Loss of LIMCH1 predicts poor prognosis in patients with surgically resected Lung Adenocarcinoma: A study based on Immunohistochemical Analysis and Bioinformatics

Abstract

Background: LIMCH1, a novel actin-binding protein, is reported to correlate with tumorigenesis in multiple cancer types, but its clinical prognostic value in lung adenocarcinoma (LUAD) patients remains unclear. Methods: A total of 196 patients with LUAD who underwent R0 resection were included for analysis. We integrated immunohistochemistry (IHC) and data mining analyses to determine LIMCH1 expression in tumor specimens; the chi-square test was used to explore the correlation between clinicopathologic factors and LIMCH1 expression in LUAD; Kaplan-Meier curves and the Cox proportional hazards model were used to investigate the clinical prognostic role of LIMCH1 expression in patients with LUAD; and DAVID enrichment and gene set enrichment analysis (GSEA) were used to determine the underlying molecular mechanism. Results: LIMCH1 protein and mRNA expressions were significantly decreased in LUAD tissues. LIMCH1 mRNA expression was a potential diagnostic indicator in the TCGA cohort, and was associated with poor prognosis. IHC results in our LUAD cohort demonstrated that the LIMCH1 expression level was significantly associated with pleural invasion, tumor length, tumor differentiation grade, and clinical tumor stage. Patients with higher LIMCH1 expression had longer overall survival times. Cox multivariate survival analysis showed that LIMCH1 expression independently predicted the outcome. GO and KEGG clustering analyses showed that LIMCH1-related genes may be involved in 'cell adhesion', 'signal transduction', and several cancer-related pathways. GSEA showed 8 enriched hallmarks in the low LIMCH1 expression group, including mTOR signaling, MYC signaling, DNA repair, and G2M checkpoint. Conclusions: Our findings suggest that LIMCH1 may serve as a promising biomarker to predict LUAD prognosis.

LIMCH1 as a New Potential Metastasis Predictor in Breast Cancer

“…It is also shown that LIMCH1 protein is a transcription factor that promotes the expression of p53 LIMCH1 protein is regarded as a typical tumor suppressor due to its functions such as suppressing cells migration and promoting expression of p53. Actually, in lung (Zhang et al, 2019;Cao et al, 2021) and renal (https://www.proteinatlas.org/ENSG00000064042-LIMCH1/pathology/renal+cancer) carcinoma, it has been shown that LIMCH1 protein expression can be a favorable prognostic factor. However, the clinical and prognostic value of LIMCH1 protein expression in breast cancer is not enough explored.…”

“…LIMCH1 protein regulates the activity of non-muscle myosin type 2A (NMIIA). It also promotes retrograde actin flow in lamellipodia and increases the strength of focal adhesion, preventing cell migration and increasing cell adhesion (Lin et al, 2017) described as a favorable prognostic factor in lung (Zhang et al, 2019;Cao et al, 2021) and renal cancers (https:// www.proteinatlas.org/ENSG00000064042-LIMCH1/ pathology/renal+cancer). However, its role in breast cancer remains unexplored.…”

Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study

“…LIMCH1 has been identified as a key regulator of actin-cytoskeleton remodelling, involved in cell migration [ 22 ]. Due to its role in cell migration and adhesion, LIMCH1 has been associated with worse prognosis in multiple forms of cancer [ 33 ]. While LIMCH1 has not been directly associated with nerve function, actin-cytoskeletal frameworks are critical in neuronal development, and axonal growth and actin-binding LIM domain proteins are important in axonal regeneration [ 34 ].…”

The role of Limch1 alternative splicing in skeletal muscle function

“…Silencing of LIMCH1 led to disrupted focal adhesions and a subsequent increase in cell migration 21 . Several reports have linked LIMCH1 depletion to cancer progression suggesting reduced LIMCH1 levels may serve as a biomarker for tumor growth and/or metastasis in lung, breast and cervical cancers [22][23][24][25][26][27] . Beyond the role of LIMCH1 in focal adhesion formation and cell migration in vitro, nothing is known about its role in tissue-specific development or physiology.…”

“…25 and 400 ms, respectively, were used to assess contractile properties of the muscle with current passing through two platinum electrodes (PanLab LE 12406, Harvard Apparatus).Kinetics, force-frequency, fatigue, and recovery from fatigue protocols were collected and analyzed in LabChart 8 (ADInstruements) with the Peak Analysis module. Forcefrequency was tested by stimulating the muscle at 1 Hz, 5 Hz, 10 Hz, 20 Hz, 40 Hz, 60 Hz, 80 Hz, 120 Hz, 150 Hz and 200 Hz with one minute intervals between each frequency tested.…”