MiRNA155HG polymorphisms influenced the risk of liver cancer among the Han Chinese population.

BACKGROUND: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk. METHODS: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk. CONCLUSIONS: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.

The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo.

In the present study, we tested the anti-pancreatic cancer activity by AT406, a small-molecule antagonist of IAP (inhibitor of apoptosis proteins). In established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells, treatment of AT406 significantly inhibited cell survival and proliferation. Yet, same AT406 treatment was non-cytotoxic to pancreatic epithelial HPDE6c7 cells. AT406 increased caspase-3/-9 activity and provoked apoptosis in the pancreatic cancer cells. Reversely, AT406' cytotoxicity in these cells was largely attenuated with pre-treatment of caspase inhibitors. AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreatic cancer cells. Bcl-2 inhibition (by ABT-737) or shRNA knockdown dramatically sensitized Panc-1 cells to AT406. In vivo, oral administration of AT406 at well-tolerated doses downregulated IAPs (cIAP1/XIAP) and inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) nude mice. Together, our preclinical results suggest that AT406 could be further evaluated as a promising anti-pancreatic cancer agent.

MiR-497 promotes metastasis of colorectal cancer cells through Nrdp1 inhibition.

We have recently shown that Nrdp1 inhibits phosphorylation of ErB3 in colorectal cancer (CRC) cells, to suppress epidermal growth factor receptor (EGFR) signaling-stimulated MMP7 activation for CRC metastasis. In this study, we examined the control of Nrdp1 in CRC cells. We detected significant increases in miR-497 in CRC specimen, compared to paired normal colorectal tissue. Moreover, we detected a strong positive correlation between miR-497 levels and Nrdp1 levels, and a strong inverse correlation between miR-497 levels and MMP7 levels. In vitro, overexpression of miR-497 in human CRC cells significantly decreased Nrdp1 transcripts and protein, and vice versa. Moreover, overexpression of miR-497 in human CRC cells also significantly increased MMP7 transcripts, cellular protein, and secreted protein, resulting in increases in cell invasiveness in a transwell cell migration assay. Furthermore, we found that MiR-497 directly targeted 3'-UTR of Nrdp1 mRNA to inhibit its translation. Together, our data suggest that the regulation of MMP7 by Nrdp1 in CRC cells could be inhibited by miR-497 through suppressing Nrdp1 translation. Our work thus highlights a novel molecular regulatory machinery that regulates metastasis of CRC.

Two mutations on S2 subunit were critical for Vero cell tropism expansion of infectious bronchitis virus HV80.

Infectious bronchitis virus (IBV) restricts cell tropism. Except for the Beaudette strain, other IBVs cannot infect mammalian cell lines. The limited cell tropism of other IBVs has hindered IBV vaccine development and research on the mechanisms of IBV infection. A novel Vero cell-adapted strain, HV80, has been previously reported. In this study, we constructed recombinants expressing the chimeric S glycoprotein, S1 or S2 subunit of strain H120 and demonstrated that mutations on S2 subunit are associated with the strain HV80 Vero cell adaptation. R687P or P687R substitution recombinants were constructed with the genome backbone of strains HV80 or H120. We found that the RRRR690/S motif at the S2' cleavage site is crucial to the Vero cell adaptation of strain HV80. Another six amino acid substitutions in the S2 subunit of the recombinants showed that the Q855H mutation induced syncytium formation. A transient transfection assay demonstrated the S glycoprotein with the PRRR690/S motif at the S2' cleavage site induced low-level cell-cell fusion, while H855Q substitution hindered cell-cell fusion and blocked cleavage event with S20 product. This study provides a basis for the construction of IBV recombinants capable of replicating in Vero cells, thus contributing to the advancement in the development of genetically engineered cell-based IBV vaccines.

MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1.

BACKGROUND: Homoharringtonine (HHT) is a kind of cephalotaxus alkaloid used in traditional Chinese medicine. Although HHT has been successfully used as a therapeutic agent for leukemia, the drug resistance and toxicity are major concerns. MicroRNAs (miRNAs) have been identified to modulate cellular sensitivity to anticancer drugs. We examined the synergistic action between miR-370 and HHT in vitro and in vivo. METHODS: The synergistic action between miR-370 and HHT was examined by flow cytometry. The effect of HHT on miR-370 expression was determined by quantitative RT-PCR (qRT-PCR). The expression of miR-370 and Forkhead box M1 (FoxM1) in 23 patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) and 10 patients with blast-crisis CML (CML-BP) as well as miR-370-targeted FoxM1 was determined by qRT-PCR and western blot analysis. RESULTS: Ectopic expression of miR-370 sensitized the CML K562 cell line to HHT by targeting FoxM1, the major regulator in cell proliferation and apoptosis. miR-370 significantly promoted HHT-mediated cell apoptosis and miR-370 and HHT cooperated in affecting FoxM1 expression. As well, miR-370 was moderately upregulated after HHT treatment in K562 cells. In addition, the expression of miR-370 was significantly reduced in CML patients as compared with healthy controls. Furthermore, the expression of miR-370 was lower in CML-BP than CML-CP patients. CONCLUSIONS: MiR-370 sensitized K562 cells to HHT by inducing apoptosis in part by downregulation of FoxM1 expression. These findings may provide further information for CML treatment with HHT.

Differential analysis revealing APOC1 to be a diagnostic and prognostic marker for liver metastases of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC. AIM: To investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC. METHODS: Data from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions. RESULTS: Based on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05). CONCLUSION: APOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.

Downregulation of LHPP Expression Associated with AFP Acts as a Good Prognostic Factor in Human Hepatocellular Carcinoma.

BACKGROUND: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. METHODS: Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. RESULTS: Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. CONCLUSIONS: LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

Evaluation of radical surgical treatment in the management of 58 locally advanced rectal neuroendocrine neoplasms, one multicenter retrospective study.

BACKGROUND: Locally advanced rectal neuroendocrine neoplasms (NENs) are rare, and the therapeutic effects of surgery in improving the prognosis have been questioned in previous reports. MATERIALS AND METHODS: The research included 58 consecutive patients with locally advanced rectal NENs from three Chinese medical centers between 2000 and 2020. All have received radical surgical treatment. The clinicopathological and survival data were collected. Kaplan-Meier methods and a Cox proportional hazards regression model were used to evaluate the prognosis and identify independent prognostic factors. RESULTS: All patients were followed up for a median period of 36 (2-125) months. Of the 58 patients, 13 (22.4%) had G1 neuroendocrine tumors (NETs), 15 (25.9%) had G2 NETs, 6 (10.3%) had G3 NETs, and the remaining 24 (41.4%) patients had G3 neuroendocrine carcinomas (NECs). The 1-year and 3-year disease-free survival (DFS) rates were 64.5% and 48.8%, respectively. The 1-year and 3-year overall survival (OS) rates were 90.5% and 75.4%, respectively. Univariate analysis demonstrated that tumor differentiation (p = 0.002), gross morphology (p = 0.009), T stage (p = 0.024), and extramural vascular invasion (p = 0.009) were associated with the OS. The subsequent multivariate analysis confirmed that tumor differentiation [hazard ratio (HR) = 6.002, 95% confidence interval (CI): 1.210-29.767, p = 0.028] and gross morphology (HR = 3.438, 95% CI: 1.038-11.382, p = 0.043) were independent prognostic factors affecting the clinical outcomes. CONCLUSIONS: Rectal NENs are a heterogeneous group of diseases. The survival benefits obtained from surgery vary widely based on the tumor clinicopathological features. Patients with G3 NECs and ulcerative mass are at high risks of poor prognosis.

A systematic approach to decode the mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC).

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.

Identification of genes involved in inbreeding depression of reproduction in Langshan chickens.

OBJECTIVE: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. METHODS: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). RESULTS: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. CONCLUSION: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

Development and Validation of a Nomogram and a Comprehensive Prognostic Analysis of an LncRNA-Associated Competitive Endogenous RNA Network Based on Immune-Related Genes for Locally Advanced Rectal Cancer With Neoadjuvant Therapy.

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. In recent years, neoadjuvant chemoradiotherapy (CRT) has been the most comprehensive treatment for locally advanced rectal cancer (LARC). In this study, we explored immune infiltration in rectal cancer (RC) and identified immune-related differentially expressed genes (IRDEGs). Then, we identified response markers in datasets in GEO databases by principal component analysis (PCA). We also utilized three GEO datasets to identify the up- and downregulated response-related genes simultaneously and then identified genes shared between the PCA markers and three GEO datasets. Based on the hub IRDEGs, we identified target mRNAs and constructed a ceRNA network. Based on the ceRNA network, we explored prognostic biomarkers to develop a prognostic model for RC through Cox regression. We utilized the specimen to validate the expression of the two biomarkers. We also utilized LASSO regression to screen hub IRDEGs and built a nomogram to predict the response of LARC patients to CRT. All of the results show that the nomogram and prognostic model offer good prognostic value and that the ceRNA network can effectively highlight the regulatory relationship. hsa-mir-107 and WDFY3-AS2 may be prognostic biomarkers for RC.

[Full-length cDNA sequence analysis of avian leukosis viruses subgroup J isolated from chickens with clinical hemangioma].

OBJECTIVE: To understand the molecular characteristics of subgroup J Avian Leukosis Viruses (ALV-J) isolated from chickens with clinical hemangioma, as well as to get more information for controlling the spread of ALV-J in layer chickens flocks. METHOD: We amplified the full-length viral cDNA sequences of three layers isolates associated with simple hemangioma or coexisting of hemangioma and myeloid leukosis (ML) by PCR. We also obtained some partial sequences of three layer isolates related to hemangioma and one layer isolate from ML case. Then we analyzed and compared the sequences by using DNAstar software. RESULTS: The phylogentic analysis showed the significant differences in the complete sequences between isolates from layer hemangioma cases and from broilers, which were grouped to two branches in the phylogenetic tree. We noted a special 19bp insertion mutation in Primer Binding Site (PBS)-Leader sequences in both JS09GY3 and JS09GY6 isolates from layer chickens with hemangioma and ML, which sequence was same to Rous Associated Virus type 1 (RAV-1), Rous Associated Virus type 2 (RAV-2) and Rous sarcoma virus (strain Schmidt-Ruppin B) (RSV-SRB). In addition, different continuous sequences deletions were found in the U3 regions of NHH and JS09GY5. By motif analysis, we found some distinct motifs including c-Est-1, TCF11 and C/EBP only in the isolates from layers with hemangioma. The five isolates associated with layer hemangioma exhibited intact E element sequences but almost identical substantial deletion was found in all Chinese broiler isolates. An 11bp continuous nucleotide insertion in the E element of JS09GY3 was found. CONCLUSION: Isolates from layer showing hemangioma and broilers exhibited evident difference. We found some special mutation sites in U3, DR1 and the E element showed some potential relationship with the host breeds and the tumor phenotype, which function needs to be investigated in future. The isolates from layer cases with coexisting of hemangioma and ML were the recombinants of ALV-J and other retroviruses.

Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1.

Interleukin-34 (IL-34) is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colony-stimulating factor-1 receptor (CSF-1R). However, information on the function of IL-34 in fish remains limited. In the present study, we identified an IL-34 homolog from mudskippers ( Boleophthalmus pectinirostris). In silico analysis showed that the mudskipper IL-34 (BpIL-34) was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper ( Epinephelus coioides) homolog. BpIL-34 transcripts were constitutively expressed in various tissues, with the highest level of expression found in the brain. Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues. The recombinant mature BpIL-34 peptide (rBpIL-34) was purified and used to produce anti-rBpIL-34 IgG. Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages (MOs/MФs) was N-glycosylated. In vitro, rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs, as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor α ( BpTNF-α) and BpIL-1ß in these cells. Furthermore, the knockdown of mudskipper CSF-1R1 ( BpCSF-1R1), but not mudskipper BpCSF-1R2, significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФ function. In conclusion, our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

MIR17HG polymorphism (rs7318578) is associated with liver cancer risk in the Chinese Han population.

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways.

Low ligation has a lower anastomotic leakage rate after rectal cancer surgery.

BACKGROUND: For laparoscopic rectal cancer surgery, the inferior mesenteric artery (IMA) can be ligated at its origin from the aorta [high ligation (HL)] or distally to the origin of the left colic artery [low ligation (LL)]. Whether different ligation levels are related to different postoperative complications, operation time, and lymph node yield remains controversial. Therefore, we designed this study to determine the effects of different ligation levels in rectal cancer surgery. AIM: To investigate the operative results following HL and LL of the IMA in rectal cancer patients. METHODS: From January 2017 to July 2019, this retrospective cohort study collected information from 462 consecutive rectal cancer patients. According to the ligation level, 235 patients were assigned to the HL group while 227 patients were assigned to the LL group. Data regarding the clinical characteristics, surgical characteristics and complications, pathological outcomes and postoperative recovery were obtained and compared between the two groups. A multivariate logistic regression analysis was performed to evaluate the possible risk factors for anastomotic leakage (AL). RESULTS: Compared to the HL group, the LL group had a significantly lower AL rate, with 6 (2.8%) cases in the LL group and 24 (11.0%) cases in the HL group (P = 0.001). The HL group also had a higher diverting stoma rate (16.5% vs 7.5%, P = 0.003). A multivariate logistic regression analysis was subsequently performed to adjust for the confounding factors and confirmed that HL (OR = 3.599; 95%CI: 1.374-9.425; P = 0.009), tumor located below the peritoneal reflection (OR = 2.751; 95%CI: 0.772-3.985; P = 0.031) and age (≥ 65 years) (OR = 2.494; 95%CI: 1.080-5.760; P = 0.032) were risk factors for AL. There were no differences in terms of patient demographics, pathological outcomes, lymph nodes harvested, blood loss, hospital stay and urinary function (P > 0.05). CONCLUSION: In rectal cancer surgery, LL should be the preferred method, as it has a lower AL and diverting stoma rate.

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and lacks specific diagnostic markers. In this study, we utilized 10 public datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) database to identify a set of significantly differentially expressed genes (DEGs) between tumor and control samples and WGCNA (Weighted Gene Co-Expression Network Analysis) to construct gene co-expression networks incorporating the DEGs from The Cancer Genome Atlas (TCGA) and then identify genes shared between the GEO datasets and key modules. Then, these genes were screened via MCC to identify 20 hub genes. We utilized regression analyses to develop a prognostic model and utilized the random forest method to validate. All hub genes had good diagnostic value for CRC, but only CLCA1 was related to prognosis. Thus, we explored the potential biological value of CLCA1. The results of gene set enrichment analysis (GSEA) and immune infiltration analysis showed that CLCA1 was closely related to tumor metabolism and immune invasion of CRC. These analysis results revealed that CLCA1 may be a candidate diagnostic and prognostic biomarker for CRC.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients.

BACKGROUND: Epidemiologically, in China, locally advanced rectal cancer is a more common form of rectal cancer. Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival (DFS) and pathologic response after surgery. At present, this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers, but the optimal time for surgery after neoadjuvant therapy is still controversial. AIM: To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer. METHODS: A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (≤ 9 wk), and 92 (39.2%) patients were in group B (> 9 wk). DFS and pathologic response were analyzed as the primary endpoints. The secondary endpoints were postoperative complications and sphincter preservation. RESULTS: For the 231 patients included, surgery was performed at ≤ 9 wk in 139 (60.2%) patients and at > 9 wk in 92 (39.8%). The patients' clinical characteristics, surgical results, and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis. The overall pathologic complete response (pCR) rate was 27.2% (n = 25) in the longer time interval group (> 9 wk) and 10.8% (n = 15) in the shorter time interval group (≤ 9 wk, P = 0.001). The postoperative complications did not differ between the groups (group A, 5% vs group B, 5.4%; P = 0.894). Surgical procedures for sphincter preservation were performed in 113 (48.9%) patients, which were not significantly different between the groups (group A, 52.5% vs group B, 43.5%; P = 0.179). The pCR rate was an independent factor affected by time interval (P = 0.009; odds ratio [OR] = 2.668; 95%CI: 1.276-5.578). Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval (> 9 wk) was a significant independent prognostic factor for DFS (P = 0.032; OR = 2.295; 95%CI: 1.074-4.905), but the time interval was not an independent prognostic factor for overall survival (P > 0.05). CONCLUSION: A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer. Neoadjuvant chemoradiotherapy (NCRT) can effectively reduce the postoperative recurrence rate; thus, NCRT with total mesorectal excision (TME) is the most widely accepted standard of care for rectal cancer. The addition of lateral lymph node dissection (LLND) after NCRT remains a controversial topic. AIM: To investigate the surgical outcomes of TME plus LLND, and the possible risk factors for lateral lymph node metastasis after NCRT. METHODS: This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018. In the NCRT group, TME plus LLND was performed in patients with short axis (SA) of the lateral lymph node greater than 5 mm. In the non-NCRT group, TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm. Data regarding patient demographics, clinical workup, surgical procedure, complications, and outcomes were collected. Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients. RESULTS: LLN metastasis was pathologically confirmed in 35 patients (39.3%): 26 (41.3%) in the NCRT group and 9 (34.6%) in the non-NCRT group. The most common site of metastasis was around the obturator nerve (21/35) followed by the internal iliac artery region (12/35). In the NCRT patients, 46% of patients with SA of LLN greater than 7 mm were positive. The postoperative 30-d mortality rate was 0%. Two (2.2%) patients suffered from lateral local recurrence in the 2-year follow up. Multivariate analysis showed that cT4 stage (odds ratio [OR] = 5.124, 95% confidence interval [CI]: 1.419-18.508; P = 0.013), poor differentiation type (OR = 4.014, 95%CI: 1.038-15.520; P = 0.044), and SA ≥ 7 mm (OR = 7.539, 95%CI: 1.487-38.214; P = 0.015) were statistically significant risk factors associated with LLN metastasis. CONCLUSION: NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter, poorer histological differentiation, or advanced T stage. Selective LLND for NCRT patients can have a favorable oncological outcome.

Corrigendum: Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

[This corrects the article DOI: 10.3389/fonc.2020.573295.].