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Abstract：
UNASSIGNED: The tumor microenvironment (TME) plays an important role in tumor progression and immunotherapy responses in non-small cell lung cancer (NSCLC). The programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) checkpoint is a central mediator of immunosuppression in the TME. However, there is still a need to identify additional biomarkers that could reflect the difference in TME and PD-L1 expression in NSCLC patients. To this end, we focused on the expression of G-protein-coupled receptor family C group 5 type A (GPRC5A) in NSCLC. GPRC5A, is a retinoic acid-inducible gene that plays multiple roles in NSCLC. However, little is known about the role of GPRC5A in regulating the TME and PD-L1. Our objective was to describe the critical role of GPRC5A expression in NSCLC in the setting of immune cell infiltration.
UNASSIGNED: We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated GPRC5A as a predictive biomarker by using public databases to reveal the relationship between GPRC5A expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC).
UNASSIGNED: Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low GPRC5A expression and increased infiltration of CD8+ T cells, activated CD4+ T cells, and M1 macrophages within the TME. Furthermore, low GPRC5A expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression.
UNASSIGNED: Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of GPRC5A is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of GPRC5A is associated with immunotherapy, but further validation is still required.
UNASSIGNED: We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated GPRC5A as a predictive biomarker by using public databases to reveal the relationship between GPRC5A expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC).
UNASSIGNED: Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low GPRC5A expression and increased infiltration of CD8+ T cells, activated CD4+ T cells, and M1 macrophages within the TME. Furthermore, low GPRC5A expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression.
UNASSIGNED: Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of GPRC5A is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of GPRC5A is associated with immunotherapy, but further validation is still required.
摘要：
■肿瘤微环境（TME）在非小细胞肺癌（NSCLC）的肿瘤进展和免疫治疗反应中起重要作用。程序性细胞死亡1(PD-1)/程序性细胞死亡-配体1(PD-L1)检查点是TME中免疫抑制的中心介质。然而,目前仍需要鉴定能够反映NSCLC患者中TME和PD-L1表达差异的其他生物标志物.为此,我们关注G蛋白偶联受体C家族5组A型(GPRC5A)在非小细胞肺癌中的表达。GPRC5A,是一种视黄酸诱导基因，在非小细胞肺癌中发挥多种作用。然而,关于GPRC5A在调节TME和PD-L1中的作用知之甚少。我们的目的是描述GPRC5A在NSCLC中的表达在免疫细胞浸润中的关键作用。
■我们在复旦大学上海肿瘤防治中心(FUSCC)队列中确定GPRC5A表达与NSCLC患者临床病理特征之间的关系。此外，我们通过使用公共数据库验证GPRC5A作为预测生物标志物,以揭示GPRC5A表达与免疫细胞浸润之间的关系.为了将GPRC5A的表达与NSCLC样本中PD-L1的空间分布相关联，我们进行了多重免疫组织化学（mIHC）。
■低GPRC5A表达与早期病理阶段(pStage)相关。免疫细胞浸润分析表明，GPRC5A低表达与CD8+T细胞浸润增加之间存在关系，激活的CD4+T细胞，和TME内的M1巨噬细胞。此外，GPRC5A低表达与NSCLC中免疫表型评分(IPS)升高相关.此外,mIHC分析显示GPRC5A低表达与肿瘤PD-L1表达的空间分布之间存在相关性。
■我们的研究揭示了GPRC5A的低表达与NSCLC早期pStage之间的关系。此外，我们观察到GPRC5A的低表达与免疫细胞浸润增加有关，较高的IPS，PD-L1阳性肿瘤细胞的空间分布。因此,我们推测GPRC5A的低表达与免疫治疗有关，但仍需要进一步验证。
■我们在复旦大学上海肿瘤防治中心(FUSCC)队列中确定GPRC5A表达与NSCLC患者临床病理特征之间的关系。此外，我们通过使用公共数据库验证GPRC5A作为预测生物标志物,以揭示GPRC5A表达与免疫细胞浸润之间的关系.为了将GPRC5A的表达与NSCLC样本中PD-L1的空间分布相关联，我们进行了多重免疫组织化学（mIHC）。
■低GPRC5A表达与早期病理阶段(pStage)相关。免疫细胞浸润分析表明，GPRC5A低表达与CD8+T细胞浸润增加之间存在关系，激活的CD4+T细胞，和TME内的M1巨噬细胞。此外，GPRC5A低表达与NSCLC中免疫表型评分(IPS)升高相关.此外,mIHC分析显示GPRC5A低表达与肿瘤PD-L1表达的空间分布之间存在相关性。
■我们的研究揭示了GPRC5A的低表达与NSCLC早期pStage之间的关系。此外，我们观察到GPRC5A的低表达与免疫细胞浸润增加有关，较高的IPS，PD-L1阳性肿瘤细胞的空间分布。因此,我们推测GPRC5A的低表达与免疫治疗有关，但仍需要进一步验证。
