Analysis of Spatial Transcriptomics of MARCH5 and Its Potential Role on Cell Proliferation in Breast Cancer

Breast cancer (BC) represents the most frequently occurring cancer and is the leading cause of cancer-related deaths among female patients worldwide. MARCH5 plays a key role in the maintenance of mitochondrial fitness, dynamics and quality control through its E3 ligase activity. However, the spatial expression of MARCH5 in human BC and its possible mechanisms accounting for cancer progression have yet to be determined. The diagnostic efficacy and prognostic value were confirmed using RNA-seq data source from TCGA samples. The co-expression genes of MARCH5 and Gene Set Enrichment Analysis were analyzed on Linckedomics server to identify key pathway. The associations between MARCH5 and biomarkers relevant to cancer proliferation and cell cycle were determined by Pearson correlation method. The quantitative gene expression with high-resolution tissue imaging was determined using spatial transcriptomics approach. BC tissues showed higher MARCH5 expression than normal tissues. The specificity over various cutoff was above 0.75. High MARCH5 expression was found to be associated with decreased overall survival time. The generalization value was observed in other cancers such as lung adenocarcinoma, pancreatic ductal adenocarcinoma, and renal clear cell carcinoma. DNA replication was identified as one key pathway that is activated by MARCH5 and its co-expression genes. MARCH5 expression in BC presented positive correlation with cell cycle biomarkers, including Ki-67, PCNA, MCM2, CDK4, CDK2, and CDK1. Spatial transcriptomic analysis showed that high levels of MARCH5 was concurrently expressed with MCM2 in human BC tumor. In conclusion, spatial transcriptomics corroborates high MARCH5 expression concurrently with proliferation biomarker in human BC. High MARCH5 can serve as a clinical biomarker for BC with good diagnostic efficacy and predict unfavorable outcome. The involvement of MARCH5 in activating cell cycle plays a factor in BC progression.

關鍵字

Breast cancer ； MARCH5 ； Spatial transcriptomics ； Diagnosis ； Prognosis ； Proliferation ； Cell cycle

並列摘要

乳癌是最常見的癌症，也是全球女性患者癌症相關死亡的主因。MARCH5通過其E3連接酶活性在維持粒線體適應性、動態和質量控制方面發揮關鍵作用。然而，尚未確定MARCH5在人類乳癌中的空間表達及其可能導致癌症進展的機制。使用來自TCGA樣本的RNA-seq數據源確認了診斷功效和預後價值。在Linkedomics伺服器上分析MARCH5和基因集富集分析的共表達基因，以確定關鍵途徑。通過Pearson相關係數分析確定MARCH5與癌症增殖和細胞週期相關的生物標誌物之間的關聯。使用空間轉錄體學方法確定具有高分辨率組織成像的定量基因表達。乳癌組織顯示出比正常組織更高的MARCH5表達。各種截止值的特異性高於0.75。發現高MARCH5表達與降低的總生存時間有關。在肺腺癌、胰腺導管腺癌和腎透明細胞癌等其他癌症中觀察到了泛化價值。DNA複製被確定為由MARCH5及其共表達基因激活的關鍵途徑之一。乳癌中的MARCH5表達與細胞週期生物標誌物呈正相關，包括Ki-67、PCNA、MCM2、CDK4、CDK2和CDK1。空間轉錄體學分析表明，高量MARCH5與MCM2在人類乳癌腫瘤中同時表達。總之，空間轉錄體學證實了人類乳癌中的高MARCH5表達與增殖生物標誌物同時存在。高表達MARCH5可作為乳癌的臨床生物標誌物，具有良好的診斷效果並預測不良結果。MARCH5參與激活細胞週期是乳癌進展的因素之一。

並列關鍵字

乳癌； MARCH5 ；空間轉錄體學；診斷；預後；增生；細胞週期

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