A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation.

BACKGROUND: Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. METHODS: We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. RESULTS: We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. CONCLUSION: We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

RAB27A promotes the proliferation and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types worldwide. Despite significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and has been reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited proliferation and clone formation of SW480 colon cancer cells, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A is identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.

Homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to nivolumab in a patient with lung adenocarcinoma: a case report.

Immune checkpoint inhibitors (ICIs) have greatly improved the treatment of advanced non-small-cell lung cancer, including lung adenocarcinoma (LUAD). Patients treated with ICIs can have long-term clinical outcomes; however, acquired resistance to ICI therapy has been frequently observed. To date, little is known about the underlying mechanisms. In this study, we report the case of a male smoker with metastatic LUAD who initially received multi-line radiotherapy and chemotherapy and achieved stable disease (SD) for almost 10 years. The patient was treated with nivolumab for about 15 months. However, the disease later progressed rapidly. A genetic profile of the patient revealed the homozygous deletion of the human leukocyte antigen (HLA)-B gene, which may have conferred the acquired resistance. Our study is the first to describe the homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to programmed cell death protein 1 (PD-1) blockade in a patient with LUAD. This evidence suggests that tumor cells can selectively lose HLA-A, B, and C to survive under strong immune pressure. This discovery enriches and develops our understanding of the mechanism of drug resistance in ICI therapy in LUAD. However, further investigations are urgently needed to be conducted to determine how this resistance can be overcome.

A tunable metal-polyaniline interface for efficient carbon dioxide electro-reduction to formic acid and methanol in aqueous solution.

It is reported that metals on polyaniline (PANI) prepared by a simple method can exhibit excellent activity in the electro-reduction of CO2 to HCOOH or CH3OH due to tunable properties: N atoms on PANI capture CO2 through a strong Lewis acid-base interaction while Pd atoms, amongst Pd, Pt, and Cu studied, facilitate the fastest proton and electron transfers along PANI to the CO2 trapped sites to give rise to the best HCOOH yield in a highly cooperative manner.

Sulphate-activated growth of bamboo-like carbon nanotubes over copper catalysts.

A sulphate-activated mechanism is proposed to describe the growth of bamboo-like carbon nanotubes (CNTs) over copper catalysts using chemical vapour deposition with helium-diluted ethylene. Sulphate-assisted copper catalysts afford a high-yield growth of bamboo-like CNTs at a mild temperature, 800 °C; however, non-sulphate-assisted copper catalysts, e.g., copper acetate and copper nitrate prepared catalysts, were inert to CNT growth and only gave amorphous carbons (a-C) surrounding copper nanoparticles under the same conditions. Nevertheless, the addition of sulphate ions in the preparation step for the two inert catalysts can activate their abilities for CNT growth with remarkable yields. Furthermore, Raman spectra analysis demonstrates a linear dependence between the concentration of sulphate ions in copper catalysts and the ratio of CNT-a-C in the as-grown carbon soot. The sulphate-activated effect on CNT growth over copper catalysts could be related to a three-way interaction of sulphate ions, copper nanoparticles and support. In situ TEM images of an as-grown CNT irradiated by electron beams without the inlet of carbon sources reveal a new pathway of carbon diffusion through the bulk of copper nanoparticles and an enlarged inner-wall thickness of the on-site CNT. This carbon diffusion model over copper catalysts can provide new insights into the CNT growth mechanism over non-magnetic metal catalysts.

Self-assembly formation of multi-walled carbon nanotubes on gold surfaces.

We report on the observation of self-assembled carbon nanostructures on a standard transmission electron microscopy (TEM) Au substrate formed via thermal chemical vapor deposition. Multi-walled carbon nanotubes (MWNTs) and other carbon nanostructures (CNs), such as carbon nanofibers and carbon nanoparticles (NPs), could be fabricated through structural transformation of metastable carbon layers on the Au surface during 800-850 °C with the thermal decomposition of ethylene. At these temperatures, we found that Au NPs will form immediately through the structural transformation of the Au grid surface in helium atmosphere. The Au NPs work as active centers to trigger the decomposition of ethylene into carbon atoms, which form metastable carbon layers or amorphous carbon nanobugs, and then form CNs via self-assembling. The growth of CNs was characterized by field-emission scanning electron microscopy (SEM), high-resolution TEM and RAMAN spectroscopy. The transformation of amorphous carbon nanobugs by electron beam irradiation is also recorded by in situ monitoring of TEM.