免疫浸润论文：生信论文36、37引文写作

生信论文的套路

1. ONCOMINE从全景、亚型两个维度做表达差异分析；
2. 临床标本从蛋白水平确认（或HPA数据库），很重要；
3. Kaplan-Meier Plotter从临床意义的角度阐明其重要性；
4. cBio-portal数据库做基因组学的分析（机制一）；
5. STRING互作和GO/KEGG分析探讨可能的信号通路（机制二）；
6. TISIDB/TIMER分析肿瘤免疫特征（机制三）。

好的引文是一篇论文成功的一半。

引文的基本内容：介绍背景（一段或两段）、提出问题（一段），解决问题（一段或2段）。一般引文介绍3~5段。

1. 疾病或基因的背景介绍；
2. 前人研究的成果、现实情况，存在的问题；
3. 阐明研究原因或意义。介绍研究的性质、范畴及其重要性，突出研究目的和待解决的科学问题；
4. 研究方法，新发现和意义。

写作举例--生信论文36--胃肠癌。

第一段，介绍胃肠癌的背景。先介绍胃肠癌的流行病学和预后，引出免疫治疗和科学问题；接着，用 in addition再次提升研究的重要性，最后总结出研究的紧迫性。

Gastrointestinal (GI) cancers are the most common malignancy among both men and women worldwide, and metastasis is an important biological feature that leads to a poor prognosis (1). Immune-related mechanisms play an important role in GI cancer, and immunotherapeutic strategies are considered a promising direction for the treatment of GI cancers (2). Immunotherapy, such as cytotoxic T lymphocyte associated antigen 4 (CTLA4), programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, showed promising antitumor effects in malignant melanoma and non-small-cell lung carcinoma (NSCLC) (3, 4). However, current immunotherapies, such as anti-CTLA4 (5, 6), showed poor clinical efficacy in metastatic colorectal and gastric cancers, anti-PD-1 and anti-PD-L1 showed a partial response in advanced colorectal and gastric cancers (7–9). In addition, an increasing number of studies have found that the tumor-infiltrating lymphocytes, such as tumorassociated macrophages (TAMs) and tumor-infiltrating neutrophils (TINs), affect the prognosis and efficacy of chemotherapy and immunotherapy (10, 11). Therefore, there is an urgent need for the elucidation of the immunophenotypes of tumor-immune interactions and identification of novel immune-related therapeutic targets in colorectal and gastric cancers.

第二段介绍LAYN基因的背景，包括发现历史（不重要），表达谱（重要）和功能（最重要），最终引出该基因与肿瘤的相关性（蓝色），并用一系列前人研究来论证。

Layilin (LAYN), which was first reported in 1998, is a protein encoding-gene located on chromosome 11 (12). Layilin, a 55-kDa transmembrane protein with homology to C-type lectin, is expressed in many cell types and organs. Moreover, LAYN proteins can act as a surface receptor for hyaluronan (HA). Thus, LAYN plays an important role in cell adhesion, motility, regulation of cell spreading and migration (13, 14). Previous studies (15) indicate that LAYN is involved in the tumor necrosis factor-α (TNF-α) induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells as well as plays a critical role in HA35-induced intestinal epithelial tight junctions in inflammatory bowel disease (16). LAYN was first shown to be associated with cancer in a report demonstrating that low levels of LAYN protein can reduce cell invasion and lymph node metastasis A549 lung cancer cells (17). These findings suggest the LAYN plays an important role in cancer progression, invasion and metastasis.

第三段，介绍两者关系，提出问题。作者通过前人研究阐释LAYN通过免疫浸润影响肿瘤预后，最后提出待研究的主题。

LAYN expression is a specific signature present in colorectal cancer (CRC) and non-small cell lung changer (NSCLC) infiltrating regulatory T lymphocytes (Treg) from CRC and NSCLC patient samples. In addition, high LAYN expression was related to poor prognosis in CRC and NSCLC patients (18). A previous study (19) further found the LAYN is a crucial gene involved in liver cancer tumor-infiltrating lymphocytes. Single-cell RNA sequencing of T cells confirmed that LAYN was up regulated in activated CD8+ T and Treg cells and represses CD8+ T cell functions in vitro. These findings suggest that LAYN has multifaceted functional roles in Treg cells and tumorinfiltrating lymphocytes. However, the underlying functions and mechanisms of LAYN in tumor progression and tumor immunology is still unclear.

第四段，解决问题。三句式，很经典的格式。

In this present study, we comprehensively analyzed LAYN expression and correlation with prognosis of cancer patients in databases such as Oncomine, PrognoScan, and Kaplan-Meier plotter（预后分析）. Moreover, we investigated the correlation of LAYN with tumor-infiltrating immune cells in the different tumor microenvironments via Tumor Immune Estimation Resource (TIMER) （免疫浸润分析）. The findings in this report shed light on the important role of LAYN in colorectal and gastric cancers as well as provide a potential relationship and an underlying mechanism between LAYN and tumor-immune interactions. （结论）。

写作举例--生信论文37--肺癌、卵巢癌和胃癌。

第一段，介绍实体瘤的背景，引出肺癌、卵巢癌和胃癌，并引出免疫治疗和存在问题；接着，用 moreover引出免疫浸润，最后总结出研究的紧迫性。

Solid tumors are the most extensive and common malignant tumors worldwide, including lung tumors, ovarian tumors, and gastric tumors. Insidious onset, invasive and fast growth, and high recurrence and metastasis rates are common characteristics leading to poor prognosis [1]（肿瘤背景介绍）. Recently, immunotherapy has been widely used in the treatment of solid tumors, including melanoma and lung, ovarian, breast, and stomach cancers, and its tolerable toxicity and long-term survival improvement have benefited many advanced cancer patients, leaving immunotherapy as the most promising direction for curing cancer [2]. Some immunotherapies, such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors or cytotoxic T lymphocyte-associated antigen 4 (CTLA4) therapies, have shown an optimistic antitumor effect in melanoma [3, 4], lung cancer [5], gastrointestinal cancer [6] and ovarian cancer [7]（免疫治疗）. However, the current anti-CTLA-4 agent showed no effect in a clinical study of prostate cancer [8], and anti-PD1 therapy showed less effect in colorectal cancer [9] and even promoted tumor progression for some patients with murine double minute2 (MDM2) amplification or epidermal growth factor receptor (EGFR) aberration [10].（存在问题） Moreover, increasing evidence has demonstrated that tumor-infiltrating immune cells interact with tumor cells and immunotherapy and have important implications for efficacy and patient outcomes [11–13]. Therefore, the elucidation of the mechanism of the interaction between tumor phenotype and infiltrating immune cells in the microenvironment and the exploration of new immune-related therapeutic targets are urgent for the treatment of solid tumors.

第二段介绍PTGIS基因的背景，包括发现历史（不重要）和功能（最重要），最终引出该基因与肿瘤的相关性（蓝色），并用一系列前人研究来论证。

Prostaglandin I2 synthase (PTGIS) is a proteinencoding gene localized on chromosome 20q13.11-q13.13 and was first reported in 1996 [14]. PTGIS encodes a member of the cytochrome P450 superfamily, a monooxygenase that catalyzes the metabolism of many drugs and the synthesis of lipids such as cholesterol and steroids. In addition, PTGIS could be involved in iron and heme metabolism, oxidative stress, xenobiotic and drug metabolism, glutathione and prostaglandin metabolism, and the conversion of prostaglandin H2 to prostaglandin I2 (PGI2) [14, 15]. A previous study observed that hypermethylation of the PTGIS promotor was associated with diminished gene expression in colorectal carcinogenesis [16]. Furthermore, other studies suggested that PTGIS variants may affect breast cancer susceptibility [17], and elevated PTGIS was associated with liver metastasis and poor survival outcomes for patients with colon cancer [18]. These findings suggest that PTGIS has distinctly essential impacts on tumorigenesis, progression, and metastasis.

第三段，介绍两者关系，提出问题。作者通过前人研究阐释PTGIS通过免疫浸润影响肿瘤预后的潜在可能性，最后提出待研究的主题（蓝色）。

PGI2 is an important product of the arachidonic acid (AA) metabolism pathway, and PTGIS is one of the key enzymes. PGI2 is involved in inflammatory responses and activation of CD4+ T cells during physiological processes [19]. In addition, PGI2 is a crucial immunoregulatory lipid mediator that affects the differentiation of Th17 cells and T-regulatory cells (Tregs) [20]. The above results suggest that PTGIS has an indirect regulatory effect on microenvironment immune cells. Nevertheless, the potential functions and mechanisms of PTGIS in tumorigenesis and development and the immune microenvironment are undefined.

第四段，解决问题。简单扼要地总结。

In this study, our aim was to comprehensively analyze the relationship between the expression of PTGIS and prognosis in cancer patients (差异分析) and to explore the correlation between PTGIS (临床意义) and tumor-infiltrating immune cells (免疫浸润分析). Our findings provide new ideas for elucidating the potential mechanism of PTGIS in tumor progression and the mechanism by which PTGIS is associated with tumor-infiltrating immune cells.

总结生信论文36、37，作者均采用第二套思路进行引文的写作。从疾病入手，即从待研究的肿瘤说起，再介绍该肿瘤的发病率、死亡率、预后和治疗情况，从而提出科学问题，引出待研究的基因；接着介绍基因的基本信息，阐释其功能，归纳式提出该基因在肿瘤中的潜在作用。而且，存在很多共同的地方。愿果友们尽快完成引文的写作。