors, it has become important to make the distinction between both the clinical and the pathological assessment without NAT and the assessment after NAT to avoid any misunderstanding of the significance of the clinical and pathological findings. It also is important that cancer registries collect data after NAT to assess response and effectiveness of this treatment approach on a population basis. The prefix y is used to denote stage after NAT. Currently, cancer registries of the American College of Surgeons' Commission on Cancer only partially collect y stage data, and data on the clinical response to NAT (yc or posttherapy clinical information) are not collected or recorded in a standardized fashion. In addition to NAT, nonoperative management after radiation and chemotherapy is being used with increasing frequency in rectal cancer and may be expanded to other treatment sites. Using examples from breast, rectal, and esophageal cancers, the pathological and imaging changes seen after NAT are reviewed to demonstrate appropriate staging.

Comprehensive Analysis of ATP6V1s Family Members in Renal Clear Cell Carcinoma With Prognostic Values.

ATP6V1s participate in the biological process of transporting hydrogen ions and are associated with various cancers in expression and clinicopathological features, while its role in kidney renal clear cell carcinoma is unknown. We aimed to demonstrate the relationship between ATP6V1s and kidney renal clear cell carcinoma. This study investigated the expression and roles of ATP6V1s in KIRC using Oncomine, The Cancer Genome Atlas, UALCAN, Human Protein Atlas, Clinical Proteomics Tumor Analysis Consortium, GeneMANIA, Tumor IMmune Estimation Resource, GEPIA databases. Low mRNA and protein expression of ATP6V1s members were found to be significantly associated with clinical cancer stages, nodal metastasis status, and patient’s gender in KIRC patients. Besides, lower mRNA expression of ATP6V1A, ATP6V1B2, ATP6V1C1, ATP6V1C2, ATP6V1D, ATP6V1E1, ATP6V1E2, ATP6V1F, ATP6V1G1, and ATP6V1H have shorter OS. Taken together, these results indicated that ATP6V1s family members could be a potential target in the development of anti-KIRC therapeutics and an efficient marker of the prognostic value of KIRC.

Expression of TRPC1 and SBEM protein in breast cancer tissue and its relationship with clinicopathological features and prognosis of patients.

This study investigated the relationship of the expression of transient receptor potential channel 1 (TRPC1), small breast epithelial mucin (SBEM) in breast cancer tissues with clinical pathological features and prognosis of patients. Altogether 50 patients with breast cancer who were treated in Weifang People's hospital from April 2017 to November 2018 were selected, and the mRNA and protein differences of TRPC1 and SBEM in breast cancer patients and normal breast cancer tissues were detected by qRT-PCR and Western blot. Spearman test was used for correlation analysis. Logistic univariate and multivariate analysis were performed on the risk factors related to breast cancer metastasis in breast cancer patients. The expression of TRPC1 and SBEM in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.001). The mRNA expression of TRPC1, SBEM and protein was not related to age, tumor size and tissue grade of breast cancer patients, but related to TNM stage, clinical stage and lymph node metastasis (P<0.001). The relative expression of TRPC1 was positively correlated with clinical stage of breast cancer (r=0.992, P<0.001). The relative expression of SBEM was positively correlated with the clinical stage of breast cancer (r=0.853, P<0.001). The relative expression of TRPC1 was positively correlated with TNM staging of breast cancer (r=0.860, P<0.001). The relative expression of SBEM was positively correlated with TNM staging of breast cancer (r=0.880, P<0.001). Multivariate conditional Logistic regression analysis showed that TNM staging, TRPC1, SBEM were independent risk factors for malignant breast cancer metastasis. On the contrary, expression of TRPC1 and SBEM in breast cancer tissues was up-regulated. TRPC1 and SBEM may be involved in the process of breast cancer occurrence, development and metastasis, and can be used as potential tissue biomarkers in diagnosis of breast cancer metastasis and disease assessment.

Systemic analyses of expression patterns and clinical features for GIMAPs family members in lung adenocarcinoma.

GTPase of immunity-associated proteins (GIMAPs) are frequently prescribed as important components of immune regulation complexes, which were known to play key roles in lung adenocarcinoma. However, little is known about the function of distinct GIMAPs in lung adenocarcinoma. To address this issue, this study investigated the biological function and pathway of GIMAPs in lung adenocarcinoma using multiple public databases. Absent expression of GIMAPs was found in lung adenocarcinoma at mRNA and protein levels. While a purity-corrected value uncovered that all GIMAPs were positively associated with the immune infiltration of lung adenocarcinoma. Furthermore, the expressions of GIMAPs were considered to be negatively associated with clinical cancer stages, patient’s gender and pathological tumor grades in patients with lung adenocarcinoma. Besides, higher mRNA expression of GIMAPs was significantly associated with longer overall survival of patients with lung adenocarcinoma. Taken together, these results may enable GIMAPs family members as diagnostic and survival biomarker candidates or even potential therapeutic targets for patients with lung adenocarcinoma.

Extracapsular Extension Does Not Decrease Overall Survival in Rectal Cancer Patients with Lymph Node Metastasis Following Neoadjuvant Chemoradiotherapy

Background. The Tumor-Node-Metastasis system does not include additional prognostic factors present in the Lymph Node Metastasis (LNM) such as extra-capsular extension (ECE), which is associated with decreased survival. There are not studies addressing this topic in rectal cancer patients with preoperative chemoradiotherapy (nCRT) and total mesorectal excision (TME). Aim. We aimed to examine the survival influence of ECE in patients with stage III rectal cancer who received nCRT followed by surgery. Methods. A retrospective study of 126 patients prospectively collected with rectal cancer in clinical stage III rated with nCRT and TME from 2010 to 2015 was performed. Results. In total, 71.6% of cases had 1 to 3 lymph node metastases, most tumors were grade 2 (52.4%), 25.4% had good pathologic response, 77.8% had a good quality TME, and the median tumor budding count was 4/0.785 mm2. Forty-four (34.9%) patients had ECE+, which was associated with a higher nodal stage (pN2), perineural invasion and a higher lymph node retrieval. The factors associated with the survival were a higher pathologic T stage, higher pathological N stage, high-grade tumors, and perineural invasion. The ECE did not decrease the 5–year survival with a similar median survival (86.5 months for the ECE+ group vs. 84.1 for the ECE–). Conclusion. Our results demonstrate that ECE has no impact on overall survival in rectal cancer patients who received nCRT and this was independent of nodal stage or number of lymph nodes examined.

Effect of Breast Conserving Sentinel Lymph Node Biopsy (SLNB) and Modified Radical Mastectomy on Patients with Early Breast Cancer

Objective: To study the clinical effect of breast conserving combined with sentinel lymph node biopsy and modified radical mastectomy in patients with early breast cancer. Methods: Female patients with early breast cancer in clinical stage I and II were selected as the main objects of this study, the study period started from July 2017 to July 2020. In the breast conserving and sentinel lymph node biopsy patients, 50 cases were randomly selected as the experimental group; 50 cases in the modified radical mastectomy patients were randomly selected as the control group. The clinical intervention effect of the two groups was analyzed. Results: the perioperative indexes of the experimental group were shorter than those of the control group, the patients recovered faster, the incidence of complications in the experimental group was lower, and the quality of life scores of the experimental group were significantly higher than those of the control group, and the difference was statistically significant, the intervention effect of the experimental group was also better. Conclusion: The application of breast conserving and sentinel lymph node biopsy in the treatment of early breast cancer can promote the recovery of patients, shorten the operation time and reduce the rate of complications, which has significant clinical significance.

A Phase II Study on the Safety of Minimally Invasive Surgery Using Endoscopic Stapler to Prevent Tumor Spillage in Cervical Cancer

Study Objective The Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated that patients treated with minimally invasive surgery (MIS) techniques resulted in poorer outcomes than those treated with laparotomic techniques. In order to overturn the suggestion that MIS is inferior to laparotomic techniques, we designed and are now performing a phase II study on the safety of laparoscopic or robotic radical surgery using endoscopic stapler for inhibiting tumor spillage of cervical neoplasms (SOLUTION trial). Design A 42-year-old patient with cervical cancer clinical stage IB3 underwent robotic radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic sentinel lymphadenectomy with additional steps to improve surgical and morbidity outcomes. Setting In a Trendelenburg position, the patient is placed under general anesthesia. Patients or Participants This study is a prospective, multi-center phase II trial recruiting patients with early-stage cervical cancer. Interventions Key points of the operation are as follows: First, we perform tubal ligation and vaginal tube insertion, and then intracorporeal colpotomy using an endoscopic stapler to prevent tumor spillage into the peritoneal cavity. Second, we resected the stapled vaginal stump to retrieve the tumor specimen, and then close the vaginal stump again with continuous suture. Finally, we perform washing cytology three times: after trocar site insertion, intracorporeal colpotomy, and vaginal stump closure to check tumor spillage. Measurements and Main Results Ten patients so far have been enrolled in this study and all have received this surgery successfully without positive washing cytology, indicating no tumor spillage during the surgery. We plan to enroll a total of 120 patients within three years. Conclusion This is a feasible study design that can be performed with MIS, which is why it is valuable to prove its efficacy and safety through a phase II trial in order to overcome the limitations of MIS suggested in LACC trial. (SOLUTION ClinicalTrials.gov number, NCT04370496)

Disparities in advanced-stage breast cancer: The socioeconomic and geographic contributions.

134 Background: Socioeconomic disparities in healthcare have been well documented in America, with cancer being a critical area. One in four deaths are caused by cancer, and the effects on different communities are not equal. Clinical observations suggest that poorer socioeconomic circumstances lead to more frequent, later stage diagnoses and worse outcomes. The aim of this project was to quantify the sociodemographic and geographic contributions to disparities in advanced, metastatic breast cancer within the Augusta population and surrounding areas. Methods: Records of patients managed for breast cancer at the Georgia Cancer Center between Jan 2009- Jun 2019 were reviewed. 80 patients who presented with early stage breast cancer (clinical stage I) without positive lymph nodes were compared with 80 patients who presented with advanced, metastatic disease (clinical stage III-IV). Their race, breast cancer characteristics, insurance status, geographic proximity to a mammography site or major healthcare facility, and time interval between diagnosis and treatment were compared. Results: Results show that 73.75% early stage patients had private insurance, while 41.25% late stage patients had private insurance (p value &lt; 0.0001). Results also show that 25.0% of late stage patients had annual mammography screenings, while 77.78% of early stage patients had regular screening for mammograms (p value &lt; 0.0001). 80.6% of patients that received regular mammograms had private insurance, while the remaining 19.4% of those patients had public insurance. No statistical difference was shown in late and early stage presentation based on HER2 and/or triple negative (ER-, PR-, HER2-) status. Conclusions: There is a significant outcome of advanced, metastatic breast cancer in patients that do not have private insurance and in those that do not receive regular mammograms. Our findings support the importance of investing resources into alleviating differences in various socioeconomic populations as they relate to the amount and quality of cancer healthcare available. While the incidence of mortality in breast cancer is decreasing nationwide, disparities in morbidity and mortality will most likely continue unless there is an aggressive effort towards addressing said differences.

The Academic Facility Is Associated with Higher Utilization of Esophagectomy and Improved Overall Survival for Esophageal Carcinoma

BackgroundOperable esophageal carcinoma is potentially curable with surgical resection. The short-term outcomes and overall survival rate for operable esophageal carcinoma may be impacted by the healthcare facility type where patients receive care. MethodsA total of 37, 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Data Base at over 12,721 facilities were analyzed. Healthcare facilities were dichotomized into the community and academic facility types. Marginal multivariable Cox proportional hazard models were used to evaluate differences in overall survival between facility types, which accounted for facility esophageal cancer volume. Propensity score methodology with inverse probability of treatment weighting was used to adjust for patient related baseline differences between facility types. ResultsPatients with clinical stage I–III esophageal carcinoma who underwent esophagectomy at academic healthcare facilities had a significantly better overall survival compared with patients who underwent esophagectomy at community healthcare facilities [HR = 0.89: CI [0.84–0.95] (p = 0.0005)]. The rate of esophagectomy was significantly higher at the academic facilities (49.0% versus 26.5%; p < 0.0001). The 30-day and 90-day mortality rates for esophagectomy were significantly better for patients who underwent esophagectomy for esophageal cancer at the academic facility types. ConclusionPatients with clinical stage I–III esophageal carcinoma who received care at academic facility types had significantly better overall survival compared with community facility types. The utilization of esophagectomy was significantly higher and the short-term surgical outcomes were better for patients treated at academic facility types.

Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy.

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). Methods: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. Results: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. Conclusions: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.

151 Poster - Role of miR-21 in chemotherapeutic drug resistance of oral squamous cell carcinoma

Background: Head and neck carcinoma spreads malignancies tumors arising from the epithelium or squamous covering the upper aerodigestive tract including oral that metastasize to other organs. The oral squamous cell carcinoma primarily addressing Head and neck carcinoma cancer that could affect the majority of older people with approximately 650,000 new cases per year. The consumption of alcohol and tobacco might be the prime cause of OSCC risk. But the recurrence or relapse of the malignancies is the major obstacle of the convention chemotherapeutic drug like paclitaxel or carboplatin. We know the circulating miRNAs is noted as the potential biomarkers of OSCC but their role in drug resistance is yet to reveal. In the present study, an attempt made to find the expression of miR-21 in serum/ whole blood of relapse OSCC (rOSCC) and newly identified OSCC (nOSCC) (N = 40). The expression of miR-21 was evaluated in relation to different demographical and clinicopathological features aiming to identify correlation with relapse and their cancer clinical stages (perineural invasion and N-stage).

Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

Circular RNA (circRNA) is an endogenous noncoding RNA. Accumulative investigations have confirmed that circRNAs play a vital role in carcinogenesis and tumor progression. Herein, we examined the expression and mechanism of circ_0072088 in esophageal squamous cell carcinoma (ESCC). As a result, circ_0072088 was significantly overexpressed in ESCC tissues and cells, which was closely associated with tumor size, invasion depth, clinical stage, and lymph node metastasis of esophageal cancer. Nuclear and cytoplasmic separation as well as FISH assays showed that circ_0072088 was mainly localized in the cytoplasm of ESCC cells. RNase R treatment assay revealed that circ_0072088 was steadier than linear ZFR mRNA. circ_0072088 promoted ESCC cell proliferation, migration and invasion in vitro, and cell proliferation in vivo. Mechanistically, circ_0072088 upregulated VEGF gene expression by acting as the sponge of miRNA-377. In conclusion, circ_0072088 might be used as a diagnostic biomarker and therapeutic target for ESCC.

Forkhead box P3 promotes breast cancer cell apoptosis by regulating programmed cell death 4 expression.

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer apoptosis remain unclear. To investigate the underlying genes and networks regulated by FOXP3 in breast cancer, RNA sequencing was performed to compare FOXP3-overexpressing MDA-MB-231 cells and control MDA-MB-231 cells. Differentially expressed genes were identified, and functional enrichment analysis comparing the two groups was performed. The differentially expressed genes were mainly enriched in phagosomes, oxytocin, serotonergic synapses and the phospholipase D signaling pathway. Furthermore, gene set enrichment analysis revealed the enrichment of a gene signature associated with apoptosis in FOXP3-overexpressing MDA-MB-231 cells compared with wild-type cells. Further analysis showed that programmed cell death 4 (PDCD4), a key molecule involved in apoptosis, was overexpressed in FOXP3-MDA-MB-231 cells. Reverse transcription-quantitative PCR and western blotting showed that FOXP3 upregulated the expression of PDCD4 in breast cancer cells. Clinical sample analysis using a public database showed that the expression level of PDCD4 was associated with breast cancer clinical stages. Overall, the present study suggested that FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

Upregulation of CCT-3 Induces Breast Cancer Cell Proliferation Through miR-223 Competition and Wnt/β-Catenin Signaling Pathway Activation.

The clinical significance and the function of chaperonin-containing TCP1 complex 3 (CCT-3) in breast cancer remain unknown. In this study, we found that CCT-3 was markedly overexpressed in breast cancer tissues. Statistical analysis revealed a significant correlation of CCT-3 expression with advanced breast cancer clinical stage and poorer survival. Ablation of CCT-3 knocked down the proliferation and the tumorigenicity of breast cancer cells in vitro and in vivo. CCT-3 may regulate breast cancer cell proliferation through a ceRNA network between miR-223 and β-catenin, thus affecting Wnt/β-catenin signaling pathway activation. We also validated that CCT-3 and β-catenin are novel direct targets of tumor suppressor miR-223. Our results suggest that both mRNA and the protein levels of CCT-3 are potential diagnosis biomarkers and therapeutic targets for breast cancer.

Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial

Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing. Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group). In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile. F Hoffmann-La Roche/Genentech.

BRD4/8/9 are prognostic biomarkers and associated with immune infiltrates in hepatocellular carcinoma.

Bromodomain (BRD)-containing proteins are a class of epigenetic readers with unique recognition for N-acetyl-lysine in histones and functions of gene transcription and chromatin modification, known to be critical in various cancers. However, little is known about the roles of distinct BRD-containing protein genes in hepatocellular carcinoma (HCC). Most recently, we investigated the transcriptional and survival data of BRD1, BRD2, BRD3, BRD4, BRD7, BRD8, BRD9 in HCC patients through ONCOMINE, UALCAN, Human Protein Atlas, GEPIA, cBioPortal, STRING, TIMER databases. BRD1/2/3/4/7/8/9 were over-expressed in HCC and were significantly associated with clinical cancer stages and pathological tumor grades. High mRNA expressions of BRD4/8/9 were promising candidate biomarkers in HCC patients. The rate of sequence alternations in BRD1/2/3/4/7/8/9 was relatively high (52%) in HCC patients, and the genetic alternations were correlated with shorter overall survival and disease-free survival in HCC patients. Additionally, the mRNA expression levels of individual BRD genes were significantly positively associated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. And the associations between BRD1/2/3/4/7/8/9 and diverse immune marker sets showed a significance. Overall, these results indicated that BRD4/8/9 could be potential prognostic markers and druggable epigenetic targets in HCC patients.