2024-04-20 2024, Volume 13 Issue 4

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  • ORIGINAL ARTICLE
    Yuan Yin , Zhiyan Zou , Jianjun Wang , Xueting Zheng , Mingsong Shi , Jie Ren , Zhaodong Li , Jiwen Luo , Xiaoan Li
    2024, 13(4): 192-203. https://doi.org/10.1002/prm2.12151

    Inflammation affects the progression and therapeutic response of esophageal squamous cell carcinoma (ESCC). The molecular subtypes based on inflammatory response are still under exploitation for clinical application. Expression of inflammation-related hallmark genes was extracted from three ESCC datasets for subtype clustering using the non-negative matrix factorization method. The most stable subtype across datasets was identified using a SubMap analysis. The immune status and molecular characteristics of the stable subtype were explored by comparing with other subtypes, and a classifier was constructed and evaluated using machine learning methods. We identified a subtype of ESCC with a higher inflammatory response score, supported by three datasets, indicating its prevalence. This subtype exhibited a high level of immune infiltration, enriched with CD8+ T cells and various immunosuppressive cells, along with elevated expression of immune checkpoints. It also showed a significant similarity to melanomas responsive to immune checkpoint inhibitor nivolumab, suggesting potential therapeutic benefits. Further analysis revealed that some hub genes in immune pathways likely contribute to the immunosuppressive microenvironment of the subtype and hold prognostic value. We developed an 11-gene classifier for this subtype with an impressive area under the curve (AUC) of 0.9871. Applying it to external data, we identified a group with a similar immunosuppressive environment and potential response to immune checkpoint inhibitors. Generally speaking, the stable subtype we identified will be helpful to guide clinical diagnosis and treatment for ESCC.

  • ORIGINAL ARTICLE
    Peng Xie , Yujie Zhang , Jin Shang , Hanxu Yu , Mingyu Du , Jian Shu , Qiang Wei , Zeyu Zhu , Xia He
    2024, 13(4): 204-213. https://doi.org/10.1002/prm2.12152

    This study was to determine the involvement of long non-coding RNA C7orf13 in nasopharyngeal carcinoma (NPC) and its underlying mechanism. Real-time quantitative PCR results indicated that C7orf13 was overexpressed in NPC and associated with malignant features. C7orf13 knockdown significantly suppressed the proliferation, migration and invasion of NPC cells. Furthermore, we found that C7orf13 sequestered miR-449c and miR-28-5p in NPC cells by dual-luciferase reporter assays and RNA immunoprecipitation analysis. Sequent experiments showed that C7orf13 has a positive relationship with formin-like 2 (FMNL2) in NPC tissues. Moreover, C7orf13 knockdown weakened FMNL2-mediated cell invasion and migration. Finally, functional experiments revealed that the positive effect of C7orf13 on cell migration and invasion was mediated by the miR-449c/miR-28-5p-FMNL2 axis. Generally, our study identifies the biological role of long non-coding RNA C7orf13 in the malignant process of NPC, which may pave a new way for the diagnosis and treatment of NPC.

  • ORIGINAL ARTICLE
    Liang Gui , Jian Wang
    2024, 13(4): 214-220. https://doi.org/10.1002/prm2.12143

    Cancers of the digestive tract are a series of diseases that seriously affects the health and life quality of the population worldwide, and the etiology is closely related to various daily habits. Drinking water is a daily human activity, but the intrinsic connection between water intake and gastrointestinal (GI) cancers is still unclear. We used the two-sample mendelian randomization (TSMR) method to explore the potential causal relationship between water consumption and GI cancers. We obtained the integrated GWAS data of water intake (ukb-b-14 898), as well as the GWAS results of oral cavity cancer (ieu-b-4961), esophageal cancer (ebi-a-GCST90018841), gastric cancer (ebi-a-GCST90018849), liver cancer (ieu-b-4953), hepatic bile duct cancer (ebi-a-GCST90018803), pancreatic cancer (ebi-a-GCST90018893) and colorectal cancer (ebi-a-GCST90018588) through the online database “IEU OPEN GWAS PROJECT”. Using inverse variance weighting (IVW) method, weighted median method, MR Egger regression method, simple model method, and weighted model method to jointly study the causal relationship between water intake and GI cancers. Mendelian randomization analysis showed a negative correlation between water consumption and esophageal cancer (weighted media, OR = 0.215, p = .021; MR Egger, OR = 0.033, p = .040; weighted mode, OR = 0.162, p = .045), a positively association with pancreatic cancer (IVW, OR = 2.663, p = .033). There is a potential positive correlation between water intake and gastric cancer as well as colorectal cancer, but not statistically significant. The associations between water intake and oral cavity cancer, liver cancer and hepatic bile duct cancer remain uncertain. Therefore, Increased amount of drinking water may help to prevent the incidence of esophageal cancer, but might promote the development of pancreatic cancer.

  • ORIGINAL ARTICLE
    Lili Feng , Cenzhu Wang , Jiawen Chen , Chenyue Tao , Liuliu Zhang , Luojing Zhou
    2024, 13(4): 221-231. https://doi.org/10.1002/prm2.12146

    Lung cancer is one of the most-common malignant tumors while lung adenocarcinoma (LUAD) serves as the major subtype of lung cancer. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an important choice in LUAD targeted therapies. However, EGFR-TKI acquired resistance always happens, urging for further investigating and overcoming. We acquired the scRNA-seq data of EGFR-TKI acquired resistance in LUAD from GSE149383 and PRJNA591860 databases. We identified the typical tendency during EGFR-TKI acquired resistance progression in LUAD. Furthermore, we investigate the potential expression profiles, upstream transcription factors, and interacting drugs with EGFR-TKI in LUAD, participating in EGFR-TKI acquired resistance. According to scRNA-seq databases, the typical tendency was identified as “decrease early and raise later” during EGFR-TKI acquired resistance progression in LUAD from Day 0 to Day 11. Seven important pairs of upstream transcription factors and target genes were explored during EGFR-TKI acquired resistance in LUAD, including TFDP1-RPA3, TFDP1-EIF2S1, TFDP1-COTL1, TFDP1-CBX1, MYBL2-STMN1, EZH2-CYCS, and BRCA1-STMN1. Several potential interacting drugs with EGFR-TKI were screened in LUAD, especially TANDUTINIB. We identified the typical tendency of “decrease early and raise later” during EGFR-TKI acquired resistance progression in LUAD while we recognized transcription factor-target gene pairs and interacting drugs with EGFR-TKI during EGFR-TKI acquired resistance, which could provide a novel insight for clinical treatments.

  • ORIGINAL ARTICLE
    Yun Ning , Liuliu Zhang , Xiaoxu Zhi , Yun Zhao , Ying Fang , Bing Wu , Zhujie Xu , Lixin Huang , Yi Pei
    2024, 13(4): 232-241. https://doi.org/10.1002/prm2.12132

    Background: As one of the common adverse reactions after chemotherapy in breast cancer patients, chemotherapy-induced nausea and vomiting (CINV) seriously affects the quality of life of breast cancer patients.

    Objective: To explore the application effect of nurse-led CINV management scheme based on risk assessment in breast cancer patients.

    Methods: The researchers selected 90 breast cancer patients who received chemotherapy at Jiangsu Cancer Hospital from June 1, 2022, to June 1, 2023. The patients were divided into control group and intervention group. The control group implemented the routine nursing mode, and the intervention group implemented the nurse-led intervention program based on risk assessment. On this basis, the intervention group applied the symptom management theory to the construction of intervention strategy to compare the CINV situation, quality of life, and psychological distress level between the two groups.

    Results: The frequency of vomiting and the degree of nausea in the delayed stage were lower in the intervention group than in the control group, and the difference was statistically significant (p<.05). The life function index of nausea and vomiting in acute stage and delayed stage was higher in the intervention group than in the control group, and the differences were statistically significant (p<.05). The psychological pain scores of the two groups in the acute stage and the delayed stage were lower in the intervention group than in the control group, and the differences were statistically significant (p<.05).

    Conclusion: Nurse-led CINV management scheme based on risk assessment can effectively reduce the frequency of vomiting, reduce the degree of nausea, improve the quality of life, and alleviate psychological pain in breast cancer patients.