Squamous Carcinoma Patients Research Articles

Secondary primary lung cancer after esophageal cancer: a population-based study of 44,172 patients

Background The present study aimed to assess the survival, incidence, and characteristics of secondary primary lung cancer (SPLC) after esophageal cancer (EC-LC). Methods The patients with esophageal cancer (EC) who developed SPLC and patients with first primary lung cancer (LC-1) were retrospectively reviewed in the Surveillance, Epidemiology, and End Results 18 registries covering 2000–2016. Overall survival and characteristics were compared between patients with EC-LC and patients with LC-1. The independent relation between a history of EC and death was evaluated by calculating hazard ratios in multivariate Cox regression analysis propensity score-matching analysis, and multiple imputation for cases with missing information. Results In comparison with the general population, the patients with EC had a higher risk for developing secondary primary lung cancer (SIR =1.86, 95% confidence interval (CI): 1.69–2.05). A history of EC was found to be an independent risk factor of death for lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients in localized stage based on multivariate Cox regression analysis, propensity score-matching analysis and multiple imputation. Conclusions There is a significantly increased risk of secondary primary lung cancer in EC survivors and a history of EC adversely affects overall survival in individuals who subsequently develop localized LUSC and LUAD. Clinicians should moderately strengthen lung tissue protection during the management of EC patients.

Comparison of PD-1 Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma in the Second-Line Setting.

BackgroundKEYNOTE-181, ATTRACTION-3, and ESCORT trials have opened the era of programmed death 1 (PD-1) inhibitors in the second-line therapy for esophageal squamous cell carcinoma (ESCC). There is no head-to-head comparison of pembrolizumab vs. nivolumab vs. camrelizumab in the second-line setting for ESCC. We performed an indirect comparison to explore the optimal choice of immune checkpoint inhibitor (ICI) for advanced ESCC.MethodsPatients in ATTRACTION-3 and ESCORT were all squamous carcinoma, while KEYNOTE-181 enrolled both adenocarcinoma and squamous carcinoma patients. We only extract information of patients with squamous carcinoma from KEYNOTE 181 study and all the patients from ATTRACTION-3 and ESCORT. The main clinical outcomes for this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).ResultsIndirect analysis showed similar survival benefit among three PD-1 inhibitors. Nivolumab was comparable with pembrolizumab in most subgroups except that nivolumab was slightly better for patients with performance status (PS) score of 1 [HRnivo/pembro: 0.68 (95% confidence interval (CI): 0.45–1.02], p = 0.07). Compared with nivolumab indirectly, pembrolizumab and camrelizumab had better PFS [HRpembro/nivo: 0.85 (95% CI: 0.63–1.14), p = 0.29; HRcam/nivo: 0.64 (95% CI: 0.47–0.87), p = 0.004] and significantly higher ORR [RRpembro/nivo: 2.51 (95% CI: 1.22–5.15), p = 0.01; RRcam/nivo: 3.52 (95% CI: 1.73–7.18), p = 0.001]. Compared with camrelizumab indirectly, pembrolizumab had slightly worse PFS [HRpembro/cam: 1.33 (95% CI: 0.99–1.79), p = 0.057] and comparable ORR [RRpembro/cam: 0.71 (95% CI: 0.32–1.60; p = 0.41)]. Camrelizumab had a significantly higher rate of all grade TRAEs than both pembrolizumab and nivolumab.ConclusionsCombining the safety and potential survival benefit, we recommend nivolumab for ESCC patients with PS score of 1 and pembrolizumab or camrelizumab for patients with better PS and seeking for higher efficacy or longer PFS.

CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1.

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.

Predictive modelling of level IIb lymph node metastasis in oral squamous cell carcinoma

The aim of the present study was to examine the conditions, characteristics, and risk factors of level IIb lymph node metastases in oral squamous cell carcinoma and to formulate surgical criteria for level IIb lymph node dissection. We analyzed clinical and pathological records for 541 oral squamous carcinoma patients in relation to level IIb metastasis. Univariate and multivariate analyses were performed to detect risk factors for level IIb lymph node metastasis; a predictive model was built based on multivariate analysis and tested in a validation group. Univariate and multivariate analyses using the training group indicated that level IIa metastasis and Lymphovascular permeation (LVP) were two independent risk factors for level IIb lymph node metastasis. This model was built and tested in a validation group, the area under the curve being 0.697 (P < .0.001). The model’s sensitivity was 66.7% and specificity was 77.4%. Nomogram incorporating validated variables was developed for level IIb metastasis prediction. Expected survival probabilites were analysed to specify significance of model's variable on patients’ overall survival and recurrence. Level IIb dissection should be performed in patients with level IIa metastasis and LVP. However, thorough consideration of the oncologic safety of omitting level IIb dissection is compulsory.

Distinct roles of miR-34 family members on suppression of lung squamous cell carcinoma

miR-34, whose mimic was used on phase I clinical trial, has been extensively reported since its dysfunction in various cancers including non-small-cell lung cancer (NSCLC). However, the roles of miR-34 family members in the progression of lung squamous carcinoma (SCC) in patients who have occupational-exposure experience are unclear yet. Here, we comprehensively investigated the expression levels of miR-34 family members in SCC patients and compared the roles of them in SCC in vitro and vivo. The results showed that the average levels of miR-34a and miR-34b/c were decreased in patients. The analysis of miR-34a to miR-34b/c levels in patients graded different stages or metastases or recurrence showed that miR-34b/c was reduced earlier and more significantly than miR-34a. In vitro assays demonstrated that both miR-34a and miR-34b/c inhibits SCC cells proliferation, migration and invasion via Notch1 pathway, while miR-34b/c effects more than miR-34a does. As miR-34a was significantly decreased in cancer recurrence, the further analysis of relationship between miR-34a and stem cell adhesion molecular CD44 showed that miR-34a was significantly correlated with CD44 levels in patients. Knockdown of CD44 significantly blocked miR-34a mediated inhibition of cell migration and invasion. Treating the purified CD44hi cells with miR-34 overexpression lentivirus inhibited the tumor outgrowth. By contrast, anti-miR-34 facilitated tumor development of CD44low cells. Our study showed that miR-34 family members are negative regulator for SCC development, even though the inhibition is mediated by multiple and complicated signal pathways, which provides theoretical basis for SCC treatment and a biomarker candidate for SCC prognosis.

FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells

BackgroundAngiogenesis is the process by which new blood vessels arise from pre-existing ones. Fibroblast growth factor-2 (FGF-2), a leading member of the FGF family of heparin-binding growth factors, contributes to normal as well as pathological angiogenesis. Pre-mRNA alternative splicing plays a key role in the regulation of cellular and tissular homeostasis and is highly controlled by splicing factors, including SRSFs. SRSFs belong to the SR protein family and are regulated by serine/threonine kinases such as SRPK1. Up to now, the role of SR proteins and their regulators in the biology of endothelial cells remains elusive, in particular upstream signals that control their expression.ResultsBy combining 2D endothelial cells cultures, 3D collagen sprouting assay, a model of angiogenesis in cellulose sponges in mice and a model of angiogenesis in zebrafish, we collectively show that FGF-2 promotes proliferation, survival, and sprouting of endothelial cells by activating a SRSF1/SRSF3/SRPK1-dependent axis. In vitro, we further demonstrate that this FGF-2-dependent signaling pathway controls VEGFR1 pre-mRNA splicing and leads to the generation of soluble VEGFR1 splice variants, in particular a sVEGFR1-ex12 which retains an alternative last exon, that contribute to FGF-2-mediated angiogenic functions. Finally, we show that sVEGFR1-ex12 mRNA level correlates with that of FGF-2/FGFR1 in squamous lung carcinoma patients and that sVEGFR1-ex12 is a poor prognosis marker in these patients.ConclusionsWe demonstrate that FGF-2 promotes angiogenesis by activating a SRSF1/SRSF3/SRPK1 network that regulates VEGFR1 alternative splicing in endothelial cells, a process that could also contribute to lung tumor progression.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

IntroductionComprehensive updated information on cervical cancer surgical treatment in Europe is scarce.ObjectiveTo evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality...

Clinical outcomes, prognosis, and predictors of salvage surgery in oral cavity squamous cell carcinoma.

e18040 Background: Salvage surgery (SS) is one of the curative options for oral cavity squamous cell carcinoma (OCSCC) patients with locoregional recurrence (LRR) or secondary primary, but the role of SS should be reevaluated between life expectancy, morbidity, and quality of life. Selecting suitable OCSCC patients receiving SS is important. Methods: From 2010 to 2018, newly diagnosed OCSCC patients who progressed to LRR or secondary primary were recorded. Clinical outcomes, prognostic factors, and predictors were analyzed for the patients receiving SS. Cox regression analyses were performed for PSS, defined from the date of SS to the date of death or last follow-up. Survival was estimated using the Kaplan–Meier method and log-rank tests. Results: A total of 263 newly diagnosed OCSCC patients progressing to LRR or secondary primary were recorded. Half (55.1%, 145/263) of them received SS, and one-third (29.7%, 43/145) of the SS group received twice and more times SS. Median survivals after disease progression were 65.6 and 10.6 months for patients with or without SS, respectively (P &lt; 0.001). A total of 214 SS events were enrolled for analysis. Nearly twenty percentage (20.1%, 39/194) of SS events would progress to death within 1 year after surgery (PSS &lt; 1 year). PSSs of the first, secondary, third, and fourth or more times SS were 64.2, 47.6, 40.9, and 18.9 months, respectively (P = 0.217). Surgical features of the last surgery (perineural invasion and depth of invasion), the interval between the last and current surgery, and clinical N staging of the current surgery were the four independent factors for PSS. To predict the patients with PSS &lt; 1 year, a scoring system was established that each of the independent factors was scored one point. The area under the curve of the scoring system was 0.755, and sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 76.0%, 39.0%, and 90.8%, respectively (Table). Conclusions: A scoring system with a high negative predictive value was established to predict PSS &lt; 1 year.[Table: see text]

Thyroid hormone receptor α1 acts as a new squamous cell lung cancer diagnostic marker and poor prognosis predictor: Can it be a novel therapeutic target?

e20508 Background: Lung cancer is considered the first cause of cancer-related death worldwide. Unfortunately, all therapeutic regimens used in lung cancer treatment showed relatively equivalent efficacy. The search and subsequent testing of new therapeutic targets that can be used alternative to, after the failure of or in association with the currently used therapeutics to improve the prognosis is an urgent demand and consequently a very interesting era of oncological lung research. Up to date, it is known that Thyroid hormones and Thyroid hormone receptors (THRs) controls many tumors progression, nevertheless, its role in non-Small Cell Lung cancer (NSCLC) is not yet defineltly understood. This study investigated the expression of Thyroid hormone receptor alpha 1 (THRα1) in NSCLC cases. Methods: Immunohistochemistry using THRα1 antibody was performed on tissue sections collected from 80 patients diagnosed with NSCLC. We also analyzed the expression of THRα gene in Microarrays of squamous cell lung carcinoma (SCC) and adenocarcinoma (AC) patients by using GEO datasets on https://www.ncbi.nlm.nih.gov. Results: We showed, for the first time, the expression of THRa1 in NSCLC. Intermediate and high THRa1 expression was detected in (25% and 66.7%) of SCC cases respectively. High THRa1 expression was associated with shorter OS and poor prognosis. On the other hand, 86.7% of AC cases revealed low THRa1expression. By analyzing GEO data sets, a significant increase in THRa gene value was found in SCC compared to AC cases. Inflammatory cells in SCC cases showed high THRα1 expression. Conclusions: Our study is shedding a new light on the relevance of THRα1 in lung cancer not only as a possible prognostic marker but also as an innovative diagnostic additive tool for lung squamous cell carcinoma which could be tested as a therapeutic target as well.

Neoadjuvant PD-1 blockade combined with chemotherapy followed by concurrent immunoradiotherapy for locally advanced anal canal squamous carcinoma patients: Antitumor efficacy, safety and biomarker.

e15500 Background: Efficacy and safety of PD-1 inhibitors have been approved for the treatment of metastatic anal squamous cancer patients, but the efficacy of neoadjuvant treatment with PD-1 in anal squamous cancer patients has not yet been defined. We report results for the cohort of patients with locally advanced anal canal squamous carcinoma treated with neoadjuvant PD-1 inhibitor toripalimab and chemotherapy followed by concurrent immunoradiotherapy. Methods: Five locally advanced anal canal squamous carcinoma patients received 4 cycles of neoadjuvant PD-1 inhibitor toripalimab and Docetaxol and Cisplatin chemotherapy followed by concurrent immunoradiotherapy. Whole exome sequencing (WES) and mIHC were performed with the pretreatment tumor tissue for biomarker analysis. Results: Complete clinical response (cCR) was achieved in 4 patients after neoadjuvant treatment before radiotherapy while the other patient achieved near cCR. cCR was achieved in all the 5 patients 3 months after definitive immunoradiotherapy. Grade 3 toxicity was noted in 1 patient. Molecular testing revealed that PD-L1 expression (≥1%) in tumor and CD4/CD163 expression in tumor and paracancerous tissue were positively correlated with tumor shrinkage in the neoadjuvant treatment phase while TMB didn’t appear to significantly impact the response. Conclusions: PD-1 inhibitor combined with chemoradiotherapy has quite promising effect in locally advanced anal canal squamous carcinoma patients, with very mild toxicity. Pretreatment PD-L1 expression is positively correlated with tumor response to PD-1 inhibitor toripalimab and chemotherapy. It is worthy of further investigation in prospective clinical trial.

Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Cervical cancer is one of the most malignant reproductive diseases seen in women worldwide. The identification of dysregulated genes in clinical samples of cervical cancer may pave the way for development of better prognostic markers and therapeutic targets. To identify the dysregulated genes (DEGs), we have retrospectively collected 10 biopsies, seven from cervical cancer patients and three from normal subjects who underwent a hysterectomy. Total RNA isolated from biopsies was subjected to microarray analysis using the human Clariom D Affymetrix platform. Based on the results of principal component analysis (PCA), only eight samples are qualified for further studies; GO and KEGG were used to identify the key genes and were compared with TCGA and GEO datasets. Identified genes were further validated by quantitative real-time PCR and receiver operating characteristic (ROC) curves, and the highest Youden index was calculated in order to evaluate cutoff points (COPs) that allowed distinguishing of tissue samples of cervical squamous carcinoma patients from those of healthy individuals. By comparative microarray analysis, a total of 108 genes common across the six patients' samples were chosen; among these, 78 genes were upregulated and 26 genes were downregulated. The key genes identified were SPP1, LYN, ARRB2, COL6A3, FOXM1, CCL21, TTK, and MELK. Based on their relative expression, the genes were ordered as follows: TTK > ARRB2 > SPP1 > FOXM1 > LYN > MELK > CCL21 > COL6A3; this generated data is in sync with the TCGA datasets, except for ARRB2. Protein-protein interaction network analysis revealed that TTK and MELK are closely associated with SMC4, AURKA, PLK4, and KIF18A. The candidate genes SPP1, FOXM1, LYN, COL6A3, CCL21, TTK and MELK at mRNA level, emerge as promising candidate markers for cervical cancer prognosis and also emerge as potential therapeutic drug targets.

TTN/TP53 mutation might act as the predictor for chemotherapy response in lung adenocarcinoma and lung squamous carcinoma patients.

BackgroundChemotherapy is the preferred treatment in many types of cancer including lung cancer. However, most of patients resist chemotherapy resulting in disease progressive and recurrence. Titin (TTN) mutation is proved as a beneficial role in lung squamous carcinoma (LUSC), but the predictive role on chemotherapy resistance of lung cancer is still limited and discussable.MethodsClinical information and related somatic mutation profiles were obtained from The Cancer Genome Atlas (TCGA) database and analyzed by R-Studio using R-package. Overall survival (OS) curve and the association between gene mutation and clinical features were determined by GraphPad 6.0 software.ResultsAvailable data including 563 lung adenocarcinoma (LUAD) and 505 LUSC subjects were included in this study. Among all patients, 205 out of 563 LUAD and 326 out of 505 LUSC patients displayed TTN gene mutation. When comparing the clinical features in TTN-mutated patients to patients without TTN mutation who received chemotherapy, the tumors were always located in the upper lung in LUAD patients with TTN mutation and most of TTN-mutated subjects were at low pathological stage, which was not observed in LUSC patients. However, patients with TTN-mutation, particularly missense mutation, had a higher chemosensitivity and longer OS period than that patients without TTN mutation in both LUAD and LUSC. Of note, LUAD and LUSC patients possessed favorable OS and better chemotherapy response benefiting from TTN/tumor protein 53 (TP53) double mutation compared to TTN and TP53 mutation alone, respectively. Additionally, TTN/TP53 double mutation-initiated high rate of chemotherapy response were largely concentrated within LUAD and LUSC patients whose anatomic neoplasm subdivision were located in the upper lung.ConclusionsCollectively, TTN/TP53 co-mutation is possibly served as an effective predictor for OS and chemotherapy response in lung cancer.

Results of radiotherapy in squamous cell laryngeal cancer: A tomotherapy center experience.

Laryngeal cancer is a common type of head and neck cancer (HNC). Radiotherapy (RT) is a mainstay for curative treatment. Intensity-modulated RT (IMRT) is a standard technique today, as it provides of higher survival and local control and lower normal tissue toxicity. One of IMRT devices is helical tomotherapy (HT). The HT treatment results of HNC patients have been reported in few studies. We aimed to investigate the results of squamous cell laryngeal carcinoma patients treated with helical tomotherapy. Forty-five laryngeal cancer patients were selected according to the inclusion criteria. Radiotherapy (RT) plans were set in the Hi-Art HT planning system. Image-gated RT (IGRT) technique was used. Appropriate patients received simultaneous cisplatin. Treatment response rates were evaluated at the post-RT third and sixth months. Survival times were calculated with the Kaplan-Meier method. The factors affecting the treatment results were evaluated using Log-rank and Cox regression tests. A P value of less than 0.05 was accepted as statistically significant. The median age was 65 (28-84) years. The median symptom duration was 6 (1-60) months. The RT dose for the early and the locally advanced disease was median 63 Gy (60.75-66) and 66 Gy (60-70), respectively. The RT interruption was median two (0-20) days. The patients were followed up to 25 (1-45) months. Grade 2 xerostomia and dysphagia rates were 55% and 7%, respectively. The 3-year estimates of overall survival (OS), disease-free survival (DFS), metastasis-free survival (DMFS), and locoregional recurrence-free survival (RRFS) were 71.7%, 60.4%, 84.9%, and 68.5%, respectively. In univariate analysis, the presence of N2 disease was a negative prognostic for DFS (P = 0.05) and DMFS (P = 0.003). RT interruption >2 days was a negative prognostic for OS (P = 0.005), DFS (P = 0.02), and RRFS (P = 0.023). In the multivariate analysis, symptom duration >6 months was found to be the only significant factor for DFS (P < 0.05). Intensity-modulated radiation with HT achieved comparable clinical outcomes with acceptable toxicity in laryngeal carcinoma.

CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer.

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra‐deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor‐positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell‐free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C‐terminal domain. Using a gene‐editing approach in a luminal breast cancer cell line, MCF‐7, we observed that the expression of p27kip1 truncating mutants that lose the C‐terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C‐terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Identification of a novel subpopulation of Caspase-4 positive non-small cell lung Cancer patients

BackgroundTherapy/prognosis of Non-Small Cell Lung Cancer (NSCLC) patients are strongly related to gene alteration/s or protein expression. However, more than 50% of NSCLC patients are negative to key drugable biomarkers.MethodsWe used human samples of NSCLC and mouse models of lung adenocarcinoma.ResultsWe showed that caspase-4 was highly present in the tumor mass compared to non-cancerous human tissues. Interestingly, the orthologue murine caspase-11 promoted lung carcinogenesis in mice. Carcinogen-exposed caspase-11 knockout mice had lower tumor lesions than wild type mice, due to the relevance of caspase-11 in the structural lung cell as demonstrated by bone marrow transplantation and adoptive transfer experiments. Similarly to what observed in mice, caspase-4 was correlated to the stage of lung cancer in humans in that it induced cell proliferation in a K-Ras, c-MyC and IL-1α dependent manner. Caspase-4 positive adenocarcinoma (79.3%) and squamous carcinoma (88.2%) patients had lower median survival than patients who had lower levels of caspase-4. Moreover, PD-L1 expression and gene mutation (i.e. EGFR) were not correlated to caspase-4 expression. Instead, NSCLC patients who had K-Ras or c-MyC gene alteration were positively correlated to higher levels of caspase-4 and lower survival rate.ConclusionsWe identified a subgroup of NSCLC patients as caspase-4 positive among which double and triple positive caspase-4, K-Ras and/or c-MyC patients which prognosis was poor. Because K-Ras and c-MyC are still undrugable, the identification of caspase-4 as a novel oncoprotein could introduce novelty in the clinical yet unmet needs for NSCLC patients.

Localized fluorescent imaging of multiple proteins on individual extracellular vesicles using rolling circle amplification for cancer diagnosis.

Extracellular vesicles (EV) have attracted increasing attention as tumour biomarkers due to their unique biological property. However, conventional methods for EV analysis are mainly based on bulk measurements, which masks the EV‐to‐EV heterogeneity in tumour diagnosis and classification. Herein, a localized fluorescent imaging method (termed Digital Profiling of Proteins on Individual EV, DPPIE) was developed for analysis of multiple proteins on individual EV. In this assay, an anti‐CD9 antibody engineered biochip was used to capture EV from clinical plasma sample. Then the captured EV was specifically recognized by multiple DNA aptamers (CD63/EpCAM/MUC1), followed by rolling circle amplification to generate localized fluorescent signals. By‐analyzing the heterogeneity of individual EV, we found that the high‐dimensional data collected from each individual EV would provide more precise information than bulk measurement (ELISA) and the percent of CD63/EpCAM/MUC1‐triple‐positive EV in breast cancer patients was significantly higher than that of healthy donors, and this method can achieve an overall accuracy of 91%. Moreover, using DPPIE, we are able to distinguish the EV between lung adenocarcinoma and lung squamous carcinoma patients. This individual EV heterogeneity analysis strategy provides a new way for digging more information on EV to achieve multi‐cancer diagnosis and classification.

ACOT11 promotes cell proliferation, migration and invasion in lung adenocarcinoma.

BackgroundLung cancer is one of the most common cancers in the word. However, the underlying mechanism remains largely unknown. ACOT11 encodes enzymes hydrolyzing the fatty acyl-CoA esters into free fatty acids and CoA. Besides from its role in fatty acid metabolism, the other aspects regarding its function in the progression of lung cancer have not been revealed.MethodsWe first explored the clinical profile of ACOT11 in tumor samples. Next, we combined gene knockdown in vitro and in vivo and microarray gene profiling analysis to decipher the unknown regulatory role of ACOT11 in lung cancer carcinoma. Furthermore, we explored the potential molecular mechanisms of ACOT11 with immunoprecipitation.ResultsWe found high expression of ACOT11 in tumor samples. High expression of ACOT11 showed significantly poor prognosis in lung squamous carcinoma (LUSC) patients. Knocking down of ACOT11 inhibited the cell proliferation, migration as well as invasion in vitro and in vivo. It also promoted the cell apoptosis and cell cycle arrest via multiple signaling pathways. Additionally, ACOT11 could bind with CSE1L, which was proved to be an oncogene in lung cancer and speculated to be a potential target of ACOT11.ConclusionsThe results revealed that ACOT11 regulates proliferation, migration and invasion of lung cancer carcinoma via multiple signaling pathways, indicating its potential value in molecular therapy.

Serum lncRNAs (CCAT2, LINC01133, LINC00511) with Squamous Cell Carcinoma Antigen Panel as Novel Non-Invasive Biomarkers for Detection of Cervical Squamous Carcinoma.

BackgroundWe screened long non-coding RNAs (lncRNAs) specifically expressed in the serum of cervical squamous carcinoma (CESC) patient samples and investigated the role of these specific lncRNAs in the diagnosis of CESC and cervical intraepithelial neoplasia (CIN).MethodsThe expression levels of the lncRNAs CCAT2, LINC01133, and LINC00511 in the serum of normal controls and patient with CESC and CIN were measured using reverse transcription–quantitative polymerase chain reaction (RT-qPCR). Next, we analyzed the correlation between the serum lncRNAs levels and the clinical characteristics of CESC. Thereafter, we estimated their combined diagnostic value by receiver operating characteristic (ROC) curve analysis.ResultsThe results showed that CCAT2, LINC01133, and LINC00511 were highly expressed in the serum of patients with CESC. When these lncRNAs and squamous cell carcinoma (SCC) antigen were combined, the area under the ROC curve (AUC) value reached 0.94. We also found that the AUC value of the diagnostic model combining CCAT2 and LINC01133 reached 0.894.ConclusionThe serum lncRNAs (CCAT2, LINC01133, and LINC00511) and SCC may be new non-invasive biomarkers for the diagnosis of CESC.

A multicenter, single-arm, basket design, phase II study of NC-6004 plus gemcitabine in patients with advanced unresectable lung, biliary tract, or bladder cancer.

NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patients. All patients received 135 mg/m2 NC-6004 on day one and 1,250 mg/m2 gemcitabine on days one and eight. The median progression-free survival was 3.9 months in NSCLC patients, 4.3 months in biliary tract cancer patients, and 6.8 months in bladder cancer patients fit for cisplatin treatment. The most frequently reported Grade 3 Treatment Emergent Adverse Events across all cohorts were nausea, anemia and neutropenia, and hyponatremia. Quality of life measures for patients who received the combined therapy were generally consistent with expectations for patients undergoing chemotherapy. Overall, combined NC-6004 and gemcitabine treatment resulted in long-lasting antitumor activity and had a favorable safety profile, suggesting that it should be investigated further as a therapy for various types of cancer.

Incidence and impact of dysplasia at final resection margins in cancers of the oral cavity

Background The literature often cites margin status as being free, close or involved by tumor but there is very sparse evidence of the relevance of dysplasia at resection margin. Aims/Objectives: To compare the impact of dysplasia at final resection margin (D-FRM) and other margin statuses on overall survival (OS) and disease free survival (DFS). Methods This is a retrospective review of 1700 treatment naïve oral squamous carcinoma patients who underwent surgery between January 2012 and December 2015. The study arm consisted of patients with dysplasia at final resection margin (D-FRM). Each of these patients were double propensity matched to obtain positive (P-FRM), close (C-FRM) and free final resection margins (F-FRM). Results There was no hazard discrimination in survival among the D-FRM and C-FRM (vs F-FRM; p-0.597, HR-1.207 (0.621–2.346) and p-0.075, HR-1.594 (0.947–2.684), respectively). A decreasing survival trend was observed as the grade and number of D-FRM margins increased. Although not significant, the addition of adjuvant therapy for D-FRM showed a trend towards improved survival outcomes compared to C-FRM, especially with chemotherapy. Conclusion and relevance: The presence of D-FRM, irrespective of grade, had a similar impact on survival as C-FRM and underscores the possible need for treatment intensification.