M6A “Writer” Gene METTL14: A Favorable Prognostic Biomarker and Correlated With Immune Infiltrates in Rectal Cancer

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A “writer” gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer.

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CXCL2 as a Prognostic Marker in Breast Cancer is Associated with Immune Infiltration and Regulated by miR-215

10.21203/rs.3.rs-41001/v1 ◽

2020 ◽

Author(s):

Jia-Xiang An ◽

Ying-Ying Chen ◽

Zhao-Sheng Ma ◽

Wen-Jie Yu ◽

Jin-Xi Hu ◽

...

Keyword(s):

Breast Cancer ◽

Survival Time ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Clinical Prognosis ◽

Immune Infiltration ◽

Kaplan Meier ◽

The Impact ◽

Kaplan Meier Plotter ◽

Low Expression

Abstract Background: CXCL2 is a part of chemokine superfamily, which encodes secretory proteins involved in immune regulation and inflammation. The correlation between CXCL2 and prognosis of different cancers, tumor infiltrating lymphocytes are not clear. Methods: We analyzed the expression of CXCL2 and its effect on clinical prognosis through Oncomine database, Tumor Immune Estimation Resource (TIMER) website, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA were used to analyze the correlation between CXCL2 and the gene marker of immune infiltration. StarBase was used to predict the miRNA that may regulate CXCL2. The relationship between miR-532-5p and CXCL2 was detected by qRT-PCR. Kaplan-Meier plotter was used to evaluate the impact of miR-532-5p on clinical prognosis. Results: PrognoScan, Kaplan-Meier plotter and GEPIA database analysis showed that low expression of CXCL2 was associated with poor disease-specific survival time (DSS), relapse-free survival time (RFS) and overall disease survival (OS) in breast cancer patients. In addition, low expression of CXCL2 was associated with poor OS and RFS in patients with lymph node positive breast cancer. CXCL2 expression was positively correlated with the infiltration of B cells, CD4+T and CD8+T cells, neutrophils and dendritic cells (DCs) in BRCA, mainly in Luminal breast cancer. MiR-532-5p can directly regulate CXCL2 expression. High miR-532-5p expression is significantly correlated with HER2 negative, grade 2 and 3 and poor OS in patients with HER+ER- breast cancer. Conclusion: CXCL2 is closely related to the prognosis and immune infiltration level of breast cancer patients, it can be regulated by miR-532-5p.

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MCUR1 is a prognostic biomarker for ovarian cancer patients

Cancer Biomarkers ◽

10.3233/cbm-210166 ◽

2021 ◽

pp. 1-6

Author(s):

Liming Fan ◽

Hualiang Yang ◽

Bo Zhang ◽

Hong Ding

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Immune Cell ◽

Prognostic Biomarker ◽

Cancer Prognosis ◽

High Expression Group ◽

Potential Biomarker ◽

Patient Specimen ◽

Ovarian Cancer Prognosis ◽

Low Expression

PURPOSE: To propose MCUR1 gene as a potential biomarker for ovarian cancer prognosis. METHODS: The ovarian cancer patient specimen from TCGA database were analyzed using survival analysis. The immune cell infiltration ratio and checkpoints had also been investigated for different expression group of MCUR1. The function of MCUR1 as a ovarian cancer prognosis biomarker was verified in clinic. RESULTS: The low expression of MCUR1 was associated with the poor prognosis of ovarian cancer patients. The expressions of majority of immune cells and 6 checkpoints in low expression group of MCUR1 were significantly lower than that in high expression group of MCUR1 (P< 0.05). The MCUR1 could be utilized as a prognostic biomarker for ovarian cancer patients in clinic. CONCLUSION: This study has proposed a potential prognostic biomarker for ovarian cancer patients, which offers a beneficial reference for future ovarian cancer administration.

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Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

BMC Cancer ◽

10.1186/s12885-021-08260-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hanna Abrahamsson ◽

Sebastian Meltzer ◽

Vidar Nyløkken Hagen ◽

Christin Johansen ◽

Paula A. Bousquet ◽

...

Keyword(s):

Rectal Cancer ◽

Vitamin D ◽

Cancer Patients ◽

Systemic Inflammation ◽

Elevated Serum ◽

Metastatic Progression ◽

Vitamin D Status ◽

Cancer Specific Survival ◽

Link Type ◽

The Impact

Abstract Background We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients. Methods Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013–2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival. Results In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex. Conclusion This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women. Trial registration ClinicalTrials.govNCT01816607; registration date: 22 March 2013.

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Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples

10.21203/rs.3.rs-36422/v1 ◽

2020 ◽

Author(s):

Qiang Liu ◽

Yihang Qi ◽

Jie Zhai ◽

Xiangyi Kong ◽

Xiangyu Wang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Immune Cell ◽

Immune Checkpoints ◽

Cell Populations ◽

Potential Biomarker ◽

The Impact

Abstract Background Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, a large number of cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, is a protein Coding gene served as alternative inhibitory receptors to be targeted in the clinic. The impact of LAG3 on immune cell populations and co-regulation of immune response in breast cancer remained largely unknown. Methods To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from a total of 2994 breast cancer patients. Results We observed that LAG3 was closely correlated with major molecular and clinical characteristics, and was more likely to be enriched in higher malignant subtype, suggesting LAG3 was a potential biomarker of triple-negative breast cancer. Furthermore, we estimated the landscape of relationship between LAG3 and ten types of cell populations in breast cancer. Gene ontology analysis revealed LAG3 were strongly correlated with immune response and inflammatory activities. We investigated the correlation pattern between LAG3 and immune modulators in pan-cancer, especially the synergistic role of LAG3 with other immune checkpoints members in breast cancer. Conclusions LAG3 expression was closely related to malignancy of breast cancer and might serve as a potential biomarker; LAG3 might plays an important role in regulating tumor immune microenvironment, not only T cells, but also other immune cells. More importantly, LAG3 might synergize with CTLA4, PD1/ PDL1 and other immune checkpoints, thereby lending more evidences to combination cancer immunotherapy by targeting LAG3, PD1/PDL1, and CTLA4 together.

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Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01796-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Liyuan Song ◽

Xianhui Wang ◽

Wang Cheng ◽

Yi Wu ◽

Min Liu ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Markers ◽

Cancer Patients ◽

Targeted Therapies ◽

Poor Prognosis ◽

Immune Cell ◽

Clinicopathological Parameters ◽

Cancer Specific Survival ◽

Lung Cancer Patients ◽

Favorable Prognosis

Abstract Background In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear. Methods CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan–Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein–protein interaction and gene–gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively. Results CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients. Conclusions CTSF might play an anti-tumor effect via regulating immune response of NSCLC.

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Low expression of RGL4 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients

International Immunopharmacology ◽

10.1016/j.intimp.2020.106454 ◽

2020 ◽

Vol 83 ◽

pp. 106454 ◽

Cited By ~ 1

Author(s):

Yidan Sun ◽

Ying Zhang ◽

Shiqi Ren ◽

Xiaojiang Li ◽

Peiying Yang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Immune Infiltration ◽

Low Expression

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Association of mismatch repair status with survival and response to neoadjuvant chemo(radio)therapy in rectal cancer

npj Precision Oncology ◽

10.1038/s41698-020-00132-5 ◽

2020 ◽

Vol 4 (1) ◽

Cited By ~ 1

Author(s):

Shu-Biao Ye ◽

Yi-Kan Cheng ◽

Lin Zhang ◽

Yi-Feng Zou ◽

Ping Chen ◽

...

Keyword(s):

Rectal Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Stage Iii ◽

Neoadjuvant Radiotherapy ◽

Radio Therapy ◽

Colorectal Cancer Patients ◽

The Impact

Abstract Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. However, the impact of MMR status on response to neoadjuvant radiotherapy in rectal cancer is not well understood. Here we report that dMMR was associated with improved disease-free survival (DFS) (P = 0.034) in patients receiving neoadjuvant chemotherapy (NCT). Patients with dMMR tumors who received neoadjuvant chemoradiotherapy (NCRT) achieved significantly worse DFS (P = 0.026) than those treated with NCT. Conversely, NCRT improved DFS (P = 0.043) in patients with pMMR tumors, especially for stage III disease with improved DFS (P = 0.02). The presence of dMMR was associated with better prognosis in rectal cancer patients treated with NCT. NCT benefited patients with dMMR tumors; while NCRT benefited patients with stage III disease and pMMR tumors. Patients stratified by MMR status may provide a more tailored approach to rectal cancer neoadjuvant therapy.

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HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14616 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14616-e14616

Author(s):

Francesco Sclafani ◽

Amitesh Chandra Roy ◽

Ian Chau ◽

Andrew Wotherspoon ◽

Clare Peckitt ◽

...

Keyword(s):

Rectal Cancer ◽

High Risk ◽

Cancer Patients ◽

Therapeutic Target ◽

Predictive Biomarker ◽

Secondary Endpoints ◽

Her 2 ◽

Low Prevalence ◽

The Impact

e14616 Background: HER-2 is a well established therapeutic target in breast and gastric cancer. The role of HER-2 in rectal cancer is unclear, as conflicting data on prevalence of HER-2 expression have been reported. Preclinical data indicate a potential role of HER-2 in mediating resistance of rectal cancer to chemoradiotherapy and cetuximab. This analysis evaluates the prevalence of HER-2 and its impact on the outcome of high risk rectal cancer patients treated with neoadjuvant CAPOX and CRT ± cetuximab in EXPERT-C. Methods: Eligible patients with available tumour tissue for HER-2 analysis were included. HER-2 expression was determined by immunohistochemistry (IHC) in biopsy and/or surgical specimens (score 0 to 3+). Tumours with equivocal IHC result (2+) were tested for HER-2 amplification by B-DISH. Tumours with IHC 3+ or B-DISH ratio ≥2.0 were classified as HER-2 positive. The impact of HER-2 on primary (CR) and secondary endpoints (RR, PFS, OS) of the study was analyzed. Results: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3/104 (2.9%) and 3/114 (2.6%) were HER-2 positive, respectively. In 77 patients with paired specimens, concordance for HER-2 status was found in 74 (96%). Overall 141 patients were assessable for HER-2; 6/141 (4.3%) had a HER-2 positive tumour in at least 1 specimen. The median follow-up was 58.7 months. HER-2 expression or amplification was not associated with a difference in outcome for any of the study endpoints, including in the subset of 90 KRAS/BRAF wild type patients treated ± cetuximab. In an exploratory analysis, 44 IHC 0/1+ random specimens were tested by B-DISH and HER-2 amplification was found in 3/38 (7.9%, insufficient material in 6 cases). Conclusions: Based on the low prevalence of expression (according to the classical criteria for defining HER-2 positivity) as recorded in EXPERT-C, HER-2 does not appear to represent a useful therapeutic target for high risk rectal cancer. We did not confirm the role of HER-2 as prognostic factor or potential predictive biomarker for cetuximab-based treatment.

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U.S. trends and racial/ethnic disparities in opioid access among patients with poor prognosis cancer at the end of life (EOL).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.7005 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 7005-7005

Author(s):

Andrea Catherine Enzinger ◽

Kaushik Ghosh ◽

Nancy Lynn Keating ◽

David M Cutler ◽

Mary Beth Landrum ◽

...

Keyword(s):

End Of Life ◽

Cancer Patients ◽

Poor Prognosis ◽

Ethnic Disparities ◽

Opioid Prescription ◽

Ed Visits ◽

The Impact ◽

To Receive ◽

Racial Ethnic ◽

Patients With Poor Prognosis

7005 Background: Heightened US opioid regulations may limit advanced cancer patients’ access to effective pain management, particularly for racial/ethnic minority and other vulnerable populations. We examined trends in opioid access, disparities in access, and pain-related emergency department (ED) visits among cancer patients near end of life (EOL). Methods: Using a 20% random sample of Medicare FFS beneficiaries, we identified 243,124 patients with poor prognosis cancers who died between 2007-2016. We examined trends in outpatient opioid prescription fills and pain-related ED visits near EOL (30 days prior to death or hospice enrollment), for the overall cohort and by race (white, black, other). Per-capita opioid supply by state was obtained from the federal Drug Enforcement Agency ARCOS database. Geographic fixed-effects models examined predictors of opioid use near EOL, opioid dose in morphine milligram equivalents (MMEs), and pain-related ED visits, adjusted for patient demographic and clinical characteristics, state, opioid supply, and year. Results: From 2007-2016 the proportion of patients with poor prognosis cancers filling an opioid prescription near EOL fell from 41.7% to 35.7%, with greater decrements among blacks (39.3% to 29.8%) than whites (42.2% to 36.5%) and other races (38.2% to 32.4%). The proportion of patients receiving long-acting opioids near EOL fell from 17% to 12% overall (15% to 9% among blacks). Among patients receiving EOL opioids, the median daily dose fell from 40MMEs (IQR 16.5-98.0) to 30MMEs (IQR 15.0–78.8). In adjusted analyses, blacks were less likely than whites to receive EOL opioids (AOR 0.85; 95% CI, 0.80 to 0.91) and on average received 10MMEs less per day (b -9.9; 95% CI -15.7 to -4.2). Patients of other race were also less likely to receive EOL opioids (AOR 0.92; 95% CI, 0.85-0.95), although their dose did not differ significantly from whites. Rates of pain-related ED visits near EOL increased from 13.2% to 18.8% over the study period. In adjusted analyses, blacks were more likely than whites to have pain-related ED visits (AOR 1.29, 95% CI, 1.16-1.37) near death, as were those of other races (AOR 1.30; 95% CI, 1.17-1.37). Conclusions: While lawmakers have sought to mitigate the impact of opioid regulations upon cancer patients, access to EOL opioids have decreased substantially over time with concomitant increases in pain-related ED visits. There are significant racial/ethnic disparities in opioid access, with blacks receiving fewer opioids at lower doses and having more ED-based care for pain near EOL.

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